

August 2020

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Evidence Synthesis Program (ESP) Center

Portland VA Medical Center

Portland, OR 

Devan Kansagara, MD, MCR, Director 

Chronic Pain in Veterans and 

Servicemembers with a History 

of Mild Traumatic Brain Injury: 

A Systematic Review

Authors: 

Principal Investigator: 

Maya E. O’Neil, PhD 

Kathleen F. Carlson, PhD 

Co-Investigators: 

Haley K. Holmer, PhD 

Chelsea K. Ayers, MPH

Benjamin J. Morasco, PhD

Devan Kansagara, MD, MCR

Karli Kondo, PhD 

Evidence Synthesis Program


Chronic Pain and mTBI Evidence Synthesis Program

i

PREFACE

The VA Evidence Synthesis Program (ESP) was established in 2007 to provide timely and 

accurate syntheses of targeted healthcare topics of importance to clinicians, managers, and 

policymakers as they work to improve the health and healthcare of Veterans. These reports help: 

• Develop clinical policies informed by evidence;

• Implement effective services to improve patient outcomes and to support VA clinical 

practice guidelines and performance measures; and 

• Set the direction for future research to address gaps in clinical knowledge.

The program is comprised of three ESP Centers across the US and a Coordinating Center located 

in Portland, Oregon. Center Directors are VA clinicians and recognized leaders in the field of 

evidence synthesis with close ties to the AHRQ Evidence-based Practice Center Program and 

Cochrane Collaboration. The Coordinating Center was created to manage program operations, 

ensure methodological consistency and quality of products, and interface with stakeholders. To 

ensure responsiveness to the needs of decision-makers, the program is governed by a Steering 

Committee comprised of health system leadership and researchers. The program solicits 

nominations for review topics several times a year via the program website. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, Deputy 

Director, ESP Coordinating Center at Nicole.Floyd@va.gov.

Recommended citation: O’Neil ME, Carlson KF, Holmer HK, Ayers CK, Morasco BJ, 

Kansagara D, Kondo K. Chronic Pain in Veterans and Servicemembers with a History of Mild 

Traumatic Brain Injury: A Systematic Review. Washington, DC: Evidence Synthesis Program, 

Health Services Research and Development Service, Office of Research and Development, 

Department of Veterans Affairs. VA ESP Project #05-225; 2020. Available at: 

https://www.hsrd.research.va.gov/publications/esp/reports.cfm. 

This report is based on research conducted by the Evidence Synthesis Program (ESP) Center located at 

the VA Portland Healthcare System, Portland, OR, funded by the Department of Veterans Affairs, Veterans 

Health Administration, Health Services Research and Development. The findings and conclusions in this 

document are those of the author(s) who are responsible for its contents; the findings and conclusions do 

not necessarily represent the views of the Department of Veterans Affairs or the United States government. 

Therefore, no statement in this article should be construed as an official position of the Department of 

Veterans Affairs. No investigators have any affiliations or financial involvement (eg, employment, 

consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or 

pending, or royalties) that conflict with material presented in the report.
Chronic Pain and mTBI Evidence Synthesis Program

ii

ACKNOWLEDGMENTS 

This topic was developed in response to a nomination by the VHA Committee on the Care of 

Veterans with Traumatic Brain Injury (TBI) for an evidence review on the epidemiology, 

assessment, and treatment of chronic pain complicated by co-occurring mild traumatic brain 

injury (mTBI) in combat veterans. The scope was further developed with input from the topic 

nominators (ie, Operational Partners), the ESP Coordinating Center, the review team, and the 

technical expert panel (TEP).

In designing the study questions and methodology at the outset of this report, the ESP consulted 

several technical and content experts. Broad expertise and perspectives were sought. Divergent 

and conflicting opinions are common and perceived as healthy scientific discourse that results in 

a thoughtful, relevant systematic review. Therefore, in the end, study questions, design,

methodologic approaches, and/or conclusions do not necessarily represent the views of 

individual technical and content experts. 

The authors gratefully acknowledge Robin Paynter, MLIS, and the following individuals for 

their contributions to this project: 

Operational Partners

Operational partners are system-level stakeholders who have requested the report to inform 

decision-making. They recommend Technical Expert Panel (TEP) participants; assure VA 

relevance; help develop and approve final project scope and timeframe for completion; provide 

feedback on draft report; and provide consultation on strategies for dissemination of the report to 

field and relevant groups.

Stuart Hoffman, PhD 

Scientific Program Manager, VA Office of Research and Development 

Veterans Health Administration, Washington, DC

Ralph DePalma, MD, FACS 

Special Operations Officer, VA Office of Research and Development 

Veterans Health Administration, Washington, DC

Audrey Kusiak, PhD 

Scientific Program Manager, VA Office of Research and Development 

Veterans Health Administration, Washington, DC

David Cifu, MD 

Senior TBI Specialist, VA Office of Research and Development 

Veterans Health Administration, Washington, DC

Technical Expert Panel (TEP)

To ensure robust, scientifically relevant work, the TEP guides topic refinement; provides input 

on key questions and eligibility criteria, advising on substantive issues or possibly overlooked 
Chronic Pain and mTBI Evidence Synthesis Program

iii

areas of research; assures VA relevance; and provides feedback on work in progress. TEP 

members are listed below: 

Friedhelm Sandbrink, MD 

George Washington University & VA Central Office 

Washington, DC 

Joel Scholten, MD 

Georgetown University & VA Central Office

Washington, DC 

Linda Picon, MCD, CCC-SLP

VA Central Office

Washington, DC 

Lisa Brenner, PhD, ABPP 

VA Eastern Colorado Health Care System

Aurora, CO 

Mary Jo Pugh, PhD, RN 

The University of Utah School of Medicine & Salt Lake City VA Health Care System

Salt Lake City, UT 

Erin Krebs, MD, MPH 

University of Minnesota & Minneapolis VA Health Care System

Minneapolis, MN 

Robert Kerns, PhD 

Yale University 

New Haven, CT

Jason Sico, MD, MHS

Yale School of Medicine & VA Connecticut Healthcare System

New Haven, CT

Peer Reviewers

The Coordinating Center sought input from external peer reviewers to review the draft report and 

provide feedback on the objectives, scope, methods used, perception of bias, and omitted 

evidence. Peer reviewers must disclose any relevant financial or non-financial conflicts of 

interest. Because of their unique clinical or content expertise, individuals with potential conflicts 

may be retained. The Coordinating Center and the ESP Center work to balance, manage, or 

mitigate any potential nonfinancial conflicts of interest identified. 
Chronic Pain and mTBI Evidence Synthesis Program

iv

TABLE OF CONTENTS 

PREFACE ....................................................................................................................................... I

ACKNOWLEDGMENTS ........................................................................................................... II

ABSTRACT ................................................................................................................................... 1

EXECUTIVE SUMMARY .......................................................................................................... 2

Aim ............................................................................................................................................. 2

Methods....................................................................................................................................... 2

Results ......................................................................................................................................... 3

Figure i. Number of studies reporting prevalence of chronic pain in Veterans/Servicemembers 

with histoy of mTBI, by pain type .............................................................................................. 3

Figure ii. Range of chronic pain prevalence estimates by pain type across studies ................... 5

Conclusion .................................................................................................................................. 9

Abbreviations Table .................................................................................................................. 10

EVIDENCE REPORT ................................................................................................................ 13

INTRODUCTION....................................................................................................................... 13

METHODS .................................................................................................................................. 15

Topic Development ................................................................................................................... 15

Search Strategy ......................................................................................................................... 16

Study Selection ......................................................................................................................... 16

Data Abstraction ....................................................................................................................... 20

Quality Assessment ................................................................................................................... 20

Data Synthesis ........................................................................................................................... 20

Rating the Body of Evidence .................................................................................................... 20

RESULTS .................................................................................................................................... 22

Key Question 1: What is the prevalence of chronic pain in US Veterans or Servicemembers 

with a history of mTBI? ............................................................................................................ 24

Summary of Findings ............................................................................................................ 24

Detailed Results .................................................................................................................... 38

Key Question 2: What is the risk of suicide in US Veterans or Servicemembers with chronic 

pain and a history of mTBI? ..................................................................................................... 63

Summary of Findings ............................................................................................................ 63
Chronic Pain and mTBI Evidence Synthesis Program

v

Key Question 3. What are the benefits and harms of interventions to treat chronic pain in 

Veterans or Servicemembers with a history of mTBI? ............................................................. 64

Summary of Findings ............................................................................................................ 64

Detailed Results .................................................................................................................... 64

DISCUSSION .............................................................................................................................. 71

Conclusion ................................................................................................................................ 78

REFERENCES ............................................................................................................................ 80

TABLES

Table 1. PICOTS by Key Question ........................................................................................... 18

Table 2. Characteristics of studies reporting prevalence of chronic pain in 

Veterans/Servicemembers with a history of mTBI ................................................................... 25

Table 3. Prevalence estimates of general chronic pain from studies of 

Veterans/Servicemembers with a history of mTBI ................................................................... 39

Table 4. Prevalence estimates of head pain from studies of Veterans/Servicemembers with a 

history of mTBI......................................................................................................................... 42

Table 5. Prevalence estimates of other chronic pain from studies of Veterans and 

Servicemembers with a history of mTBI .................................................................................. 49

Table 6. Prevalence of Chronic Pain in Veterans and Servicemembers with a History of mTBI 

by mTBI Etiology ..................................................................................................................... 57

Table 7. Characteristics of studies of interventions for headaches in participants with a history 

of mTBI ..................................................................................................................................... 65

Table 8. Findings of studies of interventions for headaches in participants with a history of 

mTBI ......................................................................................................................................... 68

Table 9. Risk of bias in trials of interventions for chronic pain in Veterans with a history of 

mTBI ......................................................................................................................................... 70

Table 10. Criteria used in quality assessment of randomized controlled trials ........................ 93

Table 11. Quality ratings for studies reporting prevalence of chronic pain in 

Veterans/Servicemembers with history of mild traumatic brain injury .................................... 94

FIGURES

Figure 1. Analytic Framework .................................................................................................. 16

Figure 2. Literature Flow Chart ................................................................................................ 23

Figure 3. Prevalence of general chronic pain in Veterans/Servicemembers with a history of 

mTBI by study and pain measurement tool .............................................................................. 60
Chronic Pain and mTBI Evidence Synthesis Program

vi

Figure 4. Prevalence of head pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool .............................................................................................. 61

Figure 5. Prevalence of back pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool .............................................................................................. 62

Figure 6. Prevalence of neck pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool .............................................................................................. 62

Figure 7. Prevalence of arm, leg, and/or joint pain in Veterans and Servicemembers with a 

history of mTBI by study and pain measurement tool .............................................................. 63

Figure 8. Number of studies reporting prevalence of chronic pain in Veterans and 

Servicemembers with mTBI by pain type ................................................................................ 71

Figure 9. Range of chronic pain prevalence estimates by pain type across studies .................. 73

APPENDIX A. SEARCH STRATEGIES ................................................................................. 85

APPENDIX B. STUDY SELECTION ...................................................................................... 91

APPENDIX C. QUALITY ASSESSMENT .............................................................................. 93

APPENDIX D. STUDIES EXCLUDED AT FULL TEXT LEVEL ....................................... 99

APPENDIX E. PEER REVIEW COMMENTS/AUTHOR RESPONSES .......................... 111
Chronic Pain and mTBI Evidence Synthesis Program

1

ABSTRACT

Aim: We conducted a systematic review on the prevalence of chronic pain in Veterans and 

Servicemembers (SMs) with a history of mild traumatic brain injury (mTBI), the risk of suicide, 

and the benefits and harms of interventions to treat chronic pain in this population. 

Methods: We searched electronic databases, clinical trial registries, and reference lists through 

February 2020. For intervention studies, we included only randomized and non-randomized 

controlled trials. We abstracted study design, sample size, setting, population characteristics, 

inclusion and exclusion criteria, operationalizations of key variables, and results. Independent 

dual assessment of study’s full text and quality ratings were agreed upon by consensus using prespecified criteria. 

Results: 27 articles (26 studies) reported chronic pain prevalence estimates, 1 study examined 

suicide outcomes, and 3 studies examined interventions for the treatment of chronic pain in 

Veterans and SMs with a history of mTBI. Across studies, the prevalence of chronic pain among 

this population varied widely but, overall, was high. Head pain (ie, headaches or migraines; 23 

studies) was the most common, followed by back (10), and arm, leg, and/or joint pain (9). Four 

articles reported the use of pain medication as an indicator of chronic pain. The 1 study 

examining suicide outcomes found that compared to those with relatively low rates of pain and 

other sensory diagnoses, Veterans with high post-concussive symptoms, and mental health and 

pain comorbidities were more likely to have been diagnosed with suicidal ideation or attempt. 

The 3 intervention studies were small and provide insufficient evidence for rTMS (2 RCTs) and 

Flexyx Neurotherapy System, a type of neurotherapy. 

Conclusion: Chronic pain in Veterans and SMs with a history of mTBI is common. Precise 

prevalence estimates are hampered by heterogeneity. There is very little current research of 

suicide-related outcomes in, and interventions for, this population. More research is needed. 
Chronic Pain and mTBI Evidence Synthesis Program

2

EXECUTIVE SUMMARY 

AIM

We conducted a systematic review to synthesize the existing literature on the prevalence of 

chronic pain in Veterans and Servicemembers (SMs) with a history of mild traumatic brain 

injury (mTBI), the risk of suicide in this population, and the benefits and harms of interventions 

to treat chronic pain in this population. 

METHODS

We searched electronic databases (Ovid Medline; Ovid EBM Reviews: Cochrane Central 

Register of Controlled Trials, Cochrane Database of Systematic Reviews; Ovid PsycINFO; 

CINAHL; Scopus; Google Scholar; and Epistemonikos), clinical trial registries, and reference 

lists from database inception through February 7, 2020 for studies providing prevalence 

estimates of chronic pain in US Veterans or SMs with a history of mTBI, reporting estimates of 

suicide risk among US Veterans or SMs with a history of mTBI and chronic pain, or examining 

treatment interventions for chronic pain in Veterans or SMs with a history of mTBI from any 

country. For intervention studies, we included only randomized and non-randomized controlled 

trials.

Chronic pain is commonly defined as pain lasting or recurring for more than 3 months,1

 though 

definitions vary across published studies. In order to provide a comprehensive overview of this 

body of literature, we considered any pain measure that was not clearly described as measuring 

acute pain to be chronic pain (eg, pain over past 30 days, headaches, etc), along with proxies for

measures of chronic pain such as diagnosis codes in healthcare records, analgesic medication 

use, and conditions usually accompanied by chronic pain (eg, arthritis). We included prevalence 

estimates for these definitions of chronic pain from any US Veteran or SM study population that 

was explicitly defined as having a history of mTBI, distinct from TBI of greater severity. Mild 

TBI was defined as an external force to the head followed by ≤30 minutes of loss of 

consciousness, 0-1 days of posttraumatic amnesia, or up to 24 hours of altered mental status, 

along with normal structural imaging if completed.

2

 We excluded studies that reported results for 

populations with mixed TBI severity (eg, mild plus moderate and/or severe TBI). For each key 

question of interest, we used a “best evidence” approach to guide additional study design criteria 

depending on the question under consideration and the literature available. 

For all studies we abstracted study design, sample size, setting, population characteristics, 

participant inclusion and exclusion criteria, definitions/operationalizations of key variables, and 

results. If data were presented for non-mTBI comparison groups, these were also abstracted. For 

intervention studies, we also abstracted intervention and comparator characteristics including 

dosage, timing, and duration of treatment, duration of follow-up, adjunctive interventions (if 

applicable), and behavioral and health outcomes, as well as relevant harms. Two reviewers 

independently assessed the methodological quality of each study using established methods for 

each study design. Strength of evidence for intervention studies was determined by consensus. 
Chronic Pain and mTBI Evidence Synthesis Program

3

RESULTS

We identified 27 articles (representing 26 studies) reporting chronic pain prevalence estimates in 

US Veterans and SMs with a history of mTBI, 1 study examining suicide outcomes in US 

Veterans and SMs with a history of mTBI, and 3 studies examining interventions for the 

treatment of chronic pain in Veterans and SMs with a history of mTBI from any country. 

Key Question 1: What is the prevalence of chronic pain in US Veterans or 

Servicemembers with a history of mTBI?

Included prevalence studies describe a wide range of chronic pain types, with the most common 

being head pain (ie, headaches or migraines, 23 studies), followed by back pain (10 studies), and 

arm, leg, and/or joint pain (9 studies). Four articles reported the use of pain medication (eg, 

analgesics including opioids) as an indicator of chronic pain (see Figure i). Across studies there 

was substantial heterogeneity in sample size (ie, 40 to 102,055 Veterans or SMs with history of 

mTBI), population (eg, Veterans, SMs, or both; era of service; geographic region; comorbid 

conditions; and combat exposure), time since mTBI, and length of follow-up, as well as the 

methods used to identify, define, and operationalize both mTBI and chronic pain. 

Figure i. Number of studies reporting prevalence of chronic pain in 

Veterans/Servicemembers with histoy of mTBI, by pain type

Note. Some studies reported multiple pain types.
Chronic Pain and mTBI Evidence Synthesis Program

4

Across these studies, the prevalence of chronic pain among Veterans and SMs varied widely but, 

overall, was high. As expected in this population, prevalence estimates of head pain and chronic 

pain generally were higher than estimates of other specific chronic pain conditions (eg, chest

pain, abdominal/stomach pain). However, across studies, there were wide ranges of prevalence 

estimates for each pain type, likely due to the varying study designs, target populations or 

samples, pain definitions, operationalization of key variables, and pain ascertainment periods 

(see Figure ii). This heterogeneity across studies limits the conclusions that can be drawn about 

the frequency of pain or the most common pain types among Veterans and SMs who have 

experienced mTBI. However, when studies presented pain prevalence data for comparison 

groups without mTBI, they were consistently lower across all pain types.
Chronic Pain and mTBI Evidence Synthesis Program

5

Figure ii. Range of chronic pain prevalence estimates by pain type across studies
Chronic Pain and mTBI Evidence Synthesis Program

6

Although the wide variation in estimates is not surprising given the heterogeneity across studies, 

these findings, or rather the lack of concrete findings, highlight a need to establish and 

implement consistent methods to assess pain conditions that are prevalent in US Veteran and SM

populations. Studies are needed to assess the prevalence of chronic pain among all US Veterans 

and SMs with a history of mTBI (rather than, for example, treatment-seeking Veterans 

specifically) and to compare the prevalence levels of pain types by important Veteran and SM 

characteristics, including service history, physical and mental health comorbidities, and 

healthcare utilization patterns. Additionally, despite being beyond the scope of this review, we 

noted that few studies compared pain prevalence between those with and without mTBI and, 

thus, it remains unclear how pain conditions are associated with mTBI (ie, whether they tend to 

be more commonly diagnosed among treatment-seeking samples, whether they are a result of the 

mTBI itself, or whether they are a result of the same characteristics and exposures that led to 

mTBI). To answer these questions and maximize usefulness of the evidence, studies that 

randomly sample Veterans and SMs, follow them over time, and use established and consistent 

definitions and operationalizations of mTBI and pain are needed.

Similarly, although we found well-conducted studies of treatment-seeking samples of Veterans 

and SMs that reported on chronic pain among those with mTBI, these studies by nature relied on 

selective (ie, non-random) samples and/or proxy measures of mTBI and pain such as 

International Classification of Diseases (ICD) diagnosis codes. To better understand the 

prevalence of chronic pain conditions and, in particular, to anticipate treatment needs among 

Veterans and SMs who utilize the VA or Military Health System, random or otherwise 

representative samples of individuals with (and, for comparison, without) mTBI should be 

assessed using established and consistent chronic pain definitions and measures.

For this review, we chose to include studies of chronic pain even if the study did not include a 

rigorous assessment to determine the chronicity or severity of pain symptoms. For example, we 

included studies where pain symptoms were assessed only for the past month. While this 

methodology could result in over-estimation of the prevalence of chronic pain, we opted to 

include these studies in order to generate a fuller picture of the problem of pain among Veterans 

and SMs with a history of mTBI. Future research that aims to understand chronic pain in a 

sample of all Veterans/SMs with mTBI history, or of specified treatment-seeking Veterans/SMs 

with mTBI history, would benefit from the assessment of pain chronicity (at least 3-6 months) 

and severity (moderate or higher). There are also recommended strategies for assessing chronic 

pain using administrative data, such as ICD diagnosis codes, that can improve the accuracy and 

comparability of prevalence estimates in these types of studies of chronic pain.3

For general chronic pain among Veterans with a history of mTBI, we identified a relatively 

robust prevalence estimate of 59% from Seal et al.

4 This estimate was derived from a large 

database of Post-9/11 Veterans who completed a Comprehensive TBI Evaluation (CTBIE) in the 

VA healthcare system and, thus, represents a relatively large target population. However, 

Veterans who complete the CTBIE are generally seeking treatment for a variety of postdeployment health symptoms that may or may not be related to mTBI, or pain. The CTBIE is a 

standardized and templated clinical assessment completed by a specialty provider and includes 

standardized assessments of pain; however, patients who complete the CTBIE may not need

pain-related care (ie, are not bothered by pain). When CTBIE data or pain diagnosis codes are 

used to estimate chronic pain, as in the case of this study, the true prevalence of chronic pain 
Chronic Pain and mTBI Evidence Synthesis Program

7

may be over- or underestimated. Most other studies examining general chronic pain included 

fewer than 500 participants and used varied methods to identify chronic pain. The only other 

large study utilized VA electronic health record (EHR) data and reported pain diagnoses in 82% 

of Veterans with diagnosed mTBI and comorbid posttraumatic stress disorder (PTSD), and 71% 

among those with mTBI but no PTSD diagnosis. This study identified mTBI and chronic pain by 

the presence of ICD diagnosis codes in EHR data and may over- (or even under-) estimate their 

prevalence due to this approach.

3,5 Studies of pain disability/interference (defined as moderateto-severe interference in daily functioning) due to chronic pain were fairly consistent, with

estimates of 70-75%. Studies of pain severity, based on self-report using Likert-like scales,

indicated that roughly half of Veterans and SMs with a history of mTBI reported moderate to 

severe pain, and studies that examined pain frequency reported that about one-third to one-half 

experience pain more than 15 days per month. 

Head pain such as headaches and migraines was the most studied chronic pain type (23 studies), 

with prevalence estimates ranging widely from 3% to 98%. Relatively robust (but still widely 

varied) estimates come from 5 large studies, all of which used EHR or CTBIE data and thus may 

not represent the true prevalence of head pain across the population of Veterans or SMs with 

mTBI history. Among these 5 studies, prevalence estimates of headache or migraines from 4 

studies of Post-9/11 Veterans with a history of mTBI ranged from 20% to 94% (this latter study 

reported data from a CTBIE item assessing the presence of any headaches), and 1 study of SMs 

reported headache prevalence estimate of 15.2%. Prevalence estimates appear to vary by target 

population (Veteran versus SM; healthcare utilization), time since mTBI, length of follow-up, 

method of identifying and classifying chronic pain (and mTBI), and data source. Many of the 

studies examined EHR data that include all Veterans or SMs with mTBI and chronic pain-related 

ICD codes. Other studies, including those of the large cohort of Veterans who completed the 

CTBIE, were of treatment-seeking populations, which would be expected to have higher pain

prevalence. This difference alone may account for much of the variance between studies. The 

prevalence estimates of moderate to severe pain, and frequent pain, also varied widely. 

Prevalence estimates for back pain were largely consistent, falling between 32% and 44% for 

SMs in 3 studies using the 15-item Patient Health Questionnaire (PHQ-15), and 13%-15% for 

upper back and 53%-58% for lower back pain among Veterans who completed the CTBIE. 

There was wide variation in the prevalence estimates of neck pain in Veterans with a history of 

mTBI. The 2 largest studies reported prevalence estimates of 6% (VA EHR data) and 23% 

(CTBIE). With the exception of arthritis (41.1% to 51%), the prevalence estimates of other pain 

types were relatively low.

Four articles reported on pain medication use which we abstracted as a proxy measure for 

chronic pain. Of these, 2 relatively small studies specifically looked at opioid medication use for 

pain. Estimates of prevalence of opioid use among Veterans with a history of mTBI from these 

studies were 12% and 49%; these differences were likely due to the different data sources, 

populations, and timing of measurements used in these studies. 

Three studies compared the prevalence of chronic pain in Veterans and SMs with a history of 

mTBI by mTBI etiology. These studies compared chronic pain prevalence among individuals 

who experienced mTBI from blast versus non-blast sources; no studies were identified that 

compared pain prevalence levels by other etiologies. Overall, in the 3 studies identified, blast-
Chronic Pain and mTBI Evidence Synthesis Program

8

related mTBI did not appear to be associated with more frequent and more severe pain. 

However, 1 study reported that, among Veterans who experienced loss of consciousness (LOC) 

after their mTBI, those with blast-related mTBI had a significantly higher prevalence of head 

pain than those with non-blast-related mTBI (40% versus 23%). None of the other pain types 

assessed in this study differed by mTBI etiology. None of the studies examined or compared pain 

prevalence by location of mTBI, location of co-occurring injuries, or timing of pain onset 

relative to the mTBI.

Results of studies examining pain assessment methods suggest that different types of pain 

measures were associated with higher or lower pain prevalence estimates. In addition to pain 

assessment methods, other aspects of study design likely influenced prevalence estimates as well. 

For example, studies of specialized clinics designed to treat a particular condition would be 

expected to have higher rates of that condition (such as in the study by Ruff et al,6 of a small 

sample seen in a polytrauma clinic) than studies examining the prevalence in a broad, full, or 

“all-comers” population (such as in studies examining all post-deployment Veterans/SMs or 

identifying pain diagnoses in the EHR). 

Key Question 2: What is the risk of suicide in US Veterans or Servicemembers 

with chronic pain and a history of mTBI?

We found only a single study examining suicide-related outcomes in US Veterans and SMs with 

both chronic pain and a history of mTBI. The study used VA EHR data and categorized Veterans 

with and without a history of mTBI into trajectory groups based on an algorithm using ICD

diagnosis codes. As compared to those with relatively low rates of mental health, pain, and other 

sensory diagnoses during the trajectory development period, Veterans with high mental health, 

post-concussive symptoms, and pain comorbidities were significantly more likely to have been 

diagnosed with suicidal ideation or attempt during the follow-up period.

7 This study compared 

the prevalence of suicide-related behaviors between those with and without a history of mTBI 

(eg, 6.6% versus 2.4%, respectively) but did not likewise directly compare suicide-related 

behaviors between those with mTBI with and without comorbid pain. However, considering the 

persistently high rates of suicide in Veteran populations,8,9 and higher rates of suicide and other 

causes of mortality among Veterans with a history of mTBI compared to those without,10,11 more 

research of this particularly vulnerable population is needed. 

Key Question 3. What are the benefits and harms of interventions to treat chronic 

pain in Veterans or Servicemembers with a history of mTBI?

Although chronic pain is well established as a common comorbidity among Veterans and SMs 

with a history of mTBI, we found very few trials of interventions to treat chronic pain in this 

population, even when searching for studies from any country. The 3 studies that met inclusion 

criteria were small and provide insufficient-strength evidence supporting the interventions 

studied (repetitive Transcranial Magnetic Stimulation [rTMS] in 2 RCTs and Flexyx 

Neurotherapy System [FNS], a type of neurotherapy, in 1 small pre-post trial). All 3 studies 

targeted chronic headaches, and none assessed nor treated other types of chronic pain.12-14 Also 

notable is that no studies compared the efficacy of chronic pain treatments among those with, 

versus without, mTBI. This review was limited to chronic pain treatment trials of Veterans and 

SMs with a history of mTBI from any country because of the unique military-related 

circumstances (eg, blast exposure) that can contribute to pain in this population. However, due to 
Chronic Pain and mTBI Evidence Synthesis Program

9

the very small number of trials specific to this population, future efforts should consider results 

from pain interventions among broader populations (eg, adult civilians) or Veterans and SMs 

without a history of mTBI when making treatment, policy, or research scoping decisions.

CONCLUSION

Chronic pain, particularly head and back pain, is common among US Veterans and SMs with a 

history of mTBI, as is the use of medications indicative of pain conditions, such as prescription 

opioids. In studies providing comparisons, pain prevalence estimates are consistently higher 

among those with, versus without, mTBI history, and for those with comorbid mTBI and PTSD 

compared to those with mTBI but no PTSD. Based on the existing research, precise estimates of 

the prevalence of pain conditions, locations, disability/interference, and severity are hampered by 

heterogeneity in study populations/samples, timing of pain ascertainment relative to individuals’ 

mTBI history, duration of study follow-up, and methods used to identify, define, and 

operationalize both mTBI and chronic pain. Additionally, only a single study examined the risk 

of suicide, and only 3 trials of interventions to treat chronic pain in this complex population were 

identified. Thus, the prevalence of chronic pain in the general population of US Veterans and 

SMs, the impact of comorbid pain and mTBI on suicide risk in this population, and the efficacy 

of pain therapies among those with comorbid mTBI and chronic pain remain largely unknown.

Research studies specifically designed with the intent of filling these knowledge gaps are needed 

to inform current and future service needs for this population. Given the high prevalence of 

mTBI history in Veterans and SMs, and the importance of meeting the social and clinical needs 

of this large population, this research is urgent and essential.
Chronic Pain and mTBI Evidence Synthesis Program

10

ABBREVIATIONS TABLE

Abbreviation Definition

AA African-American

AE Adverse Event

ANOVA Analysis of Variance

AOC Alteration of Consciousness

CA California

CDC Centers for Disease Control and Prevention

CDH Chronic Daily Headaches

CDP-SOT Computerized Dynamic Posturography Sensory Organization Test

CDSR Cochrane Database of Systematic Reviews

CENC Chronic Effects of Neurotrauma Consortium

CI Confidence Interval

CO Colorado

CoE Center of Excellence

CP Chronic pain

CTBIE Comprehensive TBI Evaluation

DMDC Defense Manpower Data Center

DMSS Defense Medical Surveillance System

DoD Department of Defense

DVBIC Defense and Veterans Brain Injury Center

EBM Evidence-Based Medicine

EEG Electroencephalogram

EHR Electronic Health Record

EM Electromagnetic Energy

ESP Evidence Synthesis Program

EQ-5D-5L EuroQol Group 5-Dimension 5-Level version

FH Frequent Headaches

FL Florida

FNS Flexyx Neurotherapy System

FY Fiscal year

GCS Glasgow Coma Scale

HI Hawaii

HIT-6 6-item Headache Impact Test

ICD International Classification of Diseases

ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification

ICDH-2 International Classification of Headache Disorders 2nd edition

ICDH-3 International Classification of Headache Disorders 3rd edition

ISS Injury Severity Scale

KQ Key Question

LOC Loss of Consciousness

MA Meta-Analysis
Chronic Pain and mTBI Evidence Synthesis Program

11

Abbreviation Definition

MD Mean Difference

mTBI Mild Traumatic Brain Injury

MINI Mini-International Neuropsychiatric Interview

M-VAS Mechanical Visual Analog Scale

NA Native American

NC North Carolina

NR Not Reported

NRCT Non-Randomized controlled trial

NRS Numerical Rating Scale

NS Not Significant

NSI Neurobehavioral Symptom Inventory

OEF Operation Enduring Freedom

OH Ohio

OIF Operation Iraqi Freedom

OND Operation New Dawn

OSU TBI-ID Ohio State University Traumatic Brain Injury Identification Method

P P-value

PCE Potential Concussive Event

PCL-17 17-item Posttraumatic Stress Disorder Checklist

PDHA Post-Deployment Health Assessment

PDHRA Post-Deployment Health Re-Assessment

PHQ-15 15-item Patient Health Questionnaire 

PHQ-9 9-item Patient Health Questionnaire 

PICOTS Population, Interventions, Comparators, Outcomes, Timing, Setting, and Study Design

PNS Polytrauma Network Site

PPCS Persistent Post-Concussive Symptoms

PTA Posttraumatic Amnesia

pts Participants

PTSD Posttraumatic Stress Disorder

QOL Quality of Life

RCT Randomized Controlled Trial

RoB Risk of Bias

RR Relative Risk

rTMS Repetitive Transcranial Magnetic Stimulation

Rx Prescription Medication

SAE Serious Adverse Event

SD Standard Deviation

SE Standard Error

SM Servicemember

SMD Standard Mean Difference

SOE Strength of Evidence

SR Systematic Review
Chronic Pain and mTBI Evidence Synthesis Program

12

Abbreviation Definition

SRB Suicide Related Behavior

TBI Traumatic Brain Injury

TBIMS Traumatic Brain Injury Model Systems

TEP Technical Expert Panel

TMS Transcranial Magnetic Stimulation

TRACTS Translational Research Center for TBI and Stress Related Disorders

TX Texas

US United States 

VA Veterans Affairs; or Virginia

VALOR Veterans' After-discharge Longitudinal Registry

VAMC Veterans Affairs Medical Center

VCU-rCDI Virginia Commonwealth University retrospective Concussion Diagnostic Interview

VHA Veterans Health Administration

WRAMC Walter Reed Army Medical Center
Chronic Pain and mTBI Evidence Synthesis Program

13

EVIDENCE REPORT

INTRODUCTION

The post-9/11 military operations in and around Afghanistan and Iraq (Operations Enduring 

Freedom, Iraqi Freedom, and New Dawn, or OEF/OIF/OND) have served to highlight the high 

prevalence of mild traumatic brain injury (mTBI) in Servicemembers (SMs) and Veterans, often 

referred to as the “signature injury” of these conflicts.15 Approximately 413,000 SMs have 

experienced a traumatic brain injury (TBI) since the year 2000, and over 80% of those were

classified as mild in severity.16

Mild TBI often resolves completely and quickly, without the need for much or any intervention. 

However, up to one-third of individuals who experience an mTBI have a longer and/or more 

severe symptom course.

17,18 It is not clear why some individuals experience long-term sequelae 

from mTBI events while others experience complete resolution.19 Among SMs and Veterans in 

particular, it is also unclear whether symptoms and sequelae that are attributed to mTBI are due 

to the mTBI itself or, rather, are physical and mental health outcomes related to the same 

exposures (ie, related to combat) that led to the mTBI. 

Regardless of the source, it is important to provide rehabilitative services to individuals with a 

history of mTBI to maximize functional outcomes.19 To meet Veterans’ needs, the Department 

of Veterans Affairs (VA) Veterans Health Administration (VHA) developed a comprehensive 

system of care to ensure that those exposed to mTBI and who may be experiencing long-term 

sequelae are referred for appropriate services. This TBI/Polytrauma System of Care involves a 

brief screen, used universally with nearly all OEF/OIF/OND Veterans, to detect potential history 

of mTBI plus current symptoms that may be related; a follow-up clinical evaluation (the 

Comprehensive TBI Evaluation, or CTBIE) with a specialist to confirm whether symptoms are 

or are not related to mTBI, and to provide referrals for related care needs; and a network of 

polytrauma providers and clinics to ensure Veterans’ TBI-related needs are met.20 The 

TBI/Polytrauma System of Care has been lauded for ensuring that Veterans with mTBI-related

symptoms and sequelae are identified and receive care that maximizes functioning and quality of 

life.21 However, the screening and evaluation program has also been criticized for causing 

inflated symptom reporting, reduced recovery expectations, and leading to other iatrogenic 

effects among Veterans who may not otherwise experience long-term effects of mTBI. 22,23 

Common sequelae and health conditions that are associated with mTBI include mental health 

concerns such as posttraumatic stress disorder (PTSD) and depression, cognitive problems, 

sensory sensitivity, and chronic pain,17,18,24 which are often associated with significant functional 

limitations. Due to the common co-occurrence of mTBI, PTSD, and chronic pain among SMs 

and Veterans, clinicians and researchers have described these comorbidities as the polytrauma 

clinical triad.25 The extent to which these comorbidities interact to further increase the risk of

functional limitations or other adverse outcomes beyond mTBI history alone is unknown, but the 

number of patients meeting the polytrauma clinical triad definition, and the potential for poor 

outcomes among these individuals, warrants close attention. While some recent clinical 

intervention research has targeted comorbid mTBI and PTSD (eg, Pagulayan et al, 201726), there 
Chronic Pain and mTBI Evidence Synthesis Program

14

is very limited research on interventions specifically targeting chronic pain among individuals 

with a history of mTBI (eg, Irvine, 201827) or targeting the triad of conditions. 

The rate of suicide among military SMs and Veterans is higher than among the general US 

population and continues to increase annually.28 Although the reasons for increased risk of 

suicide among SMs and Veterans, relative to others, are not well understood, both mTBI and 

pain have been identified as risk factors in both Veteran and non-Veteran populations.10,11,29,30

Whether or not comorbid mTBI and pain would interact to increase risk of suicide beyond the 

risk associated with either condition alone is unknown, but it stands to reason that SMs and 

Veterans with a history of both mTBI and pain are a potentially high-risk population.

Understanding this risk and developing therapies or other interventions that can reduce it, in this 

population or among SMs and Veterans more generally, is critical. 

Because these complexities and additional clinical complications may be present when mTBI 

and pain are co-occurring, there is a need to better understand both the epidemiology of these 

conditions and their potential impact on risk of suicide and suicide-related behaviors. There is 

also a need for a comprehensive understanding of the effectiveness of intervention research 

targeting chronic pain among individuals with a history of mTBI. The purpose of this systematic 

review is to address these epidemiologic and clinical research questions by identifying and 

synthesizing existing literature on mTBI and chronic pain, highlighting research gaps and future 

research needs, as well as describing evidence specifically related and relevant to Veterans and 

SMs. 
Chronic Pain and mTBI Evidence Synthesis Program

15

METHODS 

TOPIC DEVELOPMENT

This topic was nominated by the VHA Committee on the Care of Veterans with TBI. The scope 

was refined through a process that included a preliminary review of published peer-reviewed 

literature and consultations with our operational partners and a technical expert panel (TEP). Our 

approach was guided by a conceptual framework developed in consultation with our operational 

partners and TEP (Figure 1. Analytic Framework).

The Key Questions (KQs) for this systematic review were: 

KQ1: What is the prevalence of chronic pain in US Veterans or Servicemembers with a history 

of mTBI?

a. What are the most common types of chronic pain in US Veterans or Servicemembers 

with a history of mTBI?

b. Do the prevalence or types of chronic pain experienced by US Veterans or 

Servicemembers with a history of mTBI differ by mTBI etiology?

c. How do estimates of the prevalence of chronic pain and mTBI in US Veterans or 

Servicemembers differ according to pain measurement methods or definitions? 

KQ2: What is the risk of suicide in US Veterans or Servicemembers with chronic pain and a 

history of mTBI?

a. How does the prevalence of suicide-related outcomes in US Veterans or Servicemembers 

with a history of mTBI and chronic pain compare to US Veterans or Servicemembers 

with no mTBI history and/or no chronic pain? 

b. How does the prevalence of suicide-related outcomes in US Veterans or Servicemembers 

with chronic pain and history of mTBI compare to civilians with chronic pain and history 

of mTBI?

c. How does the prevalence of suicide-related outcomes in US Veterans or Servicemembers 

with chronic pain and a history of mTBI vary depending on mTBI etiology? 

d. How does the prevalence of suicide-related outcomes in US Veterans or Servicemembers 

with chronic pain and a history of mTBI vary depending on prescription opioid use or 

opioid use disorder? 

KQ3: What are the benefits and harms of interventions to treat chronic pain in Veterans or 

Servicemembers with a history of mTBI?

a. Do the benefits or harms differ by mTBI etiology, type of chronic pain, mental health 

comorbidities, intervention setting, and demographics? 

b. How is pain assessed in clinical trials for comorbid chronic pain and history of mTBI in 

Veterans and Servicemembers?
Chronic Pain and mTBI Evidence Synthesis Program

16

Figure 1. Analytic Framework 

Abbreviations: KQ=Key Question; mTBI=Mild traumatic brain injury; QOL=Quality of Life

SEARCH STRATEGY

Search strategies were developed in consultation with a research librarian and were peer 

reviewed by a second research librarian using the instrument for Peer Review of Search 

Strategies (PRESS).

31 We conducted a review of the literature by systematically searching, 

reviewing, and analyzing the scientific evidence as it pertains to the research questions. To 

identify relevant studies, we searched Ovid Medline; Ovid EBM Reviews: Cochrane Central 

Register of Controlled Trials, Cochrane Database of Systematic Reviews; Ovid PsycINFO; 

CINAHL; Scopus (conference abstracts only); Google Scholar; and Epistemonikos. We searched

all available years of publication from database inception (1946 for Ovid MEDLINE®) through 

February 7, 2020 (March 4, 2020 for Medline). In the Medline database, we were able to further 

limit the population with search terms to identify Veterans and/or Servicemembers, and we also 

conducted a supplementary search with Veteran/Servicemember terms in PsycINFO. We 

reviewed the bibliographies of relevant articles and contacted experts to identify additional 

studies. To identify in-progress or unpublished studies, we searched ClinicalTrials.gov, and the 

World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; See 

Appendix A for full search strategies). 

STUDY SELECTION

Criteria for population, interventions, comparators, outcomes, timing, and setting (PICOTS) 

were developed in collaboration with our operational partners and TEP (see Table 1). Two 

investigators independently reviewed the first 42% of titles and abstracts for relevance in order to 

establish consistency in application of inclusion and exclusion criteria. The remaining titles and 

abstracts did not contain relevant keywords and were assessed for inclusion by 1 reviewer. Two 

reviewers then independently assessed the full text of all citations included at the abstract 

screening phase. All discordant results were resolved through consensus or consultation with a 

third reviewer. Articles meeting eligibility criteria were included for data abstraction. 

Veterans and 

Servicemembers

Veterans and 

Servicemembers 

with a history of 

mTBI and 

chronic pain

Harms

Suiciderelated 

outcomes

Benefits: Patient, 

and utilization 

outcomes (eg, 

reduced pain, 

symptom 

improvement, 

QOL, treatment 

adherence, etc) 

KQ3

Interventions

KQ3

KQ1

KQ2
Chronic Pain and mTBI Evidence Synthesis Program

17

For Key Questions 1 and 2, we included primary studies reporting chronic pain prevalence 

estimates in US Veterans and/or SMs with a history of mTBI. For Key Question 3, we included

randomized and non-randomized controlled trials on interventions for chronic pain in Veterans 

and/or SMs with a history of mTBI from any country. Cohort, prospective, and retrospective 

studies were also includable for KQ3. Chronic pain was defined as pain lasting or recurring for 

more than 3 months.1 We considered any pain measure that was not clearly described as 

measuring acute pain to be chronic pain (eg, pain over last 30 days, headaches, etc), along with 

proxies for chronic pain such as diagnosis codes in healthcare records, analgesic medication use, 

and conditions usually accompanied by chronic pain (eg, arthritis). We included prevalence 

estimates for these definitions of chronic pain from any study population that was defined as 

having a history of mTBI, granted that a clear definition of mTBI was provided. For this report, 

mild TBI was defined using the VA and Department of Defense common definition of an 

external force to the head followed by immediate neurological symptoms as indicated by ≤30 

minutes of loss of consciousness, 0-1 days of posttraumatic amnesia, or up to 24 hours of altered 

mental status; individuals had to have normal structural imaging, if completed.2 We excluded 

studies that reported results for a mixed TBI population (mild plus moderate and/or severe) based 

on the definition of mTBI (See Table 1 and Appendix B for details). Citation lists of included 

systematic reviews were reviewed for relevant studies. For each key question of interest, we used 

a “best evidence” approach to guide additional study design criteria depending on the question 

under consideration and the literature available.32
Chronic Pain and mTBI Evidence Synthesis Program

18

Table 1. PICOTS by Key Question

Key 

Questions: 

KQ1: What is the prevalence of 

chronic pain in US Veterans or 

Servicemembers with a history 

of mTBI?

a. What are the most common 

types of chronic pain in US 

Veterans or 

Servicemembers with a 

history of mTBI?

b. Do the prevalence or types 

of chronic pain experienced 

by US Veterans or 

Servicemembers with a 

history of mTBI differ by 

mTBI etiology?

c. How do estimates of the 

prevalence of chronic pain 

and mTBI in US Veterans or 

Servicemembers differ 

according to pain 

measurement methods or 

definitions?

KQ2: What is the risk of suicide in US Veterans or 

Servicemembers with chronic pain and a history of 

mTBI?

a. How does the prevalence of suicide-related 

outcomes in US Veterans or Servicemembers 

with a history of mTBI and chronic pain compare 

to US Veterans or Servicemembers with no 

mTBI history and/or no chronic pain? 

b. How does the prevalence of suicide-related 

outcomes in US Veterans or Servicemembers 

with chronic pain and history of mTBI compare to 

civilians with chronic pain and history of mTBI?

c. How does the prevalence of suicide-related 

outcomes in US Veterans or Servicemembers 

with chronic pain and a history of mTBI vary 

depending on mTBI etiology?

d. How does the prevalence of suicide-related 

outcomes in US Veterans or Servicemembers 

with chronic pain and a history of mTBI vary 

depending on prescription opioid use or opioid 

use disorder?

KQ3: What are the benefits and harms 

of interventions to treat chronic pain in 

Veterans or Servicemembers with a 

history of mTBI?

a. Do the benefits or harms differ by 

mTBI etiology, type of chronic pain, 

mental health comorbidities, 

intervention setting, and 

demographics?

b. How is pain assessed in clinical 

trials for comorbid chronic pain and 

history of mTBI in Veterans and 

Servicemembers?

Population US Veterans or Servicemembers with mTBI and chronic pain or headaches; studies 

reporting a mixed sample of mild and moderate/severe TBI will be excluded if mTBI 

results are not reported separately

Veterans or Servicemembers from any 

country with mTBI and chronic pain or 

headaches; studies reporting a mixed 

sample of mild and moderate/severe TBI 

will be excluded if mTBI results are not 

reported separately

Intervention NA Pharmacologic, nonpharmacologic, and 

complementary and integrative health 

interventions

Comparator mTBI injury type, direct comparisons to those with no mTBI history and/or no chronic 

pain, direct comparisons of US Veterans or Servicemembers and civilians

Placebo, active comparator, usual care, 

wait-list control, pre-post

Outcome Prevalence, demographics, 

chronic pain types

Suicide-related outcomes (including suicide, suicidal 

ideation/intent/plan, and suicidal self-directed harm)

Benefits: Intermediate and patient 

outcomes, utilization (eg, reduced pain, 

mental health diagnosis/symptoms, 
Chronic Pain and mTBI Evidence Synthesis Program

19

opioid use; better QOL, functioning, 

treatment adherence)

Harms: AEs, SAEs, withdrawals due to 

AEs 

Timing Any

Setting United States Any

Study 

Design

Primary studies that include frequencies; Systematic reviews*. Exclude: Case 

studies/reports, non-systematic reviews, modeling studies. 

RCT, NRCT, cohort, prospective, 

retrospective studies; Systematic 

reviews*. Exclude: Case studies/reports, 

non-systematic reviews, modeling 

studies.

* Reference lists from relevant systematic reviews were reviewed.

Abbreviations: AE=adverse event; mTBI=mild traumatic brain injury; NA=not applicable; NRCT=non-randomized controlled trial; PICOTS=population, 

interventions, comparators, timing, setting, and study design; QOL=quality of life; RCT=randomized controlled trial; SAE=severe adverse event; US=United 

States
Chronic Pain and mTBI Evidence Synthesis Program

20

DATA ABSTRACTION

Data from studies meeting inclusion criteria were abstracted by 1 reviewer and confirmed by at 

least 1 additional reviewer. From each study, we abstracted the following a priori-defined 

categories of data when reported in the publications: study design, sample size, setting,

population characteristics (including demographics, military service characteristics, and mental 

health comorbidities where available), definitions and operationalizations of mTBI and pain, 

participant inclusion and exclusion criteria, and results. In studies where comparison data were 

presented for groups without mTBI, these pain prevalence estimates were also abstracted. For 

intervention studies, we also abstracted intervention and comparator characteristics including 

dosage, timing, and duration of treatment, duration of follow-up, adjunctive interventions (if 

applicable), and behavioral and health outcomes, as well as relevant harms.

QUALITY ASSESSMENT

Two reviewers independently assessed the methodological quality of each study using 

established methods for each study design. To assess risk of bias (RoB), we used the Cochrane 

Risk-of-Bias 2.0 criteria33 for RCTs and the Risk of Bias in Non-randomized Studies – of 

Interventions (ROBINS-I)34 for non-randomized intervention studies. We adapted the NewcastleOttawa Scale35 supplemented with another critical appraisal tool for prevalence studies36 for all 

other study designs (see Appendix C). Ratings of quality were specific to the outcome of interest 

(ie, prevalence of chronic pain or suicide for KQs 1 & 2 and treatment of chronic pain in KQ3). 

Disagreements were resolved by consensus of a third reviewer and/or the entire review team.

DATA SYNTHESIS

We qualitatively synthesized the evidence for all key questions and presented the findings in 

tables. We were not able to conduct quantitative meta-analyses for prevalence estimates because 

of the heterogeneity of study populations and chronic pain and mTBI measures across studies. 

Neither were we able to combine intervention studies due to the small number of studies and 

heterogeneity of interventions and outcomes.

RATING THE BODY OF EVIDENCE

We assessed the overall strength of evidence (SOE) for KQ3 outcomes using a method 

developed for the Agency for Healthcare Research and Quality’s (AHRQ) Evidence-based 

Practice Centers (EPCs).37 The AHRQ EPC method considers study limitations, directness, 

consistency, precision, and reporting bias to classify the strength of evidence for individual 

outcomes independently for randomized controlled trials (RCTs) and observational studies, with 

supplemental domains of dose-response association, plausible confounding that would decrease 

the observed effect and strength of association, as well as separate guidance for applicability.38

Ratings were based on the following criteria: 

• High: Very confident that the estimate of effect lies close to the true effect for this 

outcome. The body of evidence has few or no deficiencies, the findings are stable, and 

another study would not change the conclusions.
Chronic Pain and mTBI Evidence Synthesis Program

21

• Moderate: Moderately confident that the estimate of effect lies close to the true effect for 

this outcome. The body of evidence has some deficiencies and the findings are likely to 

be stable, but some doubt remains. 

• Low: Limited confidence that the estimate of effect lies close to the true effect for this 

outcome. The body of evidence has major or numerous deficiencies (or both). Additional 

evidence is needed before concluding either that the findings are stable or that the 

estimate of effect is close to the true effect.

• Insufficient: No evidence, unable to estimate an effect, or no confidence in the estimate 

of effect for this outcome. No evidence is available, or the body of evidence has 

unacceptable deficiencies, precluding reaching a conclusion.
Chronic Pain and mTBI Evidence Synthesis Program

22

RESULTS

We reviewed a total of 2,081 studies. After title and abstract review, 174 met inclusion criteria. 

Upon full-text review, we included a total of 27 prevalence studies, 2 RCTs, and 1 pre-post study

(see Figure 2).
Chronic Pain and mTBI Evidence Synthesis Program

23

Figure 2. Literature Flow Chart 

174 Potentially relevant 

articles for full text review

144 Excluded publications†: 

27 Excluded publication type

82 Excluded population

25 No outcome of interest

8 Excluded study design

2 Duplicate publication of same study

KQ 1:

27 articles (26 

studies)

21 Citations identified from reference 

lists of relevant articles and reviews, 

key experts, and other sources

2,102 Citations compiled for 

review of titles and abstracts

30 Total included studies

2,081 Citations identified from electronic database searches*: 

653 from PubMed/Ovid MEDLINE (with Veteran search term limiter) March 5, 2020

545 from PsycINFO February 7, 2020

202 from Ovid EBM Reviews (CDSR, CCRCT) February 7, 2020

136 from CINAHL February 10, 2020

121 from Scopus February 10, 2020

95 from Epistemonikos February 10, 2020

210 from ClinicalTrials.gov February 10, 2020

114 from WHO ICTRP February 10, 2020

5 from Google Scholar February 10, 2020

1,928 Titles and abstracts excluded 

for lack of relevance

KQ 3:

2 RCTs

1 pre-post study

KQ 2: 

1 study

*after deduplication. KQ = Key Question

†

See Appendix D for full list of excluded publications.

Note: KQ2 study is also included in KQ1.
Chronic Pain and mTBI Evidence Synthesis Program

24

KEY QUESTION 1: What is the prevalence of chronic pain in US 

Veterans or Servicemembers with a history of mTBI?

Summary of Findings

We found 27 articles that reported chronic pain prevalence estimates for Veterans and/or 

Servicemembers (SMs) with a history of mTBI. General chronic pain prevalence was reported in

8 studies,4,25,39-44 and head pain (eg, headaches and/or migraines) in 23 studies.6,7,15,39,40,42,44-60

Other types of chronic pain for which prevalence estimates were reported included: back pain 

(10 studies7,15,40,44,49,52,53,56,59,60); neck pain (5 studies7,40,44,52,53); arm, leg, and/or joint pain (9 

studies15,39,42,49,52,53,56,59,60); abdominal/stomach pain (5 studies15,40,56,59,60); chest pain (3

studies15,59,60); sexual pain/problems (3 studies15,59,60), prescription pain medication use (4

studies40-42,54,61 ), arthritis (2 studies40,57); and other pain (4 studies7,39,40,42). Three articles 

included data from the 4-site VA/Department of Defense (DoD) Chronic Effects of Neurotrauma 

Consortium (CENC) longitudinal study,

41,57,61 albeit with different subsets of the total sample, 

and therefore we only included data that was not duplicative from those articles – taking the 

prevalence estimate with the largest denominator when more than 1 estimate for the same 

measure was available. Sample sizes ranged from 4047 to 102,05545 Veterans or SMs with history 

of mTBI. Studies also varied widely in target population (eg, SMs or Veterans, geographic 

region, era served, comorbidities) and definitions and measures used to classify mTBI and 

chronic pain. Characteristics of the studies are in Table 2. Prevalence estimates from these 

studies are provided in Tables 3 through 5.
Chronic Pain and mTBI Evidence Synthesis Program

25

Table 2. Characteristics of studies reporting prevalence of chronic pain in Veterans/Servicemembers with a history of mTBI

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

BeswickEscanlar, 201645

N=222,036

Multi-site: 

Military Health 

System

2006-2015

Cohort – 

retrospective. 

N=102,055

EHR (based on

incident ICD

diagnosis codes)

between 2006 and 

2014, with 1-year 

follow-up period 

(2006-2015).

Active component Army, 

Navy, Air Force, and 

Marine Corps SMs with

no prior history of 

medical care for TBI, 

headache, or migraine 

documented in EHR. 

Age: 55.2%<24 yrs; 33.3% 

25-24 yrs; 9.8% 35-44 yrs;

1.6% 45-54 yrs; 0.1% 55+

yrs.

Female: 8.1%.

Race: 76.4% White; 12.1%

African-American/Black;

11.5% other.

100% SMs.

PTSD: 22.2%.

X

Brickell, 201442

N=167

1 site: WRAMC

Dates NR

Cohort – 

prospective. 

N=167

Routine 

comprehensive 

clinical evaluation by 

healthcare 

professional; 

mTBI=PTA<24 hrs

and LOC<15 mins

(could have

intracranial 

abnormality).

SMs with mTBI and 

polytrauma sustained 

during deployment

(combat or other) who 

had undergone a TBI 

clinical evaluation within 

the first 3 months of 

injury and participated in 

≥1 follow-up telephone 

interview. 

Age: 27.6 (7.0) yrs.

Female: 3.6%. 

100% SM. 

Blast: 74.3%. 

Wounded OIF: 79.6%. 

Wounded OEF: 13.2%. 

Wounded Other: 7.2%. 

X X X X X

Couch, 201646

N=110

1 Site: 

Oklahoma City 

VA outpatient 

clinic designed 

to assist 

N=55

mTBI with LOC: 

n=23

mTBI with AOC: 

n=20

Male post-deployment, 

Post-9/11 Veterans that

participated in this 

specialty clinic. All were

age 20-60, confirmed to 

have deploymentLOC:

Age: 20-29=35%; 30-

39=39%, ≥40=26.2%. 

AOC:

Age: 20-29=35%; 30-

39=40%; ≥40=25%. 

Female: 0%.

X
Chronic Pain and mTBI Evidence Synthesis Program

26

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Veterans in 

return to civilian 

life. 

7/2012 - 8/2014.

Case-control.

VA/DoD common 

definition, based on 

TBI screen followed 

by TBI clinic 

evaluation.

related TBI (cases), and 

4-11 years post-TBI.

Race NR.

100% Veterans. 

FarrellCarnahan, 

201547

N=112

4 sites: VA 

Polytrauma 

Rehabilitation 

Centers (PRC). 

Jan 2009–Mar

2013. 

Cross-sectional. 

N=40

VA/DoD common 

definition, based on 

VA PRC TBI Model 

System Form 1 

inpatient data 

collection at time of 

study enrollment. 

Veterans 18+ yrs 

receiving care for TBI 

and/or TBI-related 

issues in VA inpatient 

rehabilitation program

and enrolled in VA PRC 

TBI Model System

within 1-year of injury. 

Also required TBI 

severity information and 

at least partial 

completion of a 1-year 

follow-up assessment 

(including NSI and/or 

patient proxy).

Age: 29 (13) yrs.

Female: 7%. 

Race: 70% White. 

100% Veteran. 

Cause of injury: motorvehicle related 10/40 

(25%); other violence 

(blast) 21/40 (53%); all 

other 9/40 (23%). 

Injured during deployment: 

26/40 (65%). 

X

Hoge, 200815

N=2,525

Single-site: 

Walter Reed 

Army Institute of

Research. 

2006. 

Cross-sectional. 

N=384

(LOC=124; 

AOC=260)

Screening 

questionnaire

consistent with 

VA/DoD common 

definition.

SMs (active or reserve 

US Army combat 

infantry brigade) 3-4 

months after return from 

combat deployment to 

Iraq. Exclusions:

missing data from injury

questions or reported 

having had a head 

LOC vs AOC:

Female: 1/123 (0.8%) vs 

3/258 (1.2%). 

Age<30 yrs: 79/123 

(64.2%) vs 149/257 

(58.0%). 

100% SMs. 

PTSD: 54 (43.9%) vs 71 

(27.3%).

X X X X X X
Chronic Pain and mTBI Evidence Synthesis Program

27

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

injury without LOC or 

AOC.

Major depression: 27 

(22.9%) vs 21 (6.6%). 

Mechanism of injury: 

Blast or explosion 98 

(79.0%) vs 189 (72.7%); 

Bullet 6 (4.8%) vs 2 (0.8%); 

Fragment or shrapnel 31 

(25.0%) vs 48 (18.5%); Fall 

38 (30.6%) vs 73 (28.1%); 

Vehicle accident 38 

(30.6%) vs 47 (18.1%); 

Other 16 (12.9%) vs 23 

(8.8%).

Hoot, 201841

N=454

4 sites: VAMCs 

in Richmond, 

VA; Tampa, FL; 

San

Antonio, TX; and 

Houston, TX.

2016-2017. 

CENC. 

Cross-sectional.

N=379

DoD/VA common 

definition. Each 

potential concussive 

event identified was 

investigated via the 

VCU rCDI. 

Post-9/11 Veterans/SMs 

with combat exposure.

Exclusion: (1) history of 

moderate or severe TBI; 

(2) history of major

neurologic or psychiatric

disorder.

Median age: 36.0 (range 

22-64).

Female: 11.6%.

Race: 67.3% White; 22.7%

African-American/Black;

10.0% other.

Ethnicity: 23.6%

Hispanic/Latino.

PTSD (MINI): 31.2%.

Depression (PHQ-9):

43.1%.

X X

Jackson, 201648

N=1,312

Numerous: 

Nationally 

dispersed 

Veterans 

N=612

VA/DoD common 

definition, based on 

VA 4-item TBI 

screen plus clinical 

Post-9/11 reserve or 

active duty (Army and 

Marine) Veterans with 

history of mTBI (with or 

without LOC) 

Age: 37.1 (9.8) yrs.

Female: 52.8% female. 

Race/Ethnicity: 66.5% 

White; 15.6% African 

American/Black; 13% other.

100% Veterans.

X
Chronic Pain and mTBI Evidence Synthesis Program

28

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

enrolled in 

Project VALOR

2009-2012

Cohort – 

retrospective. 

interview by 

doctoral-level 

clinician.

required to have 

undergone a mental 

health evaluation at a 

VA facility, indicated by 

a diagnostic interview or 

psychotherapy 

procedure code July 

2008-Dec 2009. Must 

not have been 

participating in a clinical 

trial at the time of 

enrollment or have 

moderate/severe TBI, or 

TBI of unknown 

severity. Individuals with 

probable PTSD were 

oversampled at a 3:1 

ratio; females were 

oversampled at a 1:1 

ratio.

Major depression: 38.5%.

Current PTSD: 51.9%. 

PTSD + Depression: 

30.9%. 

King, 201440

N=842

Multi-site: VA 

Integrated

Service Network 

2 (upstate NY + 

parts of northern

PA).

Oct 2001-Sept 

2011. 

Cross-sectional.

N=421

≥1 encounter with 

ICD code 310.2

(post-concussion 

syndrome).

Post-9/11 Veterans who 

used VA primary care. 

Age: 30.3 (7.6) yrs.

Female: 4%. 

100% Veterans.

X X X X X X X X
Chronic Pain and mTBI Evidence Synthesis Program

29

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Kulas, 201839

N=164,884

Muti-site: 

National data

(VA EHR)

10/1/2011 - 

9/30/2012. 

Cohort – 

retrospective.

N=32,316 

(23,063 

mTBI+PTSD; 9,253 

mTBI no PTSD)

EHR (based on ICD

diagnosis codes)

during fiscal year 

2012.

All Post-9/11 Veterans 

who received care in 

VHA and had ≥1 ICD

diagnosis code for

mTBI.

mTBI + PTSD group:

Age: 32.8 (8.3) yrs.

Female: 5%. 

mTBI no PTSD group: 

Age: 32.1 (8.6) yrs.

Female: 8%. 

X X X X

Lew, 200925

N=340

Single-site: VA 

level 2 

polytrauma 

clinic.

Jan 1, 2007 - 

Oct 27, 2008 (22 

months). 

Cross-sectional.

N=227

Clinical 

determination of 

mTBI on CTBIE

based on VA/DoD 

common definition.

All Post-9/11 Veterans 

with persistent postconcussive symptoms

seen at the polytrauma 

clinic.

NR X

MacGregor, 

201349

N=992

Multi-site: 

Navy/Marine 

deployment 

health database.

Mar 2004 – Apr

2008. 

Cohort – 

retrospective.

N=334

EHR: ICD diagnosis

codes indicative of 

TBI with 

corresponding 

Abbreviated Injury 

Score values of 1 or 

2. 

Iraq War SMs

(Navy/Marines) who 

sustained minor to 

moderate injuries and

completed a PDHRA 

after deployment (within 

1 year of injury).

Age: 23.3 yrs (range 18-

45). 

Female: 0.3%.

Race: NR.

Mechanism of injury:

Battle, blast: 297 (88.9%). 

Battle, nonblast: 8 (2.4%). 

Nonbattle: 29 (8.7%). 

X X X
Chronic Pain and mTBI Evidence Synthesis Program

30

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Patil, 201150

N=246

Single-site: 

large, 

midwestern

polytrauma 

network site.

June 15, 2007 - 

July 15, 2009. 

Cohort – 

retrospective.

N=246

(56 evaluated in 

Neurology)

VA/DoD common 

definition, based on 

VA CTBIE.

Post-9/11 combat 

Veterans receiving care 

at a VA polytrauma

network site with 

combat-related mTBI. 

Age: 27.9 (6.3) yrs.

Female: 7.7%.

Race: 85.8% White. 

Ethnicity: 19.1% Hispanic. 

Mechanism of injury:

1+ blast exposure: 65%.

X

Powell, 201543

N=171

Single-site: 

Boston VA

TRACTS Center 

of Excellence.

Cross-sectional. 

N=171

Clinical interview

by doctoral-level

psychologist

(reviewed by 3+ 

doctoral-level 

psychologists for 

consensus 

diagnosis). 

Post-9/11 Veterans. 

Excluded: (a) a history 

of seizures; (b) prior 

serious medical illness; 

(c) current active

suicidal and/or

homicidal ideation,

intent, or plan requiring

crisis intervention; (d)

DSMIV-TR diagnosis of

current bipolar disorder,

schizophrenia, or

other psychotic disorder

(except psychosis not

otherwise specified

[NOS] due to traumarelated hallucinations);

or (e) cognitive disorder

due to general medical

condition other than

Age: 33.3 (8.6) yrs.

Female: 13.5%. 

Race/Ethnicity: 

Black/African-American

10.5%; Hispanic/Latino

17%; White 68.4%. 

Current mood disorder: 

30.4%. 

Current anxiety disorder: 

22.2%. 

X
Chronic Pain and mTBI Evidence Synthesis Program

31

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

TBI. Participants with 

any history of moderate 

to severe TBI were 

excluded.

Pugh, 20197

N=527,381

Multi-site: VA

EHR data.

Oct 1, 2001 -

September 30, 

2011. 

Cross-sectional. 

N=93,003

VA/DoD common 

definition, based on 

comprehensive 

algorithm using DoD

trauma data, VA 

CTBIE data, and 

ICD diagnosis 

codes.

Veterans who met 

criteria for mTBI. 

Included: (a) entered VA 

care Oct 1, 2001-

September 30, 2011; (b) 

received ≥5 years of VA 

care (inpatient, 

outpatient, or pharmacy) 

before Sept 30, 2014; 

and (c) received ≥1 year 

of care after 2007. 

Age: 29.8 (7.8) yrs.

Female: 6.0%.

Race/Ethnicity: White 

69.6%; 

Black/African American

13.3 %; Hispanic 12.6%; 

Asian 2.1%; Native 

American/Pacific Islander

1.7%. 

100% Veteran. 

X X X X

Romesser, 

201244

N=433

2 sites: VAMC

polytrauma 

clinics.

Cohort – 

retrospective. 

N=354

Clinical interview:

Self-reported history 

of mTBI based on 

VA/DoD common 

definition and 

identifying a 

mechanism of injury. 

Post-9/11 Veterans with 

mTBI referred to VA

polytrauma clinic. 

Excluded: Incomplete 

demographic and/or

injury severity 

characteristics, missing 

pain or headache data, 

or with ≥2 items missing

on PTSD Checklist.

Age: 31.0 (8.2) yrs.

Female: 4.6%. 

Race/Ethnicity: 

Black/African-American

15%; White 63.7%; 

Hispanic 17.3%; other 

3.9%. 

X X X X

Ruff, 20086

N=126

Single-site: 

Cleveland, OH 

N=126

VA/DoD common 

definition, based on 

VA CTBIE.

Post-9/11 combat 

Veterans receiving care 

at a VA polytrauma

network site with 

Demographics NR.

100% Veteran. 

X
Chronic Pain and mTBI Evidence Synthesis Program

32

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

VA polytrauma 

network site.

Dates NR. 

Cross-sectional.

deployment- and blastrelated mTBI. 

Schwab, 201751

N=1,567

2 sites: Fort 

Carson,

CO, and Fort 

Bragg, NC.

Cohort – 

prospective. 

N=557 at baseline; 

358 with mTBI 

completed 3-month 

follow-up.

VA/DoD common 

definition, based on 

screening followed 

by OSU TBI-ID

interview.

Post-9/11 Army SMs

recently returned from 

Iraq/Afghanistan with 

positive TBI screen.

Excluded: having been 

medically evacuated

from theater, 

determined that likely 

incurred more than a 

mild TBI, and likely 

symptom exageration. 

Age: 27 (6) yrs.

Female: 8%. 

Race/ethnicity: 65.8% 

White; 13.6% Hispanic; 

11.2% African 

American/Black; 9.4%

multiple. 

Experienced blast: 67%. 

PTSD screen: 15% 

positive. 

X

Seal, 20174

N=116,913

Multi-site: VA 

CTBIE

database. 

October 2007-

March 2015. 

Cohort – 

retrospective. 

N=65,675

Clinical 

determination of 

mTBI on CTBIE

based on VA/DoD 

common definition.

Post-9/11 Veterans with 

determinate TBI finding 

on CTBIE, VA EHR data 

during year before or 

after CTBIE, sufficient 

CTBIE data to classify 

TBI severity, complete 

data. 

Age: mean NR.

Female: 6.1%. 

Race: 39.9% Other-thanwhite. 

100% Veteran. 

PTSD: 65.8%. 

Depression: 39.4%. 

Alcohol Use Disorder: 

15.9%. 

Drug Use Disorder: 8.7%.

X

Suri, 201952

N=36,880

Multi-site: VA 

CTBIE database

N=23,703

VA/DoD common 

definition, based on 

CTBIE.

Post-9/11 Veterans 

aged 18-65 years who 

had:

(1) complete data for

the presence and/or

Age: 33.3 (7.7) yrs.

Female: 5.1%. 

Race: Asian 2.0%; 

Black/African-American 

X X X X
Chronic Pain and mTBI Evidence Synthesis Program

33

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

7/1/2009 -

9/30/2013. 

Cohort – 

prospective. 

duration of the most 

severe episodes of 

deployment-related 

LOC, PTA, and/or AOC

experienced; (2) 

complete data for the 

CTBIE clinician's overall 

assessment of 

deployment-related TBI 

history (Y/N); (3) 

agreement between #1 

and #2; and (4) no selfreported occurrences of 

pre-deployment or postdeployment TBI.

13.2%; Hawaiian/Pacific 

Islander 1.5%; 

American Indian/Alaska 

Native 1.3%; 

White/caucasian 69.7%; 

Unknown/NR 12.4%. 

Depression: 37.0%. 

PTSD: 67.7%. 

Alcohol abuse/dependence:

7.2%. 

Drug abuse/dependence: 

2.4%. 

Non-blast TBI only: 21.8%. 

Blast TBI only: 46.6%. 

Blast+non-blast TBI: 31.6%.

Suri, 201753

N=2,187

24 VA facilities 

nationwide: 

CTBIE

database.

7/1/2009- 

9/30/2013. 

Cohort – 

prospective

survey ~3 yrs 

after CTBIE). 

N=1,683 

VA/DoD common 

definition, based on 

CTBIE. 

18-65 years; Agreement

between clinician TBI

impression and

expected diagnosis

based on VA/DoD

criteria for AOC, LOC,

and PTA; Past TBI

history limited to

nondeployment-related

TBIs only.

Age: 36.6 (9.2) yrs.

Female: 8.7%.

Race: NR. 

100% Veteran. 

Depression: 29.8%.

PTSD: 48.6%.

Alcohol abuse: 4.8%.

Drug abuse: 1.6%.

Non-blast TBI only: 25.8%.

Blast TBI only: 56.4%.

Both blast/non-blast TBI: 

17.8%. 

X X X X
Chronic Pain and mTBI Evidence Synthesis Program

34

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Theeler, 201254

N=978

Single-site: 

Madigan Army 

Medical Center. 

Cross-sectional. 

N=978

Screening: Initial 2-

question screen 

followed by 10-

question screen

(scored in a 

standardized 

manner from 0 to 

39);

concussion=score of 

≥5 on the 2-plus-10 

questionnaire. SMs 

with positive screen 

then evaluated in 

TBI clinic.

SMs who had a 

deployment-related 

concussion in Iraq or 

Afghanistan. 

NR. X X

Tsao, 201755

N=2,612

3 sites: Camp 

Lejeune, NC; 

Twentynine 

Palms, CA; and 

Kaneohe Bay, 

HI. 

4/2010 - 6/2013. 

Cross-sectional.

N=2,612

VA/DoD common 

definition, based on 

screening questions. 

Male SMs (Marines) 

were 2-8 weeks postdeployment in Iraq 

and/or Afghanistan and 

saw greatest amount of 

combat but did not 

sustain injury requiring 

medical evacuation and 

were not on restricted 

duty.

Median age: 22 years 

(range 19-50)

95% were<33 years

99% were<39 years 

Female: 0%

100% SMs

X

Vanderploeg, 

200956

N=4,462

N=278 Male, Vietnam-era,

Army Veterans who 

had: (1) first entered the 

military between Jan 

Age: 78%<40 yrs.

Race: 16% Other-thanwhite.

X X X X
Chronic Pain and mTBI Evidence Synthesis Program

35

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Randomlysampled US 

Veterans flown 

to VAMC and 

University of 

South Florida, 

Tampa, FL. 

Mid-1980s. 

Cross-sectional. 

Those who had a 

head injury with

AOC. 

Interview: (1) Since 

your discharge from

active duty, have 

you injured your 

head? and (2) Did 

you lose

consciousness as a 

result of the head 

injury? (If 

participants

were unclear if they 

had lost 

consciousness, they 

were asked if

they had “blacked 

out” in the accident.).

1965-Dec 1971; (2) 

been on active duty for 

≥4 months; (3) served

only 1 tour of duty; (4) 

obtained a military 

occupational specialty; 

and (5) achieved a pay 

grade ≤E-5 (sergeant)

on discharge. 

Exluded: Participants 

that required 

hospitalization after their 

head injury. 

100% Veteran; 

Approximately half the 

sample had served in 

Vietnam, whereas the other 

half had served elsewhere 

(ie, United States, Korea, 

Germany).

Walker, 2018a57

N=492

4 sites: VAMCs 

in Richmond, 

VA; Tampa, FL; 

San

Antonio, TX; and 

Houston, TX.

Consented for 

study (CENC) 

prior to Sept. 

2017.

N=414

VA/DoD common 

definition. Each 

potential concussive 

event identified was 

investigated via the 

VCU rCDI. 

Post-9/11 Veterans/SMs 

with combat exposure.

Exclusion: (1) history of 

moderate or severe TBI; 

(2) history of major

neurologic or psychiatric

disorder.

Age: 36.0 yrs (31.0, 47.0).

Female: 11.8%. 

Race: 66.2% White; 23.4% 

African-American/Black; 

10.4% other. 

Ethnicity: 23.4% Hispanic 

or Latino. 

X X
Chronic Pain and mTBI Evidence Synthesis Program

36

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

Cross-sectional.

Webb, 201558

N=513,893

Multi-site: 

Military Health 

System.

2001-2008.

Cohort – 

retrospective. 

N=5,065

EHR (based on ICD

diagnosis codes).

Air Force SMs who 

served on active duty 

for ≥180 days between 

Oct 1, 2001 -Sept 30,

2008 with incident 

cases of mTBI.

Excluded: history of 

mTBI or other head 

injuries in the 2 years 

prior to entering the 

study. 

Born before 1965: 6.7%.

1966-1975: 15.7%. 

1976 and later: 77.6%. 

Female: 18%. 

Race/ethnicity: 75.1%

White; 11.6% AfricanAmerican/Black; 2.5%

Asian/Pacific Islander; 6.5%

Hispanic; 0.7% Native 

American; 3.7%

Other/Unknown.

100% SMs.

X

Wilk, 201259

N=1,502

Single-site: 

Walter Reed 

Army Institute of

Research. 

Nov-Dec 2008. 

Cross-sectional. 

N=260

(LOC=86; 

AOC=174)

Screening 

questionnaire

consistent with 

VA/DoD common 

definition.

SMs (3 Army brigade 

combat teams from 1 

Active Component 

infantry division) 4-6 

months after return from 

combat deployment to

Iraq or Afghanistan who 

met criteria for mTBI.

72%<30 yrs.

Female: 9%. 

LOC vs AOC: 

PTSD (PCL-17): 52% vs 

29% . 

Depression (PHQ-9): 23% 

vs 16%. 

X X X X X X

Wilk, 201060

N=3,952

Single-site: 

Walter Reed 

Army Institute of

Research. 

2006-2007. 

Cross-sectional.

N=587

(LOC=201; 

AOC=373)

Screening 

questionnaire

consistent with 

SMs (1 Army National 

Guard and 2 Active 

Duty infantry brigades)

3-6 months after return

from combat

deployment in Iraq

who met criteria for

mTBI.

66.9%<30 yrs.

Female: 1.7%.

LOC blast vs non-blast: 

AOC blast vs non-blast:

PTSD: 

44.7% vs 38.5%.

30.0% vs 29.1%.

Major depression: 

X X X X X X
Chronic Pain and mTBI Evidence Synthesis Program

37

Author, Year

N total pts*

Setting

Dates

Study Design

Data Collection

mTBI

N pts with history of 

mTBI

mTBI assessment 

and definition

Eligibility 

study 

inclusion/exclusion 

criteria

Demographics

Age: mean (SD)

Female: %

Race: %

SMs or Veterans

Mental health 

comorbidities, mTBI injury 

details (mechanism, # of 

mTBIs)

Type(s) of CP assessed

GeneralHeadBackNeckArm/leg/jointStomach/ abdominalChestSexualPain medication useArthritisOther

VA/DoD common 

definition.

21.2% vs 15.8%.

10.2% vs 16.0%.

Alcohol misuse: 

39.0% vs 42.1%.

28.2% vs 37.4%.

Total Studies: 8 23 10 5 9 5 3 3 4 2 3

*may include those without TBI history and/or with moderate/severe TBI

Abbreviations: AOC=Alteration of consciousness; CA=California; CENC=Chronic Effects of Neurotrauma Consortium; CO=Colorado; DoD=Department of

Defense; DVBIC=Defense and Veterans Brain Injury Center; FL=Florida; HI=Hawaii; LOC=Loss of consciousness; MINI=Mini-International Neuropsychiatric

Interview; mTBI=Mild Traumatic Brain Injury; NC=North Carolina; NR=Not reported; OH=Ohio; OSU TBI-ID=Ohio State University Traumatic Brain Injury

Identification Method; P=P-value; PDHA=Post-Deployment Health Assessment; PDHRA=Post-Deployment Health Re-Assessment; PHQ-9=9-item Patient

Health Questionnaire scale; PNS=Polytrauma Network Site; PTS=Posttraumatic Stress; PTSD=Posttraumatic Stress Disorder; SD=Standard Deviation;

SM=Servicemember; TBI=Traumatic Brain Injury; TRACTS=Translational Research Center for TBI and Stress Related Disorders; TX=Texas; US=United

States; VA=Virginia; or Veterans Affairs; VALOR=Veterans' After-discharge Longitudinal Registry; VAMC=Veterans Affairs Medical Center; VCUrCDI=Virginia Commonwealth University retrospective Concussion Diagnostic Interview; WRAMC=Walter Reed Army Medical Center
Chronic Pain and mTBI Evidence Synthesis Program

38

Detailed Results

General Chronic Pain

There were 8 studies that reported prevalence of general (or any) chronic pain among Veterans 

with mTBI: 3 were retrospective cohort studies based on VA administrative data (ie, EHR data) 

for Veterans who used VA healthcare,

4,39,40 1 was a study of injured SMs evaluated at different 

time points for approximately 5 years post-injury,42 and 4 were VA-based studies that either 

enrolled Veterans for testing or utilized chart review of patients who had been seen in TBI 

clinics.25,41,43,44 All 8 studies focused on Post-9/11 Veterans. 

A relatively robust estimate of the prevalence of general chronic pain among Veterans was 

identified by Seal et al4 in a study of 65,675 Veterans with a confirmed history of mTBI based on 

the VA’s CTBIE. In this study, the prevalence of chronic pain diagnoses (defined as those with 2 

or more International Classification of Diseases [ICD] diagnosis codes for pain, greater than 90 

days apart, in the year before or after their CTBIE) was 59%. This compared to 53% among 

those whose CTBIE did not confirm mTBI history. The strengths of this study are that it is 

broadly representative of the large population of Veteran VA users who have been diagnosed 

with mTBI by a specialist clinician using the CTBIE. Additionally, the criteria used to identify 

pain using ICD codes were relatively stringent compared to other studies that use administrative 

data. However, Veterans who complete the CTBIE are generally seeking treatment for a variety 

of post-deployment health symptoms that may or may not be related to mTBI, or pain, and thus 

symptoms may be overreported. Additionally, the use of ICD diagnosis codes in EHR data to 

estimate the prevalence of health disorders such as chronic pain may lead to over- (or even 

under-) estimation due to a variety of reasons.

3,5 Therefore, pain data from this study and other 

studies relying on CTBIE or EHR diagnosis data may not represent the true prevalence of 

chronic pain in the population of Veterans and SMs with mTBI. 

The Seal et al study4 also captured rates of pain disability, which was examined with a 5-item 

Likert scale from none to very severe interference in daily functioning and quality of life. 

Moderate-to-very severe interference qualified as pain disability, and the prevalence of pain 

interference (defined as moderate-to-severe interference in daily functioning) was 75%.4 This 

pain interference finding was consistent with a smaller study (n=354) of Veterans treated 

consecutively at 2 VA polytrauma program sites, in which 70% had reported moderate-toextreme pain interference (defined as functional limitations secondary to pain).44

The remaining studies were based on a variety of Veteran samples, measures of mTBI history, 

and definitions/measures of pain. A study by Kulas and Rosenheck39 was similar to the Seal et al

study in its use of VA EHR data for a large number of Veterans; however, rather than the 

CTBIE, this study used ICD diagnosis codes to identify Veterans with mTBI. It also examined 

comorbid PTSD. In this study, 82% of Veterans with both mTBI and PTSD diagnoses also 

carried a pain diagnosis, while 71% of those with mTBI but no PTSD had been diagnosed with 

pain (compared to 62% of those with PTSD only). This was consistent with a study by King et al

in which 2 or more ICD diagnosis codes for pain, assigned ≥90 days apart, were identified in 

76% of Veterans with mTBI (versus 52% of those without mTBI).

40 Similar figures were 

presented in a polytrauma clinic chart review study by Lew et al,

25 in which 86% of Veterans 

diagnosed with both mTBI and PTSD had been diagnosed with chronic pain, while 71% of those 

with mTBI but no PTSD had been diagnosed with chronic pain, and in a longitudinal survey of 
Chronic Pain and mTBI Evidence Synthesis Program

39

SMs with mTBI by Brickell et al, in which 67% to 89% of respondents in each wave reported 

bodily pain.42 Powell et al43 used cross-sectional data from clinical interviews of 171 Veterans 

enrolled in the VA Translational Research Center for TBI and Stress Disorders (TRACTS) 

longitudinal study at 1 VA site. Among Veterans with mTBI as confirmed via clinical interview, 

38% met study criteria for chronic pain. Hoot et al41 reported the prevalence of chronic pain 

among 379 Veterans enrolled in the CENC study with confirmed history of mTBI; 59% of 

Veterans reported moderate, severe, or extreme pain or discomfort based on a validated measure 

of pain intensity, compared to 65% of Veterans with no TBI history. (Brickell et al also reported 

pain severity among respondents in a longitudinal study of SMs and identified moderate or 

greater pain intensity among 37% to 59% of respondents across survey time points.42) 

Additional detail of these and other studies presenting general chronic pain data can be found in 

Table 3. 

Table 3. Prevalence estimates of general chronic pain from studies of 

Veterans/Servicemembers with a history of mTBI

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool 

Prevalence Results 

n (%)

Seal, 20174

n=65,675

Post-9/11 

Veterans.

EHR data Presence: Having ≥2 of the same pain 

ICD diagnosis code more than 90 days 

apart, 1 year before or after CTBIE.

38,591/65,675 (58.8%)

CTBIE Pain interference presence: Ascertained 

during the CTBIE and defined as an 

individual’s appraisal of the degree to 

which pain interferes with their daily 

functioning and quality of life. Veterans are 

prompted to endorse level on a 5-item 

scale, and responses were dichotomized 

as moderate-to-extreme versus none-tomild.

75%

Kulas, 201839

n=32,316

Post-9/11

Veterans.

EHR data Presence: Y/N of ICD diagnosis code for 

pain in EHR.

mTBI+PTSD: 81.5%

mTBI no PTSD: 70.8%

King, 201440

n=421

Post-9/11

Veterans. 

EHR data Presence: If treated for conditions 

commonly associated with pain for ≥3 

months based on ICD diagnosis codes (ie, 

if the time elapsed between encounters

with similarly coded conditions was ≥90 

days from the initial encounter).

320/421 (76.0%)

Hoot, 201841

n=379

Post-9/11 

Veterans/SMs. 

CENC sample.

EQ-5D-5L Intensity: Level of pain or discomfort.

[Note that we considered “No or slight pain 

or discomfort” = no chronic pain, while 

“Moderate, Severe, or Extreme pain or 

discomfort” = chronic pain.]

Moderate: 166/378 (43.9%)

Severe: 54/378 (14.3%)

Extreme: 4/378 (1.1%)

Moderate-to-extreme:

224/378 (59.3%)
Chronic Pain and mTBI Evidence Synthesis Program

40

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool 

Prevalence Results 

n (%)

Romesser, 

201244

n=354

Post-9/11

Veterans

assessed at 2 

polytrauma 

clinics.

Self-report Interference: Asked how much pain 

interfered with life in the past 30 days 

(moderately, severely, or extremely versus 

not at all or mild).

mTBI with no LOC (n=210) 

vs mTBI with LOC (n=144): 

Moderately: 72 (34.3%) vs 

58 (40.3%) [Total 

mTBI=36.7%]

Severely: 52 (24.8%) vs 40 

(27.8%) [Total 

mTBI=26.0%]

Extremely: 15 (7.1%) vs 12 

(8.3%) [Total mTBI=7.6%]

Severely to extremely: 67 

(31.9%) vs 52 (36.1%)

[Total mTBI=33.6%]

Moderately to extremely: 

139 (66.2%) vs 110 

(76.4%) [Total 

mTBI=70.3%]

Lew, 200925

n=227

Post-9/11 

Veterans seen 

at polytrauma 

clinic.

EHR data Presence: Chronic pain was defined as 

persisting reports of pain in ≥1 body part 

for ≥3 months after onset. 

Total mTBI: 81.9%

mTBI with PTSD: 86.2%

mTBI no PTSD: 70.5%

 

Powell, 201543

n=171 

Post-9/11 

Veterans 

enrolled in

VA TRACTS.

EHR/selfreportPresence: Veterans were determined to 

have chronic pain if pain diagnosis was 

listed as an active problem in VA EHR and 

dated prior to TRACTS testing day (n=45); 

if they were referred to a chronic pain

specialist after determined to have chronic 

pain via clinical interview (n=17); or if they 

had discussed pain that had lasted ≥3 

months during their interview (n=3).

65/171 (38.0%)

Brickell, 201442

n=167

Post-9/11 SMs.

Self-report 

telephone 

interview 

with openended 

questions

Bodily pain (other than headache) 

presence: Any pain in past month.

The telephone follow-up interview is an 

unpublished, 10-15 min, semi-structured 

interview developed specifically for this 

study.

6 mos: 78.3%

12 mos: 76.4%

24 mos: 88.9%

36 mos: 78.6%

48 mos: 66.7%

60 mos: 80.0%

Bodily pain (other than headache) 

frequency: Daily/almost daily in past 

month.

6 mos: 34.8%

12 mos: 41.6%

24 mos: 37.0%

36 mos: NR 

48 mos: 50.0%

60 mos: Unclear

Bodily pain (other than headache) 

intensity: Moderate or greater in past 

month.

6 mos: 37.0%

12 mos: 39.3%

24 mos: 59.3%

36 mos: NR

48 mos: 36.7%

60 mos: NR
Chronic Pain and mTBI Evidence Synthesis Program

41

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; EQ-5D-5L=EuroQol 

Group 5-dimension 5-level version; ICD=International Classification of Diseases; LOC=Loss of consciousness; 

mTBI=Mild Traumatic Brain Injury; NR=Not reported; OEF=Operation Enduring Freedom; OIF=Operation Iraqi 

Freedom; PTSD=Posttraumatic Stress Disorder; SM=Servicemember; TRACTS=Translational Research Center for 

TBI and Stress Related Disorders; VA=Veterans Affairs

Head Pain

We identified 23 studies reporting prevalence of head pain in Veterans with a history of 

mTBI.

6,7,15,39,40,42,44-60 Headaches and/or migraines were assessed across a range of study 

populations using a variety of pain assessment tools, including EHR data, the Neurobehavioral 

Symptom Inventory (NSI), the 15-item Patient Health Questionnaire (PHQ-15), the 6-item 

Headache Impact Test (HIT-6), and the Post-deployment Health Assessment and Re-assessment

(PDHA/PDHRA), with prevalence estimates ranging from 3%58 to 98%.

54 Two studies, 1 larger

multi-site study in Air Force SMs (n=5,065)58 and 1 very small study in OEF/OIF Veterans from 

a single site (n=43),46 specifically reported the prevalence of migraines independent of headache. 

The presence of migraines or headaches was combined in 1 large study using administrative data 

(n=102,055).45 All other studies reported prevalence of headaches, although only 9 addressed the 

severity and/or frequency of headaches.15,42,46,47,51,53,54,57

Five studies may best inform prevalence estimates of headache and/or migraine in Veterans with 

mTBI.

7,39,45,52,53 These studies were conducted in broad population samples and are most 

generalizable to the population of SMs/Veterans with mTBI; however, the range of pain 

prevalence values was broad, from 15% of a SM sample receiving head pain diagnosis codes in a 

1-year time period (compared to 3% among those without mTBI diagnosis),

45 to 94% of 

Veterans with confirmed mTBI indicating they experience headaches when asked by a clinician 

completing the CTBIE (compared to 86% of those without confirmed mTBI).

53 A large 

(n=102,055) retrospective cohort study of surveillance data from the Defense Medical 

Surveillance System (DMSS)

45 estimated a 15% prevalence of headaches or migraines in SMs 

with a history of mTBI. This was the lowest prevalence estimate among all included studies, 

with the exception of a smaller study (n=5,065) that reported a prevalence estimate of 3% among 

SMs in the 31-179-day period post-mTBI.

58 A similarly large, multi-site, cross-sectional study of 

93,003 Veterans estimated a 20% prevalence of headaches among Veterans with mTBI history, 

compared to 6% of those without.

7 The prevalence estimate was higher in a multi-site 

retrospective cohort study of 32,316 Post-9/11 Veterans: 36% of those with mTBI history had a 

headache diagnosis.

39 Among Veterans with comorbid mTBI and PTSD diagnosis, the 

prevalence of headache increased to 48% (compared to 16% among those with PTSD and no 

mTBI).

39 In another large study (n=23,703) of Post-9/11 Veterans who were confirmed with 

mTBI via a completed CTBIE, 70% reported headache pain in the past 30 days, compared to 

55% of those without confirmed mTBI.

52 A smaller study (n=1,683) across 24 VA facilities 

nationwide also utilized CTBIE data to estimate headache prevalence by intensity and found that 

approximately 94% of participants experienced any headaches and 82% of participants reported 

experiencing moderate to very severe headaches (compared to 86% and 61%, respectively,

among those without confirmed mTBI).

53

See Table 4 for additional details of headache/migraine pain measurement and prevalence 

outcomes for all included studies.
Chronic Pain and mTBI Evidence Synthesis Program

42

Table 4. Prevalence estimates of head pain from studies of Veterans/Servicemembers with 

a history of mTBI 

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details 

of assessment tool 

Prevalence Results 

n (%) 

BeswickEscanlar, 

201645

n=102,055

SMs. 

EHR data Headache or migraine presence

(incident diagnosis; yes.no): 

Presence/absence of ICD diagnosis 

code for headache or migraine in EHR

during the post-TBI 1-year follow-up 

period. 

15,519/102,055 (15.2%)

Pugh, 20197

n=93,003 

Post-9/11

Veterans.

EHR data Headache presence (yes/no): ICD 

diagnosis code in health record during 

first year of VA care. 

18,929/93,003 (20.4%)

Kulas, 201839

n=32,316

Post-9/11 

Veterans.

EHR data Headache presence (yes/no): 

Presence/absence of ICD diagnosis 

code in EHR.

mTBI+PTSD: 47.7%

mTBI no PTSD: 36.0% 

Suri, 201952

n=23,703 

Post-9/11 

Veterans.

CTBIE Headache presence (yes/no): CTBIE

questionnaire item inquires about 

headache pain in the last 30 days. 

16,534/23,703 (69.8%)

Webb, 201558

n=5,065

Post-9/11 SMs.

EHR data Headache presence (yes/no): ICD 

diagnosis code in health record after 

mTBI diagnosis. 

31-179 days post-mTBI: 

142/5,065 (2.8%) 

≥180 post-mTBI: 371/5,065 

(7.3%)

Migraine presence (yes/no): ICD 

diagnosis code in health record after 

mTBI diagnosis. 

31-179 days post-mTBI: 

79/5,065 (1.6%) 

≥180 days post-mTBI: 

211/5,065 (4.2%)

Suri, 201753

n=1,683

Post-9/11

Veterans. 

CTBIE 

(headache 

item from 

NSI)

Headache presence (yes/no) and 

severity: Presence and severity were

evaluated at the baseline CTBIE 

assessment using the NSI 5-level 

headache item ranging from 0 (“none”) 

to 4 (“very severe”) interference in past 

30 days.

Any headache: 94.1%

Severity: 

Mild: 12.5%

Moderate: 26.8%

Severe: 33.7%

Very severe: 21.1%

Total Mod-Severe: 81.6%

Tsao, 201755

n=1,022

Post-9/11 SMs.

Self-report Headache presence (yes/no): Survey 

asked if respondents experienced 

headaches (yes/no). 

1 mTBI: 499/892 (55.9%)

≥2 mTBI: 96/130 (73.8%) 

Total any # of mTBI: 

595/1,022 (58.2%)
Chronic Pain and mTBI Evidence Synthesis Program

43

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details 

of assessment tool 

Prevalence Results 

n (%) 

Theeler, 201254

n=978

Post-9/11 SMs.

Self-report Headache presence (yes/no): Assessed 

using 13-item self-administered 

headache questionnaire in TBI clinic. 

Chronic daily headaches (CDH; defined 

as headaches occurring ≥15 days per 

month for the previous 3 months); 

episodic headaches were<15 

days/month. Also measured headaches 

meeting criteria for migraine, posttraumatic headache (PTHA), and 

headaches that disrupt functioning. 

Total headache: 957/978 

(97.9%)

CDH: 196/978 (20.0%)

Episodic headache: 761/978 

(77.8%)

Migraine: 504/978 (51.5%)

PTHA: 360/978 (36.8%)

Disrupt functioning: 397/978 

(40.6%)

Jackson, 

201648

n=612

Post-9/11 

Veterans.

EHR 

data/Selfreport

Headache presence (yes/no): Assessed 

as part of the VA TBI Clinical Reminder 

and Screening Tool (endorsed 

symptoms after injury and currently).

Total mTBI: 196/592 (33.1%)

mTBI+PTSD: 151/384 

(39.3%)

mTBI no PTSD: 45/208 

(21.6%)

Wilk, 201060

n=587

Post-9/11 SMs.

PHQ-15 Headache presence in past month

(yes/no): “Bothered a lot”=yes.

Total mTBI: 144/563 (25.6%)

LOC: 72/197 (36.5%)

AOC: 72/366 (19.7%)

Schwab, 201751

n=557

Post-9/11 SMs.

NSI Headache intensity: Proportion that

rated item on the NSI for headaches as 

a 3 or 4 (severe or very severe) on a 0-

4 scale, 3-months post-deployment 

(and post-TBI screening).

15% of 358 who completed 

3-month follow-up.

King, 201440

n=421

Post-9/11

Veterans. 

EHR data Headache presence (yes/no): If treated 

for headache conditions for ≥3 months

based on ICD diagnosis codes (ie, if the 

time elapsed between encounters with 

similarly coded conditions was ≥90 

days from the initial encounter).

Total mTBI:

160/421 (38.0%)

mTBI+PTSD:

145/283 (51.2%)

Walker, 

2018a57

n=414 

Post-9/11 

Veterans/SMs.

CENC sample. 

HIT-6 Headache impact on function, 

categorized as: No headaches lately; 

Little to no impact; Some impact; 

Substantial impact; Very severe impact. 

Some impact: 

44/407 (10.8%) 

Substantial impact: 

50/407 (12.3%) 

Very severe impact: 172/407

(42.3%)

Some to very severe 

headache impact: 266/407 

(65.4%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Headache presence in past month

(yes/no): “Bothered a lot”=yes.

Total mTBI: 84/375 (22.4%)

LOC: 39/121 (32.2%) 

AOC: 45/254 (17.7%)
Chronic Pain and mTBI Evidence Synthesis Program

44

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details 

of assessment tool 

Prevalence Results 

n (%) 

Romesser, 

201244

n=354

Post-9/11 

Veterans

assessed at 2 

polytrauma 

clinics.

Self-report Headache presence (yes/no): If Veteran 

reported problems with pain in the past 

30 days, self-reported information about 

pain characteristics was used to classify 

the individual with head

pain/headaches. 

Total mTBI: 266/354 (75.1%)

LOC: 116/144 (80.6%)

No LOC: 150/210 (75.1%) 

MacGregor, 

201349

n=334

Post-9/11 SMs.

PDHRA Headache presence (yes/no): Asked to 

endorse whether they currently have 

headache pain that they feel is related 

to their deployment. 

Total mTBI: 111/334 (33.2%)

mTBI with LOC: 37/103 

(35.9%)

mTBI no LOC: 43/150 

(28.7%)

Vanderploeg, 

200956

n=278

Vietnam-era 

Veterans.

Self-report Headache presence (yes/no): Medical 

history interview and questionnaire: 

“During the past year, have you had 

unusually frequent or severe 

headaches?”.

27.0%

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Headache presence in past month

(yes/no): “Bothered a lot”=yes.

Total mTBI: 85/260 (32.7%)

LOC: 40/86 (46.5%) 

AOC: 45/174 (25.9%)

mTBI+PTSD: 53/96 (55.2%)

mTBI no PTSD: 31/163 

(19.0%)

Patil, 201150

n=246

Post-9/11 

Veterans seen 

in Polytrauma 

clinic.

CTBIE and 

EHR

Headache presence (yes/no): Asked if 

they experienced headache pain within 

the 30 days preceding the CTBIE. 

Among Veterans who were referred to 

and attended a Neurology clinic 

evaluation, diagnoses of migraine, 

chronic daily headache (CDH), and 

post-traumatic headache (PTHA) were 

measured.

CTBIE: 182/246 (74.0%)

Received and attended 

Neurology clinic referral: 

56/246 (22.8%)

Migraine: 25/56 (44.6%)

CDH: 11/56 (19.6%)

PTHA: 4/56 (7.1%)

Brickell, 201442

n=167

Post-9/11 SMs.

Telephone 

interview 

with openended 

questions

Headache presence (yes/no): Any in 

past month. (the telephone follow-up 

interview is an unpublished, 10-15 min,

semi-structured interview developed 

specifically for this study.) 

6 mos: 73.9%

12 mos: 67.4%

24 mos: 85.2%

36 mos: 83.3%

48 mos: 83.3%

60 mos: 92.0%

Headache frequency: Daily or weekly in 

past month. 

6 mos: 58.7%

12 mos: 56.2%

24 mos: 64.8%

36 mos: 64.3%

48 mos: 70.0%

60 mos: 76.0%
Chronic Pain and mTBI Evidence Synthesis Program

45

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details 

of assessment tool 

Prevalence Results 

n (%) 

Headache intensity: Moderate or higher

in past month.

6 mos: 52.2%

12 mos: 41.6%

24 mos: 53.7%

36 mos: 59.5%

48 mos: 63.3%

60 mos: 68.0%

Pain location: Any (non-headache) 

head or neck pain in past month. 

6 mos: 17.4%

12 mos: 18.0%

24 mos: 16.7%

36 mos: 7.1%

48 mos: 20.0%

60 mos: 4.0%

Ruff, 20086

n=126

Post-9/11 

Veterans seen 

in a polytrauma 

clinic.

Neurological 

exam

Headache presence (yes/no): Present 

and associated with Post-9/11

deployment. Among Veterans with 

headache, proportions with diagnoses 

of migraine, tension, or mixed 

headache presented.

Any headache: 80/126 

(63.5%)

Migraine: 14/126 (11.1%)

Tension: 36/126 (28.6%)

Mixed: 30/126 (23.8%) 

Couch, 201646

n=43

Post-9/11 

Veterans.

Self-report 

during 

clinical 

assessment

Headache frequency: Chronic daily 

headaches (CDH; defined as ≥15 

days/month) or frequent headaches

(defined as 10-14 days/month) in 6 

months prior to telephone 

questionnaire. (Used detailed headache 

questionnaire which has been used in 

the University of Oklahoma Headache

Clinic since 1996.)

All mTBI:

CDH: 18/43 (41.9%)

Frequent headache: 16/43 

(37.2%)

Either CDH or FH: 34/43 

(79.1%) 

mTBI with LOC:

CDH: 11/23 (47.8%)

Frequent headache: 6/23 

(26.1%)

mTBI with AOC:

CDH: 7/20 (35.0%)

Frequent headache:

10/20 (50.0%)

Self-report 

during 

clinical 

assessment.

Tension headache presence (yes/no): 

Determined by headache questionnaire 

and based on the hierarchical method 

of the ICDH-3 system. 

All mTBI: 4/43 (9.3%)

mTBI with LOC: 2/23 (8.7%)

mTBI with AOC: 2/20 (10.0%)

Self-report 

during 

clinical 

assessment.

Migraine (with & without aura) presence

(yes/no): Determined by headache 

questionnaire and based on the 

hierarchical method of the ICDH-3 

system.

All mTBI: 38/43 (88.4%)

mTBI with LOC: 21/23 

(91.3%)

mTBI with AOC: 17/20 

(85.0%)

FarrellCarnahan, 

201547

N=40

VA PRC 

TBIMS.

NSI Headache intensity: NSI Item 4 

‘severely’/‘very severely’ disturbed by 

headaches in the last 2 weeks.

11/40 (27.5%)

Abbreviations: AOC=Alteration of consciousness; CDH=Chronic daily headaches; EHR=Electronic Health Record; 

FH=Frequent headaches; HIT-6=Headache Impact Test; ICDH-3=The International Classification of Headache 
Chronic Pain and mTBI Evidence Synthesis Program

46

Disorders 3rd edition; LOC=Loss of consciousness; mTBI=Mild Traumatic Brain Injury; NSI=Neurobehavioral 

Symptom Inventory; OEF=Operation Enduring Freedom; OIF=Operation Iraqi Freedom; PDHRA=PostDeployment Health Re-Assessment; PHQ-15=15-item Patient Health Questionnaire scale; PRC=Polytrauma 

Rehabilitation Center; PTHA=Posttraumatic headaches; SM=Servicemember; TBI=Traumatic Brain Injury; 

TBIMS=Traumatic Brain Injury Model Systems; VA=Veterans Affairs; VALOR=Veterans' After-discharge 

Longitudinal Registry

Back pain

We included 10 studies that reported measures of back pain prevalence among Veterans and SMs 

with mTBI.7,15,40,44,49,52,53,56,59,60 These studies ranged in size from clinical samples of 260 to large 

database studies of 93,003. Pain assessment varied broadly across studies and included validated 

measures of pain presence, standardized measures used in surveillance and screening 

instruments, and ICD diagnosis codes from healthcare records.

Three studies involved similar Post-9/11 SM populations and methodology, including 

assessment of pain using the PHQ-15, and may provide the most consistent evidence for 

prevalence of chronic back pain.

15,59,60 Prevalence levels of back pain among SMs with mTBI in 

these 3 studies ranged from 32% to 44%. These studies also reported prevalence levels stratified 

by mTBI with loss of consciousness (LOC) versus alteration of consciousness (AOC); the 

prevalence of back pain was consistently higher among those with LOC than those with AOC, 

but only slightly so. Wilk et al, 201259 also stratified prevalence levels by mTBI with, versus 

without, comorbid PTSD and prevalence of back pain was considerably higher among those with 

comorbid PTSD (56% versus 36%).

Using data from the VA CTBIE, which asks about pain in the past 30 days, 2 studies by Suri et 

al52,53 also report relatively consistent findings. In these 2 samples, 13%52 and 16%53 of Veterans 

with mTBI reported the presence of upper back pain (versus 11%, in both studies, among those 

without confirmed mTBI) and 53%52 and 58%53 reported the presence of lower back pain (versus 

48%, in both studies, of those without confirmed mTBI). Romesser et al reported somewhat 

similar, although higher, figures for a sample of Post-9/11 Veterans treated at 2 polytrauma 

clinics.44 Based on a clinical questionnaire used with these treatment-seeking Veterans, 21% 

experienced upper back pain and 61% experienced lower back pain. This compared to 13% and 

56% among those who did not have a history of mTBI.

Two studies were based on VA EHR data and reported prevalence of back pain diagnoses among 

Post-9/11 Veterans.

7,40 Pugh et al used data for only the first year of Veterans’ VA use and 

reported a prevalence of 27% among 93,003 Veterans with mTBI (compared to 18% among 

Veterans without any indication of mTBI history).

7 King et al used data for multiple years of VA 

use and reported a prevalence of 46% among 421 Veterans with mTBI history (versus 23% of 

those without).

40

Additional details of these and other studies presenting back pain data are presented in Table 5.

Neck pain

Five studies reported data on prevalence of neck pain among Veterans with mTBI; all 5 involved 

Post-9/11 VA patients.7,40,44,52,53 Two studies were based on VA EHR data and reported 

prevalence of neck pain diagnoses.7,40 Pugh et al used data for only the first year of Veterans’ 
Chronic Pain and mTBI Evidence Synthesis Program

47

VA use and reported a prevalence of 6% among 93,003 Veterans with mTBI history (and 3% 

among 434,378 Veterans without mTBI),

7 while King et al used data for multiple years of VA 

use and reported a prevalence of 14% among 421 Veterans (and 6% among a matched sample of 

421 Veterans without mTBI).

40 Two studies by Suri et al52,53 used data from the VA CTBIE, 

which asks about pain in the past 30 days. In these 2 samples, 23%52 and 30%53 of those with 

clinician-confirmed mTBI reported the presence of neck pain, while only 19% and 21% of those

without clinician-confirmed mTBI reported neck pain. The highest prevalence of neck pain was 

observed in a sample of 354 Veterans seeking care in VA polytrauma clinics,44 in which 40% 

reported that they had experienced neck pain in the past 30 days on a clinical questionnaire (45% 

among those who experienced LOC with their mTBI and 37% among those who did not; in 

comparison, 29% of Veterans without mTBI history reported neck pain).

Arm, leg, and/or joint pain 

Arm, leg and/or joint pain were reported in 9 studies.

15,39,42,49,52,53,56,59,60 Outcomes were assessed 

differently across studies, both in terms of what qualified as chronic arm, leg, or joint pain and 

the specific parts of the arms, legs, and/or joints that the studies assessed. 

The largest study involved 32,316 Post-9/11 Veterans and used 1 year of VA EHR data to 

estimate prevalence of musculoskeletal pain among patients with mTBI.

39 Almost 39% of 

Veterans diagnosed with mTBI were diagnosed with musculoskeletal pain; among Veterans 

diagnosed with both mTBI and PTSD, 47% were also diagnosed with musculoskeletal pain

(versus 35% of those with PTSD diagnoses only). This study defined both mTBI and pain (and 

PTSD) as any single instance of a respective ICD diagnosis code in the Veterans’ health record. 

Three studies15,59,60 assessed pain using the PHQ-15, which asks about “Arm/leg/joint pain” 

intensity in the past month. For the purposes of these studies, those who ranked their pain 

intensity as "bothered a lot" were considered to have chronic pain. All 3 studies reported 

prevalence levels of arm/leg/joint pain between 40% and 50%. These studies stratified the mTBI 

sample by those who had experienced an LOC at the time of their mTBI versus those who 

experienced AOC.

15,59,60 In 2 of the studies,59,60 prevalence estimates were slightly higher for 

those with LOC versus those with AOC; the opposite was observed in the third study.

15 One 

study also stratified the sample by whether comorbid PTSD was present.59 As with other types of 

chronic pain, reports of arm/leg/joint pain were considerably more prevalent among those with

comorbid PTSD than among those without (66% and 41%, respectively).

Two large studies using CTBIE data reported on “other joint pain,” defined as pain experienced 

in the legs, arms, hands, feet, or "other" locations in the past 30 days.52,53 Prevalence levels in 

these studies were fairly similar for those with clinician-confirmed mTBI (48% and 53%), with 

both estimates slightly higher than among those without confirmed mTBI (44% and 43%). These

2 studies also reported on shoulder pain and, again, presented similar results (25% and 30%, 

versus 21% and 22%).

Several smaller studies reported on pain in various joints and parts of the arms and legs (eg, 

shoulders, knees, hips). See Table 5 for details of pain measurement and prevalence outcomes in 

these and all other included studies.
Chronic Pain and mTBI Evidence Synthesis Program

48

Abdominal/stomach pain

Five studies reported prevalence of abdominal or stomach pain among Veterans and SMs with 

mTBI.

15,40,56,59,60 All reported prevalence levels that were, in general, 10% or less. Among these 

studies, 3 involved similar Post-9/11 SM study populations and methodology;

15,59,60 prevalence 

ranged from 7% to 9% (these estimates were slightly higher than those provided in the 2 studies 

that also reported prevalence among participants without mTBI). These studies also reported 

prevalence stratified by mTBI with LOC versus mTBI with AOC and, in general, abdominal pain 

prevalence was slightly higher among those with LOC versus AOC. A study by Wilk et al59 also 

stratified prevalence levels by mTBI with, versus without, comorbid PTSD and prevalence was 

considerably higher among those with comorbid PTSD (12% versus 5%). Another study 

examined VA healthcare records for Post-9/11 Veterans 40 and reported that 3% of those 

diagnosed with post-concussion syndrome had also been diagnosed with abdominal pain. 

Finally, a 1980s study of Vietnam-era Veterans reported abdominal pain in 10% of those with a 

history of mTBI (versus 12% among those with other injuries but without mTBI).

56

Arthritis 

Two studies reported prevalence of arthritis (considered an indicator of chronic pain) among 

individuals with mTBI.40,57 Both were smaller studies with similar sample sizes, 41457 and 421,

40

and reported fairly consistent prevalence estimates of 44% and 41% respectively. These 

estimates were higher than estimates among participants in these studies without mTBI (30% and 

33%, respectively). The smaller study used CENC data for prevalence of arthritis,

57 and the 

larger used VA EHR data to estimate the presence of arthritis for at least 3 months.40

Chest pain

Three studies involving similar Post-9/11 SM study populations and methodology reported on 

chest pain.

15,59,60 Prevalence levels among SMs with mTBI in these 3 studies ranged from 6% to 

12%. Two studies included estimates for comparison groups with other (non-mTBI) injuries (4% 

and 5%) or with no injuries (4% and 2%). These studies also reported prevalence levels stratified 

by mTBI with LOC versus AOC; as reported above, the prevalence of chest pain was 

consistently slightly higher among those with LOC than those with AOC. Wilk et al, 201259 also 

stratified prevalence levels by mTBI with, versus without, comorbid PTSD and prevalence was 2 

times higher among those with comorbid PTSD (19% versus 8%).

Pain medication use

Use of pain medications, abstracted as an indicator of chronic pain, was reported in 4 articles.

40-

42,54 Three studies were clinic-based and enrolled Post-9/11 Veterans/SMs,41,42,54 while the other

study was based on EHR data for Post-9/11 Veterans.

40 In an analysis of CENC study data, Hoot 

et al41 reported that 50% of 379 participants with mTBI were using analgesic pain medications, 

compared to 32% of those without a history of mTBI. Brickell et al42 queried 167 Post-9/11 SMs 

with mTBI and polytrauma who participated in follow-up telephone interviews. Among the 46 

participants interviewed within 6 months of their injury, 30% reported using prescription opioid

medications and 100% reported using non-opioid pain medications. Finally, in a clinical study of 

978 SMs who screened positive for mTBI and were evaluated in a TBI program,

54 50% of the 

196 with chronic daily headaches (and 11.6% of the entire mTBI sample) reported using abortive 

headache medications for 15 or more days per month in the prior 3 months. A study based on 
Chronic Pain and mTBI Evidence Synthesis Program

49

VA EHR data for Post-9/11 Veterans with diagnosed post-concussion syndrome in the Northeast 

region of the US reported that 78% had received any kind of pain control prescription 

medication; 49% were prescribed opioid analgesics, 29% non-opioid analgesics, 58% nonsteroidal anti-inflammatory drugs (NSAIDs), and 17% anti-migraine agents.40 This study also 

stratified medication receipt by comorbid PTSD diagnosis status and, with the exception of 

NSAID medications, pain medication prescriptions were more prevalent among Veterans with 

comorbid PTSD than those without. 

Sexual pain/problems

The 3 studies involving similar Post-9/11 SM study populations and methodology also reported 

on sexual pain/problems.15,59,60 The prevalence levels among SMs with mTBI in these studies 

ranged from 5% to 9%. These estimates were slightly higher than those from the 2 studies that 

provided an injured (but no mTBI) comparison group (5% and 4%) and a non-injured (2% and 

1%) comparison group. These studies also reported prevalence levels stratified by mTBI with 

LOC versus AOC and, again, the prevalence of sexual pain/problems was consistently slightly 

higher among those with LOC than those with AOC. Wilk et al 201259 also stratified prevalence 

levels by mTBI with, versus without, comorbid PTSD and prevalence was considerably higher 

among those with comorbid PTSD (22% versus 3%). Of note, the vast majority (91% to 99%) of 

participants in these 3 studies were male.

Other pain

A small number of studies reported other pain types not otherwise categorized above.7,39,40,42

Data from these studies are presented in Table 5. 

Table 5. Prevalence estimates of other chronic pain from studies of Veterans and 

Servicemembers with a history of mTBI

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

Back Pain

Pugh, 20197

n=93,003

Veterans.

EHR data Back pain presence (yes/no): ICD diagnosis 

code in health record during first year of VA 

care.

25,255/93,003 (27.2%) 

Suri, 201952

n=23,703

Post-9/11 

Veterans.

EHR data Back pain presence (yes/no): VA health care 

use for back pain in past year. 

8,661/23,703 (36.5%)

CTBIE Back pain presence (yes/no): Indicate whether 

experienced in last 30 days.

13,303/23,703 (56.1%)

Low back pain (yes/no) 12,498/23,703 (52.7%)

Upper back pain (yes/no) 3,162/23,703 (13.3%)

Suri, 201753

n=1,683

Post-9/11 

Veterans.

CTBIE Back pain presence (yes/no): Indicate whether 

experienced in last 30 days.

60.9%

Low back pain (yes/no) 57.5%

Upper back pain (yes/no) 15.6%

Wilk, 201060

n=587

PHQ-15 Back pain presence in past month (yes/no): 

“Bothered a lot”=yes.

Total mTBI: 205/562

(36.5%)
Chronic Pain and mTBI Evidence Synthesis Program

50

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

Post-9/11 SMs. LOC: 85/197 (43.1%)

AOC: 120/365 (32.8%)

King, 201440

n=421

Post-9/11

Veterans. 

EHR data Back pain presence (yes/no): If treated for 

back pain conditions for ≥3 months based on 

ICD diagnosis codes (ie, if the time elapsed 

between encounters with similarly coded 

conditions was ≥90 days from the initial 

encounter).

Total mTBI: 193/421 

(45.8%)

mTBI+PTSD: 170/283 

(60.1%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Back pain presence in past month (yes/no): 

“Bothered a lot”=yes.

Total mTBI: 118/374 

(31.6%)

LOC: 40/121 (33.1%) 

AOC: 78/253 (30.8%)

Romesser, 

201244

n=354

Post-9/11 

Veterans 

assessed at 2 

polytrauma 

clinics.

Self-report Low back pain presence (yes/no): If Veteran 

reported problems with pain in the past 30 

days, self-reported information about pain 

characteristics was used to classify the 

individual with low back pain.

Total mTBI: 216/354

(61.0%)

LOC: 90/144 (62.5%)

No LOC: 126/210 

(60.0%)

Upper back pain presence (yes/no): Same as 

above.

Total mTBI: 73/354

(20.6%)

LOC: 34/144 (23.6%)

No LOC: 39/210 

(18.6%)

MacGregor, 

201349

n=334

Post-9/11 SMs. 

PDHRA Back pain presence (yes/no): Asked to 

endorse whether they currently have pain that 

they feel is related to their deployment. 

Total mTBI: 110/334

(32.9%)

mTBI with LOC: 31/103 

(30.1%)

mTBI no LOC: 49/150 

(32.7%)

Vanderploeg, 

200956

n=278

Vietnam-era 

Veterans.

Self-report Low back pain presence (yes/no): Unusually 

frequent or severe pain during last year via 

medical history interview and questionnaire.

36.3% 

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Back pain presence in past month (yes/no): 

“Bothered a lot”=yes.

Total mTBI: 114/260 

(43.8%)

LOC: 39/86 (45.3%) 

AOC: 75/174 (43.1%)

mTBI+PTSD: 54/96 

(56.3%)

mTBI no PTSD: 59/163 

(36.2%)

Neck Pain

Pugh, 20197

n=93,003 Post9/11 Veterans.

EHR data Neck pain presence (yes/no): ICD diagnosis 

code in health record during first year of VA 

care.

5,916/93,003 (6.4%)

Suri, 201952

n=23,703

CTBIE Neck pain presence (yes/no): Indicate whether 

experienced in last 30 days.

5,428/23,703 (22.9%)
Chronic Pain and mTBI Evidence Synthesis Program

51

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

Post-9/11 

Veterans.

Suri, 201753

n=1,683

Post-9/11 

Veterans.

CTBIE Neck pain presence (yes/no): Indicate whether 

experienced in last 30 days. 

30.4%

King, 201440

n=421

Post-9/11

Veterans. 

EHR data Neck pain presence (yes/no): If treated for 

neck pain conditions for ≥3 months based on 

ICD diagnosis codes (ie, if the time elapsed 

between encounters with similarly coded 

conditions was ≥90 days from the initial 

encounter).

Total mTBI: 57/421 

(13.5%)

mTBI+PTSD: 50/283 

(17.7%)

Romesser, 

201244

n=354

Post-9/11 

Veterans 

assessed at 2 

polytrauma 

clinics.

Self-report Neck pain presence (yes/no): If Veteran 

reported problems with pain in the past 30 

days, self-reported information about pain 

characteristics was used to classify the 

individual with neck pain.

Total mTBI: 143/354

(40.4%)

LOC: 65/144 (45.1%)

No LOC: 78/210 

(37.1%)

Arm/leg/joint pain

Kulas, 201839

n=32,316

Post-9/11 

Veterans.

EHR data Musculoskeletal pain presence (yes/no): 

Presence/absence of ICD diagnosis code in 

EHR.

mTBI+PTSD: 47.0%

mTBI no PTSD: 38.8% 

Suri, 201952

n=23,703

Post-9/11 

Veterans. 

CTBIE Shoulder pain presence (yes/no): Indicate 

whether experienced in last 30 days.

5,799/23,703 (24.5%)

Other joint pain (legs, arms, hands, feet, or 

“other” location) presence (yes/no): Indicate 

whether experienced in last 30 days.

11,357/23,703 (47.9%)

Suri, 201753

n=1,683 Post9/11 Veterans.

CTBIE Shoulder pain presence (yes/no): Indicate 

whether experienced in last 30 days.

30.0%

Other joint pain (legs, arms, hands, feet, or 

“other” location) presence (yes/no): Indicate 

whether experienced in last 30 days.

53.1%

Wilk, 201060

n=587

Post-9/11 SMs.

PHQ-15 Arm/leg/joint pain presence in past month 

(yes/no): “Bothered a lot”=yes.

Total mTBI: 254/559

(45.4%)

LOC: 95/196 (48.5%)

AOC: 159/363 (43.8%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Arm/leg/joint pain presence in past month 

(yes/no): “Bothered a lot”=yes. 

Total mTBI: 150/373 

(40.2%)

LOC: 45/121 (37.2%) 

AOC: 105/252 (41.7%)

Vanderploeg, 

200956

n=278

Vietnam-era 

Veterans.

Self-report Calf pain presence (yes/no): Unusually 

frequent or severe pain during last year via 

medical history interview and questionnaire.

4.4%
Chronic Pain and mTBI Evidence Synthesis Program

52

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Arm/leg/joint pain presence in past month 

(yes/no): “Bothered a lot”=yes. 

Total mTBI: 129/260 

(49.6%)

LOC: 47/86 (54.7%)

AOC: 82/174 (47.1%)

mTBI+PTSD: 63/96 

(65.6%)

mTBI no PTSD: 66/163 

(40.5%)

Brickell, 201442

n=167

Post-9/11 SMs.

Telephone 

interview 

with openended 

questions.

Lower extremities pain (yes/no): Any pain in 

past month (the telephone follow-up interview

is an unpublished, 10-15 min, semi-structured 

interview developed specifically for this study). 

6 mos: 43.5%

12 mos: 37.1%

24 mos: 55.6%

36 mos: 28.6%

48 mos: 23.3%

60 mos: 28.0%

Upper extremities pain (yes/no). 6 mos: 26.1%

12 mos: 24.7%

24 mos: 25.9%

36 mos: 19.0%

48 mos: 23.3%

60 mos: 8.0%

MacGregor, 

201349

n=334

Post-9/11 SMs.

PDHRA Joint and muscle pain presence (yes/no): 

Asked to endorse whether they currently have 

pain that they feel is related to their 

deployment. 

Total mTBI:

78/334 (23.4%)

mTBI with LOC:

25/103 (24.3%)

mTBI no LOC:

49/150 (32.7%)

Abdominal/stomach pain

Vanderploeg, 

200956

n=278

Vietnam-era 

Veterans.

Self-report Abdominal pain presence (yes/no): Unusually 

frequent or severe pain during last year via 

medical history interview and questionnaire.

10.1%

40

n=421

Post-9/11

Veterans. 

EHR data Abdominal pain presence (yes/no): If treated 

for abdominal pain conditions for ≥3 months

based on ICD diagnosis codes (ie, if the time 

elapsed between encounters with similarly 

coded conditions was ≥90 days from the initial 

encounter).

Total mTBI: 12/421 

(2.9%)

mTBI+PTSD: 11/283 

(3.9%)

Wilk, 201060

n=587

Post-9/11 SMs.

PHQ-15 Stomach pain presence in past month

(yes/no): “Bothered a lot”=yes.

Total mTBI: 47/557 

(8.4%)

LOC: 17/196 (8.7%)

AOC: 30/361 (8.3%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Stomach pain presence in past month 

(yes/no): “Bothered a lot”=yes. 

Total mTBI: 34/369 

(9.2%)

LOC: 14/120 (11.7%) 

AOC: 20/249 (8.0%)

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Stomach pain presence in past month 

(yes/no): “Bothered a lot”=yes. 

Total mTBI: 19/260 

(7.3%)

LOC: 5/86 (5.8%)
Chronic Pain and mTBI Evidence Synthesis Program

53

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

AOC: 14/174 (8.0%)

mTBI+PTSD: 11/96 

(11.5%)

mTBI no PTSD: 8/163 

(4.9%)

Arthritis

King, 201440

n=421

Post-9/11 

Veterans.

EHR Arthritis presence (yes/no): If treated for 

arthritis conditions for ≥3 months based on ICD 

diagnosis codes (ie, if the time elapsed 

between encounters with similarly coded 

conditions was ≥90 days from the initial 

encounter).

Total mTBI: 173/421 

(41.1%)

mTBI+PTSD: 152/283 

(53.7%)

Walker, 

2018a57

n=414 

Post-9/11 

Veterans/SMs.

CENC sample

BRFSS Arthritis presence (yes/no): This item was 

asked as in the CDC’s Behavioral Risk Factor 

Surveillance System: “Has a doctor, nurse, or 

other health professional EVER told you that 

you had any of the following? For each, tell me 

‘Yes,’ ‘No,’ or you’re ‘Not sure.’” Variable was 

dichotomous.

180/412 (43.7%)

Chest Pain

Wilk, 201060

n=587

Post-9/11 SMs.

PHQ-15 Chest pain presence in past month (yes/no): 

“Bothered a lot”=yes. 

Total mTBI: 46/560

(8.2%)

LOC: 28/196 (14.3%)

AOC: 18/364 (4.9%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Chest pain presence in past month (yes/no): 

“Bothered a lot”=yes. 

Total mTBI: 24/374 

(6.4%)

LOC: 17/121 (14.0%)

AOC: 7/253 (2.8%)

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Chest pain presence in past month (yes/no): 

“Bothered a lot”=yes. 

Total mTBI: 30/260 

(11.5%)

LOC: 11/86 (12.8%)

AOC: 19/174 (10.9%)

mTBI+PTSD: 18/96 

(18.8%)

mTBI no PTSD: 13/163 

(8.0%)

Pain medication use

Theeler, 2012 

54

n=978

Post-9/11 SMs.

Self-report Abortive headache medication use among 

those with chronic daily headaches (CDH; ≥15 

days/month for past 3 months; n=196) versus 

those with episodic headaches (<15 

days/month; n=761).

Total mTBI: 113/978 

(11.6%) 

CDH: 97/196 (49.5%)

Episodic headache: 

16/761 (2.1%)

King, 201440

n=421

Post-9/11 

Veterans.

EHR data Any pain control medication prescriptions 

identified in VA pharmacy records (yes/no).

Total mTBI: 312/400 

(78.0%)

TBI+PTSD: 277/351 

(78.9%)

TBI no PTSD: 35/49 

(71.4%)
Chronic Pain and mTBI Evidence Synthesis Program

54

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

Opioid analgesic prescriptions identified in VA 

pharmacy records (yes/no).

Total mTBI: 195/400 

(48.8%)

TBI+PTSD: 174/351 

(49.6%)

TBI no PTSD: 21/49 

(42.9%)

Non-opioid analgesics prescriptions identified 

in VA pharmacy records (yes/no).

Total mTBI: 117/400 

(29.3%)

TBI+PTSD: 104/351 

(29.6%)

TBI no PTSD: 13/49 

(26.5%)

Non-steriodal anti-inflamatory drug 

prescriptions identified in VA pharmacy records 

(yes/no).

Total mTBI: 231/400 

(57.8%)

TBI+PTSD: 103/351 

(29.3%)

TBI no PTSD: 29/49 

(59.2%)

Anti-migraine agent prescriptions identified in 

VA pharmacy records (yes/no).

Total mTBI:

66/400 (16.5%)

TBI+PTSD: 59/351 

(16.8%)

TBI no PTSD: 7/49 

(14.3%)

Hoot, 201841

n=379

Post-9/11 

Veterans/SMs.

CENC sample

EHR/SelfreportAnalgesic medication use (yes/no): Uses 

analgesic medications. 

188/376 (50.0%)

Brickell, 201442

n=167

Post-9/11 SMs.

Telephone 

interview 

with openended 

questions 

Opioid pain medication use (yes/no): Asked if 

taking any medications and categorized post 

hoc. The telephone follow-up interview is an 

unpublished, 10-15 min, semi-structured 

interview developed specifically for this study.

6 mos: 30.4%

12 mos: 25.8%

24 mos: 18.5%

36 mos: 19.0%

48 mos: 26.7%

60 mos: 12.0%

Other (non-opioid) pain medication use 

(yes/no): Asked if taking any medications for 

pain and categorized post hoc.

6 mos: 100%

12 mos: 27.0%

24 mos: 18.5%

36 mos: 19.0%

48 mos 30.0%

60 mos: 8.0%

Sexual pain/problems

Wilk, 201060

n=587

Post-9/11 SMs.

PHQ-15 Sexual pain/problems presence in past month

(yes/no): “Bothered a lot”=yes. 

Total mTBI: 33/560

(5.9%)

LOC: 16/196 (8.2%)

AOC: 17/364 (4.7%)

Hoge, 200815

n=384

Post-9/11 SMs.

PHQ-15 Sexual pain/problems presence in past month

(yes/no): "Bothered a lot"=yes. 

Total mTBI: 18/373 

(4.8%)

LOC: 10/120 (8.3%)
Chronic Pain and mTBI Evidence Synthesis Program

55

Author, year

N pts with 

mTBI

Population

Pain 

assessed 

by

Pain measurement definition/details of 

assessment tool

Prevalence Results 

n (%)

AOC: 8/253 (3.2%)

Wilk, 201259

n=260

Post-9/11 SMs.

PHQ-15 Sexual pain/problems presence in past month

(yes/no): "Bothered a lot"=yes. 

Total mTBI: 23/260 

(8.8%)

LOC: 9/86 (10.5%)

AOC: 14/174 (8.0%)

mTBI+PTSD: 21/96 

(21.9%)

mTBI no PTSD: 4/163 

(2.5%)

Other

Kulas, 201839

n=32,316

Post-9/11 

Veterans.

EHR data Skeletal pain presence (yes/no): 

Presence/absence of ICD diagnosis code in 

EHR.

mTBI+PTSD: 3.1%

mTBI no PTSD: 2.1%

Diabetic pain presence (yes/no): 

Presence/absence of ICD diagnosis code in 

EHR.

mTBI+PTSD: 0.3%

mTBI no PTSD: 0.2%

Fibromyalgia presence (yes/no): 

Presence/absence of ICD diagnosis code in 

EHR.

mTBI+PTSD: 4.1%

mTBI no PTSD:2.2%

Herpetic pain presence (yes/no): 

Presence/absence of ICD diagnosis code in 

EHR.

mTBI+PTSD: 1.1%

mTBI no PTSD: 0.6%

Pugh, 20197

n=93,003 

Post-9/11

Veterans.

EHR data Other pain presence (arthritis/musculoskeletal 

pain; yes/no): ICD diagnosis code in health 

record during first year of VA care. 

19,631/93,003 (21.1%)

King, 201440

n=421

Post-9/11 

Veterans.

EHR data Other pain presence (yes/no): If treated for 

other pain conditions for ≥3 months based on 

ICD diagnosis codes (ie, if the time elapsed 

between encounters with similarly coded 

conditions was ≥90 days from the initial 

encounter).

Total mTBI: 107/421

(25.4%)

mTBI+PTSD: 99/283 

(35.0%)

Brickell, 201442

n=167

Post-9/11 SMs.

Telephone 

interview 

with openended 

questions

Body pain (as contrasted with extremities and 

head and neck pain) presence (yes/no): Any 

pain in past month

(the telephone follow-up interview is an 

unpublished, 10-15 min, semi-structured 

interview developed specifically for this study).

6 mos: 43.5%

12 mos: 40.4%

24 mos: 37.0%

36 mos: 38.1%

48 mos: 40.0%

60 mos: 16.0%

Abbreviations: AOC=Alteration of consciousness; BRFSS=Behavioral Risk Factor Surveillance System; 

CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; ICD=International Classification of 

Diseases; LOC=Loss of consciousness; PDHRA=Post-Deployment Health Re-Assessment; PHQ-15=15-item 

Patient Health Questionnaire scale; PTSD=Posttraumatic stress disorder; SM=Servicemember; VA=Veterans 

Affairs
Chronic Pain and mTBI Evidence Synthesis Program

56

KQ1a. What are the most common types of chronic pain in US Veterans or 

Servicemembers with a history of mTBI?

Across studies, back pain, head pain, and arm, leg, and/or joint pain were the most prevalent 

types of chronic pain observed. For instance, 1 study of 384 SMs with a history of mTBI15 asked 

how much they were bothered by physical symptoms in the past month (PHQ-15) including 

stomach pain, back pain, arm, leg, or joint pain, headache, and chest pain. Of those with a history 

of mTBI, arm, leg, or joint pain was the most prevalent (40.2% indicated they were “bothered a 

lot”), followed by back pain (31.6%), then headache (22.4%). See Table 4 and Table 5 for more 

details.

KQ1b. Do the prevalence or types of chronic pain experienced by US Veterans or 

Servicemembers with a history of mTBI differ by mTBI etiology?

Three studies41,46,60 provide evidence for prevalence of chronic pain in Veterans and SMs with a 

history of mTBI by mTBI etiology. Table 6 summarizes the results of these studies. All included 

studies examined mTBI due to blast compared to mTBI resulting from non-blast causes; no other 

etiologies were examined/compared. Overall, blast-related mTBI did not appear to be associated 

with more frequent or more severe pain in these 3 studies. One exception was the measure of 

headache prevalence in Wilk et al 201060 which, among Veterans who experienced LOC after 

their mTBI (but not those who only experienced AOC), was endorsed for 40% of those whose 

mTBI was associated with blasts versus only 23% of those whose mTBI was not associated with 

blasts. None of the other pain types assessed in this study differed by mTBI etiology. The study 

by Hoot et al41 may also suggest higher pain prevalence among those with blast versus non-blast 

mTBI; however, this difference was small (eg, 63% versus 56%). None of the studies compared 

pain prevalence levels by location of mTBI, location of co-occurring injuries, or timing of pain 

onset relative to the mTBI. 
Chronic Pain and mTBI Evidence Synthesis Program

57

Table 6. Prevalence of Chronic Pain in Veterans and Servicemembers with a History of mTBI by mTBI Etiology

Author, year

N pts with 

mTBI

Population

mTBI 

etiology 

assessed 

by

mTBI etiology 

measurement/

assessment tool

Pain 

assessed 

by

Pain measurement 

definition/details of 

assessment tool 

Pain prevalence results by etiology

n (%)

Wilk, 201060

n=587

Post-9/11 SMs.

Self-report The questionnaire (3-6 

months after return from 

deployment) asked soldiers 

whether they had been 

injured during deployment 

by a blast/explosion. 

PHQ-15 Stomach pain presence in past 

month (yes/no): "Bothered a 

lot"=yes.

LOC blast vs non-blast: 13/156 (8.3%) 

vs 4/40 (10.0%); P=0.76

AOC blast vs non-blast: 14/254 (5.5%) 

vs 16/107 (15.0%); P=0.01

Back pain presence in past 

month (yes/no): "Bothered a 

lot"=yes. 

LOC blast vs non-blast: 71/157 

(45.2%) vs 14/40 (35.0%); P=0.29

AOC blast vs non-blast: 84/257 

(32.7%) vs 36/108 (33.3%); P=0.90

Arm/leg/joint pain presence in 

past month (yes/no): "Bothered 

a lot"=yes. 

LOC blast vs non-blast: 78/156 

(50.0%) vs 17/40 (42.5%); P=0.48 

AOC blast vs non-blast: 105/256 

(41.0%) vs 54/107 (50.5%); P=0.11

Headache presence in past 

month (yes/no): "Bothered a 

lot"=yes. 

LOC blast vs non-blast: 63/157 

(40.1%) vs 9/40 (22.5%); P=0.04

AOC blast vs non-blast: 53/258 

(20.5%) vs 19/108 (17.6%); P=0.57

Chest pain presence in past 

month (yes/no): "Bothered a 

lot"=yes. 

LOC blast vs non-blast: 23/156 

(14.7%) vs 5/40 (12.5%); P=0.81 

AOC blast vs non-blast: 12/258 (4.7%) 

vs 6/106 (5.7%); P=0.79

Abdominal pain presence in 

past month (yes/no): "Bothered 

a lot"=yes. 

LOC blast vs non-blast: 13/156 (8.3%)

vs 3/40 (7.5%); P=1.00

AOC blast vs non-blast: 13/257 (5.1%) 

vs 4/107 (3.7%); P=0.79
Chronic Pain and mTBI Evidence Synthesis Program

58

Author, year

N pts with 

mTBI

Population

mTBI 

etiology 

assessed 

by

mTBI etiology 

measurement/

assessment tool

Pain 

assessed 

by

Pain measurement 

definition/details of 

assessment tool 

Pain prevalence results by etiology

n (%)

Hoot, 201841

n=379

Post-9/11 

Veterans/SMs. 

CENC sample.

VCU rCDI Detailed structured

diagnostic TBI interview for 

blast or non-blast TBI.

EQ-5D-5L Pain presence and intensity: 

Moderate, severe, or extreme

level of pain or discomfort.

mTBI by blast exposure:

≥1 TBI from blast: 123/196 (62.8%)

TBI not from blast: 101/182 (55.5%)

Severity breakdown:

(≥1 TBI from blast vs TBI not from 

blast): 

Moderate pain or discomfort: 83/196 

(42.3%) vs 83/182 (45.6%)

Severe pain or discomfort: 37/196 

(18.9%) vs 17/182 (9.3%)

Extreme pain or discomfort: 3/196 

(1.5%) vs 1/182 (0.5%)

Couch, 201646

n=43

Post-9/11 

Veterans.

Self-report Screening questionnaire in 

TBI clinic: Mode of injury 

recorded including number 

of blast injuries versus 

blunt injury with no blast. 

Self-report Detailed headache 

questionnaire which has been

used in the University of 

Oklahoma Headache clinic 

since 1996: Assessed chronic 

daily headache (CDH, defined 

as ≥15 days/month) and 

frequent headache (defined as

10-14 days/month) in the last 6 

months prior to telephone 

contact (questionnaire).

CDH:

Blast mTBI: 15/34 (44.1%)

Blunt mTBI-only: 4/9 (44.4%)

Frequent headache:

Blast mTBI: 12/34 (35.3%)

Blunt mTBI-only: 3/9 (33.3%)

Abbreviations: AOC=Alteration of consciousness; CDH=Chronic daily headaches; EQ-5D-5L=EuroQol Group 5-dimension 5-level version quality-of-life;

LOC=Loss of consciousness; mTBI=Mild traumatic brain injury; PHQ-15=15-Item Patient Health Questionnaire; SM=Servicemember; TBI=Traumatic brain 

injury; VCU-rCDI=Virginia Commonwealth University retrospective Concussion Diagnostic Interview
Chronic Pain and mTBI Evidence Synthesis Program

59

KQ1c. How do estimates of the prevalence of chronic pain and mTBI in US Veterans or 

Servicemembers differ according to pain measurement methods or definitions?

Studies of pain prevalence in populations with a history of mTBI (ie, those included for KQ1) 

employed a wide variety of strategies to assess pain. These strategies include self-report, use of 

validated measures, diagnostic data abstraction from the EHR, and evaluation of medication use 

for pain. Within types of measures used, there was also variability, as some studies required a 

certain threshold of symptoms (such as endorsement of at least “bothered a lot” on the PHQ-15), 

whereas other studies identified pain regardless of the level of severity (such as “frequent 

headache” in the past month). There was also heterogeneity in strategies for identifying pain 

from the EHR; while some studies indicated pain was present if there was any diagnosis within a 

given time period, other studies required 2 or more of the same pain diagnosis at least 3 months 

apart (presumably to match the definition of chronic pain, which requires pain to be present for 3 

or more consecutive months). 

As summarized for KQ1, studies reported a broad range of pain prevalence estimates, even 

among those using similar assessment methodology. In general, studies relying on more 

comprehensive diagnostic assessment methods reported lower pain prevalence estimates than 

studies using self-report methods of pain assessment. For example, both Seal et al4

 and Kulas 

and Rosenheck39 extracted EHR data; however, Seal et al required 2 or more instances of the 

same diagnostic code, more than 90 days apart, whereas Kulas and Rosenheck reported 

prevalence based on a singular instance of a pain diagnosis. The different prevalence levels of 

any chronic pain identified were 59% (Seal et al, 2017) and 71% (Kulas and Rosenheck, 2018). 

Similarly, in studies of head pain, results derived from the EHR,7,40,45,48,58 which are based on 

diagnostic assessment, generally reported lower prevalence levels than studies that reported selfreport data.42,44,46,50,55 In 3 different studies using the same self-report measure (the PHQ-15) and 

same cut-point,15,59,60 the authors identified relatively similar pain prevalence levels across 

studies (eg, range of 7.3% to 9.2% with abdominal/stomach pain).

Figures 3-7 portray the range of prevalence estimates by study and tool for some of the most 

common types of chronic pain. Where severity or frequency data were available, the estimates in 

these figures reflect more severe pain (in some cases moderate or higher, in others severe to very 

severe pain), and more frequent pain (most studies that specified used a cutoff of 15 or more 

days per month in the case of headaches). Some studies also reported prevalence estimates for 

multiple time frames of follow-up (such as at 6-month intervals, or pain occurring at less than, 

versus greater than, 180 days post-injury). Where studies reported multiple time frames, we used 

the more recent in these figures in order to be more comparable to studies that only examined 

pain in the past 30 days or 3 months. 
Chronic Pain and mTBI Evidence Synthesis Program

60

Figure 3. Prevalence of general chronic pain in Veterans/Servicemembers with a history of 

mTBI by study and pain measurement tool 

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; EQ-5D-5L=EuroQol 

Group 5-Dimension 5-Level version

59%

71%

76%

82%

75%

70%

37%

38%

59%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Seal, 2017

Kulas, 2018

King, 2014

Lew, 2009

Seal, 2017

Romessor, 2012

Brickell, 2014

Powell, 2015

Hoot, 2018

Prevalence

Study

EHR CTBIE self-report Multiple EQ-5D-5L
Chronic Pain and mTBI Evidence Synthesis Program

61

Figure 4. Prevalence of head pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; HIT-6=6-Item Headache 

Impact Test; NSI=Neurobehavioral Symptom Inventory; PDHRA=Post-Deployment Health Re-Assessment; PHQ15=15-item Patient Health Questionnaire 

36%

15%

20%

3%

33%

38%

70%

82%

74%

58%

98%

75%

27%

74%

79%

52%

79%

15%

28%

26%

33%

22%

65%

33%

64%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Kulas, 2018

Beswick-Escanlar, 2016

Pugh, 2019

Webb, 2015

Jackson, 2016

King, 2014

Suri, 2019

Suri, 2017

Patil, 2011

Tsao, 2017

Theeler, 2012

Romesser, 2012

Vanderploeg, 2009

Patil, 2011

Couch, 2016

Brickell, 2014

Couch, 2016

Schwab, 2017

Farrell-Carnahan, 2015

Wilk, 2010

Wilk, 2012

Hoge, 2008

Walker, 2018a

Macgregor, 2013

Ruff, 2008

Prevalence

Study

EHR CTBIE self-report NSI PHQ-15 HIT-6 PDHRA Neurological exam
Chronic Pain and mTBI Evidence Synthesis Program

62

Figure 5. Prevalence of back pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; PDHRA=PostDeployment Health Re-Assessment; PHQ-15=15-item Patient Health Questionnaire

Figure 6. Prevalence of neck pain in Veterans/Servicemembers with a history of mTBI by 

study and pain measurement tool

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record

6%

14%

23%

30%

40%

0% 20% 40% 60% 80% 100%

Pugh, 2019

King, 2014

Suri, 2019

Suri, 2017

Romesser, 2012

Prevalence

Study

EHR CTBIE self-report
Chronic Pain and mTBI Evidence Synthesis Program

63

Figure 7. Prevalence of arm, leg, and/or joint pain in Veterans and Servicemembers with a 

history of mTBI by study and pain measurement tool

Abbreviations: CTBIE=Comprehensive TBI Evaluation; EHR=Electronic Health Record; PDHRA=PostDeployment Health Re-Assessment; PHQ-15=15-item Patient Health Questionnaire 

KEY QUESTION 2: What is the risk of suicide in US Veterans or 

Servicemembers with chronic pain and a history of mTBI?

Summary of Findings

We found 1 study7 that addressed KQ2. It also contributed evidence in KQ1. This study only 

provided data related to sub-question ‘a.’ 

a. How does the prevalence of suicide-related outcomes in US Veterans or 

Servicemembers with a history of mTBI and chronic pain compare to US Veterans or 

Servicemembers with no mTBI history and/or no chronic pain?

Pugh and colleagues classified Veterans in the study into a number of phenotypes. The 

Polytrauma phenotype was defined by consistently high comorbidities of mental health 

disorders, post-concussive symptoms, and pain throughout the study, and therefore we 

considered this group to represent Veterans in the study with chronic pain and history of mTBI. 

A second group of interest was the Moderately Healthy + Decline phenotype, characterized by a 

worsening of symptoms from years 1 to 5. The comparison group is a moderately healthy group 

of Veterans with a history of mTBI, characterized by “relatively low probabilities of back pain, 

other pain, mental health and sensory conditions compared to the base-rate in the population.”7

The prevalence of suicide-related behaviors (ie, suicidal ideation/attempt, identified based on 

ICD-9-CM diagnosis codes) in Veterans with mTBI classified in the Polytrauma phenotype 

(n=11,333) was 6.1% and in the Moderately Healthy + Decline phenotype (n=17,706) was 6.9%, 

compared to 2.9% in the moderately healthy group of Veterans with a history of mTBI 

(n=29,168).7 Compared to the phenotype of relatively healthy Veterans, both the Polytrauma and 

Moderately Healthy + Decline groups had significantly higher odds of SRB (adjusted OR=1.4 

and 1.3 respectively; CI not reported quantitatively).7 This study also compared the prevalence of 

suicide-related behaviors between those with and without a history of mTBI (eg, 6.6% versus 

2.4%, respectively) but did not likewise directly compare suicide-related behaviors between 

those with mTBI with and without comorbid pain. This study of the entire population of Post9/11 VA users defined pain based on ICD diagnosis codes. 

39%

48%

53%

45%

40%

50%

23%

0% 20% 40% 60% 80% 100%

Kulas, 2018

Suri, 2019

Suri, 2017

Wilk, 2010

Hoge, 2008

Wilk, 2012

MacGregor, 2013

Prevalence

Study

EHR CTBIE PHQ-15 PDHRA
Chronic Pain and mTBI Evidence Synthesis Program

64

KEY QUESTION 3. What are the benefits and harms of interventions to 

treat chronic pain in Veterans or Servicemembers with a history of 

mTBI?

Summary of Findings

Three studies12-14 met inclusion criteria and addressed KQ3. All 3 studies were focused on 

treatment for chronic headaches following mTBI. The studies by Leung et al (2016 and 2018) 

investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) in 2 small RCTs 

(N=29 and 44).12,13 Nelson and Esty (2015) conducted a small (N=9) pre-post study to 

investigate a “brainwave-based intervention” described as “the Flexyx Neurotherapy System 

(FNS) that involves minute pulses of electromagnetic energy stimulation of brainwave 

activity.”14 Table 7 describes study characteristics of the 3 included studies, including 

descriptions of the study samples and interventions; Table 8 provides additional study details 

including descriptions of the pain assessment tools used in these trials and outcomes. All 3 

studies examined intervention effects in adult US Veterans, many of whom experienced other 

comorbidities common among Veterans with mTBI history (eg, PTSD, depression, and cognitive 

dysfunction). Because of the high RoB ratings and small sample sizes of the included studies, the 

overall body of evidence was rated as having “insufficient” strength of evidence according to 

AHRQ EPC methods.

Of note is that no studies were identified that compared the efficacy of chronic pain treatments 

among those with, versus without, mTBI.

Detailed Results

Results from the 3 included studies are summarized in Table 8. Briefly, the 2 Leung et al studies 

(2016 and 2018)12,13 reported significantly greater reduction in persistent headaches in the rTMS 

group compared to the group randomized to the sham treatment condition. Similar results were 

obtained for debilitating headache exacerbation, with significantly greater reductions observed in 

the rTMS group compared to the sham group in both studies. Nonsignificant differences in 

global pain intensity were reported for both rTMS studies. Nelson and Esty (2015) reported a 

consistent decrease in mean pain scores over time, with a mean BPI-HA score of 7.3 (SD=1.2) 

decreasing to 2.9 (SD=2.6) after 20 FNS (neurotherapy) sessions for “worst pain past week” and 

a mean BPI-HA score of 4.6 (SD=1.6) decreasing to 1.4 (SD=1.2) after 20 sessions for “average 

pain past week.”14

Risk of Bias

Using the Cochrane Risk-of-Bias 2.0 criteria33 for RCTs and the Risk of Bias in Non-randomized 

Studies – of Interventions (ROBINS-I)34 for non-randomized intervention studies, we conducted 

a formal rating of the risk of bias (RoB) of the 3 included treatment studies (see Appendix C, 

Table 10 for full criteria). The Leung RCTs12,13 reported similar methods, though the study 

published earlier (2016) did not report adequate information on randomization, whereas the 2018 

publication reported adequate randomization methods. Neither study reported adequate detail on 

attrition after consent, and the 2018 study reported that only 29 out of 44 consented participants 

completed the study and were included in analyses. A notable strength, however, was the 

reliance on a well-designed and implemented sham control condition in these 2 trials, as well as 
Chronic Pain and mTBI Evidence Synthesis Program

65

similar baseline characteristics of treatment and control groups. The study by Nelson and 

colleagues14 provides less robust evidence primarily due to its reliance on a pre-post 

(uncontrolled) study design and the very small (N=9) sample size. Studies failed to provide 

adequate detail to assess RoB in numerous domains (eg, randomization, masking, attrition, 

fidelity). Overall, these 3 studies were all rated as having high RoB. Risk of bias ratings by 

domain are shown in Table 9. 

According to AHRQ methods,37,38 we considered study limitations, directness, consistency, 

precision, reporting bias, dose-response association, and plausible confounding that would 

decrease the observed effect, strength of association, and applicability to classify the strength of 

evidence for KQ3 outcomes. While all 3 studies investigated the population of interest, high RoB 

in combination with the very small number of studies (two from the same research team) and 

small sample sizes of included studies resulted in a strength of evidence rating of “insufficient” 

according to AHRQ EPC methods. The “insufficient” rating was based on the following AHRQ 

criteria: unable to estimate an effect, or no confidence in the estimate of effect for this outcome. 

The body of evidence has unacceptable deficiencies, precluding reaching a conclusion. 

KQ3a. Do the benefits or harms differ by mTBI etiology, type of chronic pain, mental 

health comorbidities, intervention setting, and demographics?

Due to the small number of pain trials on limited populations, generalizations about whether 

benefits and harms differ by mTBI etiology, type of chronic pain, mental health comorbidities, 

intervention setting, and demographics were not possible. 

KQ3b. How is pain assessed in clinical trials for comorbid chronic pain and history of 

mTBI in Veterans and Servicemembers?

Table 8 lists measures used to assess pain in clinical trials. Two of the 3 studies examined 

persistent headaches and debilitating headaches based on headache diaries using numeric rating 

scales (NRS).

12,13 These unvalidated headache pain assessments were both based on composite 

scores of average presence, duration, and intensity. All 3 studies also examined changes on the 

standardized Brief Pain Inventory (BPI), a validated self-report measure of global pain.

Table 7. Characteristics of studies of interventions for headaches in participants with a 

history of mTBI

Study 

design 

Intervention 

Total N Selection criteria

mTBI definition

and participant

characteristics Intervention Comparator Demographics

Leung, 

201612

RCT

N=24 (but 5 

participants 

dropped out 

from the 

study prior to 

intervention 

and were not 

US Veterans; age 

18-80; history of 

mTBI; diagnosed 

ICDH-2 

posttraumatic 

headache; average 

chronic persistent 

daily (24/7) 

headache 

intensity>30 on 0–

Head trauma with: 

either no LOC, or 

LOC<30 min 

duration; GCS score 

≥13; symptoms 

and/or signs 

diagnostic of 

concussion.

N=12

Three 

neuronavigation

-guided rTMS 

study 

treatments with

intertreatment 

interval at least 

24 hours or no 

N=12

Sham rTMS

Reported by 

treatment 

group; rTMS:

Age: 41.2±14.0 

yrs.

Female: 2/12 

(8.3%).

Sham: Age: 

41.4±11.6 yrs.
Chronic Pain and mTBI Evidence Synthesis Program

66

Study 

design 

Intervention 

Total N Selection criteria

mTBI definition

and participant

characteristics Intervention Comparator Demographics

included in 

analyses).

100 M-VAS at 

screening; and 

average pain 

intensity>3/10 on 

NRS reported in the 

headache diary 

(between visits 1-2)

Also: No prior 

experience of TMS 

treatment; no 

history of daily 

persistent headache 

prior to the mTBI 

incidence. 

more than 72 

hours apart 

were 

administered to 

the patients 

within 1 week. 

Female: 1/12 

(16.7%).

Mental health 

comorbidities: 

PTSD, 

depression, 

cognitive 

dysfunction.

Leung, 

201813

RCT

N=29 (but 15 

participants 

dropped out 

from the 

study prior to 

intervention 

and were not 

included in 

analyses)

US Veterans; age 

18-65; history of 

mTBI; diagnosed 

ICDH-2 

posttraumatic 

headache; average 

chronic persistent 

daily (24/7) 

headache 

intensity>30 on 0–

100 M-VAS at 

screening; and 

average pain 

intensity>3/10 on 

NRS reported in the 

headache diary 

(between visits 1-2)

Also: No prior 

experience of TMS 

treatment; no 

history of daily 

persistent headache 

prior to the mTBI 

incidence.

Head trauma with: 

either no LOC, or 

LOC<30 min 

duration; GCS score 

≥13; symptoms 

and/or signs 

diagnostic of 

concussion.

Based on published 

criteria from the 

1993 American 

Congress of 

Rehabilitation 

Medicine, and 

recent DoD 

recommendation. 

N=14

rTMS: at the left 

prefrontal cortex 

delivered at 10 

Hz, 80% of 

resting motor 

threshold and 

2000 pulses per 

session.

4 sessions 

at>24 and<72 

hours apart

N=15

Sham rTMS

Age: 34.1±7.9 

yrs.

Female: 6/29 

(20.7%).

Mental health 

comorbidities: 

depression, 

PTSD, cognitive 

dysfunction.

Nelson, 

201514

Pre-post

N=9 

US Veterans with 

wartime 

deployments in 

Afghanistan and/or 

Iraq; experienced 

service-connected 

TBI; other criteria 

NR.

Majority experienced 

some LOC (range: a 

few seconds to a 

number of minutes);

1 reported having 

experienced only 1 

concussion, the 

others reported 

having experienced 

multiple (typically 

“many” or “too many 

to count”), including 

N=9

FNS: 

Brainwavebased 

biofeedback. 

Involves subtle, 

minute pulses of 

EM stimulation 

computeradjusted based 

on EEG 

feedback. Total 

No 

comparator

Age: 37.3±12.6 

yrs (range: 25-

64). Time from 

end of most 

recent 

deployment to 

1st treatment: 6-

103 months 

(median=46).

Taking ≥1 Rx: 

7/9 (range=1–7; 

median=2). 
Chronic Pain and mTBI Evidence Synthesis Program

67

Study 

design 

Intervention 

Total N Selection criteria

mTBI definition

and participant

characteristics Intervention Comparator Demographics

exposures to 

explosive blasts.

of 4 s of EM 

stimulation 

spaced over 4 

minutes.

2–3 

sessions/week 

until 20 

sessions were 

completed.

Mental health 

comorbidities: 

PTSD (majority 

of participants); 

depressive 

disorders (3 

participants).

Abbreviations: DoD=Department of Defense; EEG=Electroencephalogram; EM=electromagnetic energy; 

FNS=Flexyx Neurotherapy System; GCS=Glasgow Coma Scale; ICDH-2=International Classification of Headache 

Disorders 2nd Edition; LOC=Loss of consciousness; mTBI=mild traumatic brain injury; M-VAS=Mechanical Visual 

Analog Scale; NR=Not reported; NRS=Numerical rating scale; PTSD=posttraumatic stress disorder; 

RCT=randomized controlled trial; rTMS=Repetitive transcranial magnetic stimulation; Rx=prescription medication; 

TBI=traumatic brain injury; TMS=transcranial magnetic stimulation
Chronic Pain and mTBI Evidence Synthesis Program

68

Table 8. Findings of studies of interventions for headaches in participants with a history of mTBI

Study design

T vs C

N (T vs C) Headache definition

Findings Risk of 

Headache pain Harms Bias

Leung, 201612

RCT

rTMS vs sham

12 vs 12

Persistent headaches: Betweenvisit persistent headache severity 

averaged (sum of headache rating

score/number of days) from daily 

headache diary.

Debilitating headache 

exacerbation: composite score 

generated by multiplying average 

duration (hours/episode) of 

headache exacerbation by average 

frequency (episodes/day) and 

average intensity (NRS)

Global Pain Intensity: BPI 

assessed baseline level of overall 

pain (total score divided by a factor 

of 4), the degree of headache relief 

(%) from the medication, and 

overall degree of interference (total 

score divided by 7) of pain on daily 

functions.

Persistent headaches: ANOVA (Visit × 

Treatment): (p=0.06; F=3.93; df=1) of treatment by 

time interaction. rTMS group had significantly 

(p=0.041; F=4.73; df=1) higher percentage of 

persistent headache intensity reduction than the 

sham group at 1-week posttreatment. A significantly 

(p=0.035; chi-square=4.44, df=1) higher percentage 

of rTMS participants (58.3%) demonstrated at least 

50% headache reduction than the SHAM group 

participants (16.6%) at 1-week posttreatment.

Debilitating headache exacerbation: Debilitating 

headache exacerbation was significantly (p=0.017, 

F=6.61; df=1.22) reduced in the rTMS group at 4-

weeks posttreatment compared to the sham group.

Global Pain Intensity: Visit and treatment 

interaction for global pain intensity was 

nonsignificant.

One participant had 

mild scalp discomfort, 

no other AEs reported. 

High

Leung, 201813

RCT

rTMS vs sham

14 vs 15

Persistent headaches: Betweenvisit persistent headache 

severity=averaged (sum of 

headache NRS score/number of 

days) from daily headache diary.

Debilitating headache 

exacerbation: Composite score 

generated by multiplying average 

duration (hours/episode) of 

headache exacerbation by average 

frequency (episodes/day) and 

average intensity (NRS)

Persistent Headaches: Two-factor (visit x 

treatment) ANOVA indicated an overall interaction 

for average daily persistent headache intensity 

(F=11.63, DF=1, p=0.002).Significant difference 

between groups at 1-week (F=21.75, p<0.0001) and 

4-weeks (F=11.56, p=0.002) posttreatment. At 4-

weeks posttreatment, 57% of the rTMS group no 

longer experienced persistent headaches compared 

to 20% of the sham group (F=6.76, p=0.009).

Debilitating Headache: Non-significant difference 

for debilitating headache composite scores (F=3.71, 

p=0.062). rTMS group decreased 55.1% (SD=29%) 

No AEs reported: 

“Aside from a transient 

elevation of 

Perservations score 

without an

overall significant 

treatment 3 visit 

interaction or 

behavioral correlation

in the REAL group at 

post-treatment oneweek assessment, the

High
Chronic Pain and mTBI Evidence Synthesis Program

69

Study design

T vs C

N (T vs C) Headache definition

Findings Risk of 

Headache pain Harms Bias

Global Pain Intensity: BPI 

assessed baseline level of overall 

pain (total score divided by a factor 

of 4), the degree of headache relief 

(%) from the medication, and 

overall degree of interference (total 

score divided by 7) of pain on daily 

functions.

at 1 week and 58.4% (SD=24.5%) at 4 weeks posttreatment whereas sham group decreased 1.7% 

(SD=41.2%) and 9.5% (SD=60.0%) at 1 week and 4

weeks post-treatment. Debilitating headache

duration (F=4.5, p=0.044) and debilitating HA 

frequency (F=5.57, p=0.026) had improvements in 

the rTMS vs sham groups. Global Pain Intensity: 

No significant interaction between visit and 

treatment on BPI pain interference.

study cohort reported 

no other side effects.”

Nelson, 201514

Pre-post

FNS 

N=9 

BPI was modified to indicate 0–10 

numeric ratings for pain intensity of 

headaches in the past week (0=no 

pain, 10=pain as bad as you can 

imagine), including worst 

headache pain and average 

headache pain. BPI completed at 

the beginning of treatment and then 

at sessions 5, 10, 15, and 20 (end 

of treatment)

Worst pain in past week: t(8)=5.43, p=0.001 

(results reported for baseline to end of treatment; 

means and SDs reported in study for multiple 

timepoints)

Average pain in past week: t(8)=5.86, p<0.001 

(results reported for baseline to end of treatment; 

means and SDs reported in study for multiple 

timepoints)

“...a few (rarely) 

reported minor 

intensifications of

their typical symptoms 

following a treatment 

session,

which was then 

followed by a more 

marked reduction in 

symptom intensity.”

High

Abbreviations: AE=Adverse event; ANOVA=Analysis of variance; BPI=Brief Pain Inventory; C=Comparator; df=degrees of freedom; NRS=Numeric Rating 

Scale; p=p-value; rTMS=Repetitive transcranial magnetic stimulation; SD=Standard deviation; T=Treatment
Chronic Pain and mTBI Evidence Synthesis Program

70

Table 9. Risk of bias in trials of interventions for chronic pain in Veterans with a history of mTBI

Study 

Intervention

vs 

comparator 

Randomization 

process 

Deviations 

from 

intended 

interventions

Missing 

outcome 

data 

Measurement 

of the

outcome 

Selection of 

the reported 

result 

Overall 

Bias Comment

Leung, 

201612 rTMS vs Sham rTMS

High Some 

concerns

High Some 

concerns

Low High Little information about 

randomization. Masking 

of providers and 

assessors was unclear. 

Analyzed completers only

and high attrition. 

Statistically 

underpowered.

Leung, 

201813

rTMS vs 

Sham rTMS

Low Some 

concerns

High Some 

concerns

Low High Masking of providers and 

assessors was unclear. 

Analyzed completers only

and high attrition. 

Statistically 

underpowered.

Abbreviations: rTMS=Repetitive transcranial magnetic stimulation
Chronic Pain and mTBI Evidence Synthesis Program

71

DISCUSSION

We identified 27 studies reporting chronic pain prevalence estimates in Veterans and SMs with a 

history of mTBI, 1 study that reported on prevalence of suicide-related behaviors among 

Veterans diagnosed with mTBI and chronic pain versus those with mTBI but no chronic pain 

diagnoses (and those with no mTBI), and 3 studies examining interventions for the treatment of 

chronic pain in Veterans and SMs with a history of mTBI. Included prevalence studies describe a 

wide range of chronic pain types, with the most common being head pain (23 studies), followed 

by back pain (10 studies), and arm, leg, and/or joint pain (9 studies). Four studies reported data 

on the use of pain medications (eg, analgesics including opioids, non-opioid analgesics) among 

Veterans and SMs with mTBI, which we abstracted as a proxy measure for chronic pain (see

Figure 8). Across studies addressing KQ1 and KQ2, there was significant heterogeneity in 

sample sizes (ie, 40 to 102,055 Veterans or SMs with history of mTBI), target populations (eg, 

Veterans, SMs, or both; era of service; combat exposure history; geographic region; comorbid 

physical or mental health conditions; and healthcare use), time since mTBI, and length of followup, as well as the methods used to identify, define, and operationalize both mTBI and chronic 

pain. In the studies addressing KQ3, all 3 interventions targeted the treatment of chronic 

headaches following mTBI – none examined other pain locations or compared efficacy of 

chronic pain treatments between those with and without mTBI history. 

Figure 8. Number of studies reporting prevalence of chronic pain in Veterans and 

Servicemembers with mTBI by pain type

Note. Some studies reported multiple pain types.
Chronic Pain and mTBI Evidence Synthesis Program

72

Across these studies, the prevalence of chronic pain among Veterans and SMs varied widely but, 

overall, was high. In studies providing comparisons, pain prevalence estimates were consistently 

higher among those with, versus without, mTBI history, and for those with comorbid mTBI and 

PTSD compared to those with mTBI but no PTSD. While more recent literature distinguishes 

between chronic pain and “high impact chronic pain,”62 the studies meeting our inclusion criteria 

were generally published prior to when this distinction was more commonly used, and therefore 

type and impact of chronic pain were often unclear. As expected in this population, prevalence 

estimates of head pain and those of chronic pain generally were higher than estimates of other 

specific chronic pain conditions (eg, chest pain, abdominal/stomach pain). However, across 

studies, there were wide ranges of prevalence estimates for each pain type, likely due to the 

varying study designs, target populations or samples, pain definitions, operationalization of key 

variables, and pain ascertainment periods (see Figure 9). This heterogeneity across studies limits 

the conclusions that can be drawn about the frequency of pain or the most common pain types 

among Veterans and SMs who experience mTBI.
Chronic Pain and mTBI Evidence Synthesis Program

73

Figure 9. Range of chronic pain prevalence estimates by pain type across studies
Chronic Pain and mTBI Evidence Synthesis Program

74

For general chronic pain among Veterans with a history of mTBI, a relatively robust prevalence 

estimate of 59% was identified in a large study of Post-9/11 Veterans who use VA healthcare 

and completed the Comprehensive TBI Evaluation (CTBIE).

4 This estimate was derived from a 

population-level database and, thus, represents a relatively large target population. However, 

Veterans who complete the CTBIE are generally seeking treatment for a variety of postdeployment health symptoms that may or may not be related to mTBI, or pain. The CTBIE is a 

standardized and templated clinical assessment completed by a specialty provider and includes 

standardized assessments of pain; however, patients who complete the CTBIE may not need 

pain-related care (ie, are not bothered by pain). When CTBIE data or pain diagnosis codes are 

used to estimate chronic pain, as in the case of this study, the true prevalence of chronic pain 

may be over- or underestimated.3,5 Most other studies examining general chronic pain included 

fewer than 500 participants, and varied in their methods used to identify and define chronic pain. 

The only other large study utilized EHR data and reported prevalence estimates of 82% for 

Veterans with a history of mTBI and comorbid PTSD, and 71% with no PTSD.39 This study 

identified chronic pain by the presence of a single pain-related ICD diagnosis code, and may

over- (or under-) estimate pain prevalence due to this approach.

3,5 Studies of pain 

disability/interference (defined as moderate-to-severe interference in daily functioning) due to 

chronic pain provided relatively consistent estimates of 70-75%.4,44 Studies of pain severity, 

based on self-report using Likert-like scales, indicated that roughly half of Veterans and SMs 

with a history of mTBI reported moderate to extreme/very severe pain,41,53 and studies that 

examined pain frequency reported that about one-third to one-half of SMs and Veterans with a 

history of mTBI experience pain more than 15 days per month.42,46,50,54

Head pain such as headaches and migraines were the most-studied chronic pain type among 

Veterans and SMs with mTBI history; prevalence estimates varied widely from 3% to 98%. 

Relatively robust, but still widely varied, estimates were derived from 5 large studies, all of 

which used her or CTBIE data and thus, for the reasons indicated above, may not represent the 

true prevalence of head pain across the population of Veterans or SMs with mTBI 

history.

7,39,45,52,53 Prevalence estimates of headache or migraines from 4 studies of Post-9/11 

Veterans with a history of mTBI ranged from 20% to 94% (this latter study reported data from a 

CTBIE item assessing the presence of any headaches), and 1 study of SMs reported a prevalence 

of 15%. Prevalence estimates appear to vary substantially by target population (eg, Veteran 

versus Servicemember; healthcare utilization), time since mTBI, length of follow-up, method for 

identifying and classifying chronic pain (and possibly mTBI), and data source. 

Prevalence estimates for back pain were largely consistent, falling between 32% and 44% for 

SMs in 3 studies using the PHQ-15,15,59,60 and 13%-15% for upper back pain, and 53%-58% for 

lower back pain among Veterans who completed the CTBIE.52,53 The 3 studies that used the 

PHQ-1515,59,60 also used similar methods overall, including a focus on very similar SM 

populations. We were unable to determine whether there was overlap between individual 

participants in these studies – a possibility given the database utilized. Therefore, we retained all

3 studies and report findings for all pain measures presented (which were remarkably consistent 

across studies). 

There was wide variation in the prevalence estimate of neck pain in Veterans with a history of 

mTBI. The 2 largest studies reported prevalence estimates of 6% (VA EHR data) and 23% 
Chronic Pain and mTBI Evidence Synthesis Program

75

(CTBIE).7,40 With the exception of arthritis (41% to 44%),40,57 the prevalence levels of other pain 

types were relatively low. 

Four articles reported data on pain medication use, which we abstracted as a proxy measure for 

chronic pain. Of these, 2 relatively small studies40,42 specifically looked at opioid use. Estimates 

were disparate at 12% and 49% of Veterans with a history of mTBI, but these studies differed 

substantially in data source, population, and timing of follow-up. None of these studies measured 

the chronicity of opioid or other pain medication use; as such, it was unclear if these medications 

were used for chronic pain or for more intermittent pain. Future studies that examine the 

prescription of pain medications to Veterans and SMs with mTBI should specify the duration of 

medication use. 

Three studies compared the prevalence of chronic pain in Veterans and SMs with a history of 

mTBI by etiology of the mTBI (all 3 compared blast versus non-blast etiologies). None of these 

studies provided compelling evidence that prevalence differed by etiology. However, 1 study 

presented data on headache prevalence among Veterans who experienced LOC after their mTBI,

versus those who only experienced AOC, and by blast versus non-blast etiology. This study

reported a statistically significant difference in headache prevalence among those whose mTBI 

resulted in LOC and was associated with blasts versus those whose mTBI resulted in LOC but 

was not associated with blasts (40% versus 23%, respectively).

60 There were no differences by 

blast/non-blast etiologies among those whose mTBI resulted only in AOC. None of the other 

pain types assessed in this study differed by mTBI etiology. Notably, none of the studies 

examined or compared pain prevalence by location of mTBI, location of co-occurring injuries, or 

timing of pain onset relative to the mTBI, which may all have important implications for onset 

and chronicity of pain conditions.

Although we did not find strong evidence suggesting that pain prevalence varied by mTBI 

etiology, it was clear across studies that, when examined, pain prevalence levels were 

substantially higher among those with comorbid PTSD. Although the assessment of pain 

prevalence by comorbid PTSD was not a specified focus of KQ1, the consistency of this finding 

across studies is noteworthy, particularly given the high prevalence of diagnosed PTSD among 

those with a history of mTBI. This finding lends further evidence to prior discourse about the 

“polytrauma clinical triad”25 and has implications for the ongoing clinical management of 

Veterans and SMs with mTBI. Notably, we did not find parallel comparisons in pain prevalence 

by other mental health comorbidities. This is an evident gap in the literature as other mental and 

behavioral health conditions are also highly prevalent among those with mTBI (eg, depression, 

substance use disorders) and it is likely that pain conditions may also vary by the presence of 

these comorbidities. Such data may also have clinical implications for treatment of pain 

conditions among those with mTBI history. Importantly, Veterans with mTBI have considerably 

higher VA healthcare utilization and care costs than those without mTBI history, a large 

proportion of which is associated with pain and mental health care utilization.63,64 Research that 

helps forecast ongoing healthcare needs and that, ultimately, can lead to improved functioning 

and quality of life outcomes for this complex patient population is critical.

In contrast to large differences between those with and without comorbid PTSD, the studies that 

reported pain prevalence by “severity” of mTBI (ie, mTBI events associated with LOC versus 

those only associated with AOC) reported only small differences, with slightly higher pain 
Chronic Pain and mTBI Evidence Synthesis Program

76

prevalence among those who experienced more severe mTBI.15,44,46,49,59,60 However, slightly 

larger differences in prevalence by mTBI severity were observed in the studies examining head 

pain.15,59,60

As evident, there was relatively little consistency in the design or outcomes of the studies used to 

address KQ1 and KQ2. Although the wide variation in estimates is not surprising given the 

heterogeneity in methods across studies, these findings, or rather the lack of concrete findings,

highlight a need to establish and implement consistent methods to assess pain conditions that are 

prevalent in US Veteran and SM populations. Studies are needed to assess the prevalence of 

chronic pain among all US Veterans and SMs with a history of mTBI (rather than, for example, 

treatment-seeking Veterans specifically) and to compare the prevalence levels of pain types by 

important Veteran and SM characteristics, including service history, physical and mental health 

comorbidities, and healthcare utilization patterns. Additionally, despite being beyond the scope 

of this review, we noted that few studies compared pain prevalence between those with and 

without mTBI and, thus, it remains unclear how pain conditions are associated with mTBI (ie, 

whether they tend to be more commonly diagnosed among treatment-seeking samples, whether 

they are a result of the mTBI itself, or whether they are a result of the same characteristics and 

exposures that led to mTBI). To answer these questions and to maximize usefulness of the 

evidence, studies that randomly sample Veterans and SMs, follow them over time, and use 

established and consistent definitions and operationalizations of mTBI and pain are needed.

Similarly, although we found well-conducted studies of treatment-seeking samples of Veterans 

and SMs that reported on chronic pain among those with mTBI, these studies by nature relied on 

selective (ie, non-random) samples and/or proxy measures of mTBI and pain such as ICD 

diagnosis codes. In some studies, ICD diagnoses were used to identify potential pain conditions 

even if the specific diagnoses are not associated with pain in all cases. For example, 

osteoarthritis diagnoses are used as a proxy for chronic pain in some studies, but recent research 

suggests that individuals diagnosed with osteoarthritis are not necessarily experiencing chronic 

pain.65 To better understand the prevalence of chronic pain conditions and, in particular, to 

anticipate treatment needs among Veterans and SMs who utilize the VA or Military Health 

System, random or otherwise representative samples of individuals with (and, for comparison, 

without) mTBI should be assessed using established and consistent chronic pain definitions and 

measures.

It is notable that a large number of studies focusing on chronic pain among Veterans with a 

history of mTBI were excluded from this review because they did not report prevalence levels 

but, rather, outcomes of pain measures on a continuous scale (ie, means and medians). This 

precluded our ability to synthesize these studies in the current review, but it stands to reason that 

additional information on pain severity, frequency, and interference, as well as differences in 

these measures by pain etiology or assessment methods, may be gleaned from this body of 

literature. Our review used a relatively flexible definition of “chronic pain” so as not to exclude 

potentially useful data. Although this approach increased the variance across studies in terms of 

pain outcomes, we felt this was an acceptable trade-off in attempt to include as many published 

studies as possible. As described above, our review did not examine the potential impacts of 

comorbid mental health conditions on prevalence estimates or outcomes of chronic pain, and this 

limitation could be addressed in future systematic reviews of this body of literature.
Chronic Pain and mTBI Evidence Synthesis Program

77

A secondary purpose of this review was to describe strategies researchers use to assess chronic 

pain as part of clinical trials. While all 3 intervention studies used the BPI – a common and wellvalidated measure of pain intensity and function – the small number of studies examining 

interventions for chronic pain in this population precludes most generalizations about measures 

used to assess pain. Future trials should rely on validated, commonly used measures to facilitate 

comparisons across studies. The Initiative on Methods, Measurement, and Pain Assessment in 

Clinical Trials (IMMPACT) has developed recommended measures and outcomes that should be 

assessed in chronic pain clinical trials, including the domains of pain intensity, physical 

functioning, emotional functioning, improvement and satisfaction with treatment, adverse events, 

and treatment adherence.66,67 These recommendations were promoted by a recent VA workgroup 

on developing core outcome measures in chronic pain research, which also recommended 

including changes in sleep as a study outcome.

68 Future chronic pain research in Veterans and 

SMs with mTBI history would benefit from the continued use of these strategies for assessing 

pain and its associated consequences.

Results for KQ1c examining pain assessment methods suggest that different types of pain 

assessment methods were associated with higher or lower pain prevalence estimates. In addition 

to pain assessment methods, other aspects of study design likely influenced prevalence estimates. 

For example, studies of specialized clinics designed to treat a particular condition would be 

expected to have higher rates of that condition (such as in the study by Ruff et al,

6 of a small 

sample seen in a polytrauma clinic) than studies examining the prevalence in a broad, full, or 

“all-comers” population (such as in studies examining all post-deployment SMs or identifying 

pain diagnoses in the EHR). 

For this review, we included studies of chronic pain even if the study did not include a rigorous 

assessment to determine the chronicity or severity of symptoms. For example, we included 

studies where pain symptoms were assessed only for the past month. While this methodology 

could result in over-estimation of the prevalence of chronic pain, we opted to include these 

studies in order to generate a fuller picture of the problem of pain among patients with a history 

of mTBI. Future research that aims to understand chronic pain in a sample of all Veterans/SMs

with mTBI history, or of specified treatment-seeking Veterans/SMs with mTBI history, would 

benefit from the assessment of pain chronicity (at least 3-6 months) and severity (moderate or 

higher). There are also recommended strategies for assessing chronic pain using administrative 

data, such as ICD diagnosis codes, that can improve the accuracy and comparability of 

prevalence estimates in these types of studies of chronic pain.

3

We found only a single study examining suicide-related outcomes in US Veterans and SMs with 

both chronic pain and a history of mTBI.7 This study used VA EHR data and categorized 

Veterans with and without a history of mTBI into trajectory groups based on an algorithm using 

ICD diagnosis codes. As compared to those with relatively low rates of mental health, pain, and 

other sensory diagnoses during the trajectory development period, Veterans with high mental 

health, post-concussive symptoms, and pain comorbidities were significantly more likely to have 

been diagnosed with suicidal ideation or attempt during the follow-up period. This study 

compared the prevalence of suicide-related behaviors between those with and without a history 

of mTBI (eg, 6.6% versus 2.4%, respectively) but did not likewise directly compare suiciderelated behaviors between those with mTBI with and without comorbid pain. However, 

considering the persistently higher rates of suicide in Veteran populations, and evidence 
Chronic Pain and mTBI Evidence Synthesis Program

78

suggesting increased risk among Veterans with mTBI,10,11,29,30 more research of this particularly 

vulnerable population is urgently needed.8,9

Although chronic pain is well established as a common comorbidity among Veterans and SMs 

with a history of mTBI, we found very few trials of interventions to treat chronic pain in this 

population, even when searching for studies from any country. The 3 studies that met inclusion 

criteria were small and provide insufficient strength evidence supporting the interventions 

studied (rTMS in 2 RCTs and FNS, a type of neurotherapy, in 1 small pre-post trial).12-14 All 3 

studies targeted chronic headaches, and none assessed nor treated other types of chronic pain.

Also of note is that no studies compared the efficacy of chronic pain treatments among those 

with, versus without, mTBI. This review was limited to chronic pain treatment trials of Veterans 

and SMs from any country with a history of mTBI because of the unique military-related 

circumstances (eg, blast exposure) that can contribute to pain in this population. However, due to 

the very small number of trials specific to this population, future efforts should consider results 

from pain interventions among broader populations (eg, adult civilians) or Veterans and SMs 

without a history of mTBI when making treatment, policy, or research scoping decisions. Future 

research could compare responses to chronic pain interventions for participants with and without 

mTBI history to determine mTBI results in a greater or lesser likelihood of benefit. Without such 

information, screening for presence and intensity of pain are likely warranted for Veterans and 

SMs with a history of mTBI so that they can be offered evidence-based treatment for chronic 

pain if needed.

Due to the prevalence of mTBI, and the prevalence and debilitating nature of chronic pain, in the

population of Veterans and SMs, it is clear that more research targeting the treatment of chronic 

pain amongst those with mTBI history is warranted. Specifically, studies of interventions 

established to be effective for treating chronic pain in other patient populations, particularly 

Veterans and SMs without mTBI, should be prioritized for testing in those with mTBI history. 

Additionally, because rTMS has been studied in 2 small, pilot RCTs with a strong sham 

comparator and has shown positive preliminary findings,12,13 additional, larger RCTs of rTMS 

for chronic pain in Veterans and SMs with mTBI history are likely warranted.

CONCLUSION

Chronic pain, particularly head and back pain, is common among US Veterans and 

Servicemembers with a history of mTBI, as is the use of pain-related medications, including 

opioids. Although pain is prevalent among Veterans and SMs in general, the results of this 

review suggest that those with mTBI history – and especially those with comorbid mTBI and 

PTSD – experience pain at higher prevalence levels than those without a history of mTBI. Based 

on the existing research, precise estimates of the prevalence of pain conditions, locations, 

disability/interference, and severity are hampered by heterogeneity in study populations/samples, 

timing of pain ascertainment relative to individuals’ mTBI history, duration of study follow-up, 

and methods used to identify, define, and operationalize both mTBI and chronic pain. 

Additionally, only a single study examined the risk of suicide, and only 3 studies tested

interventions to mitigate pain in this complex population. Thus, the prevalence of chronic pain in 

the general population of US Veterans and SMs, the impact of comorbid pain and mTBI on 

suicide risk in this potentially high-risk population, and the efficacy of pain therapies among 

those with comorbid mTBI and chronic pain remain largely unknown. Research studies, 
Chronic Pain and mTBI Evidence Synthesis Program

79

specifically designed with the intent of filling these knowledge gaps, are needed to inform 

current and future service needs for this population. Given the high prevalence of mTBI in 

Veterans and Servicemembers, and the importance of meeting the social and clinical needs of 

this large population, this research is urgent and essential.
Chronic Pain and mTBI Evidence Synthesis Program

80

REFERENCES

1. Treede RD, Rief W, Barke A, et al. Chronic pain as a symptom or a disease: the IASP 

Classification of Chronic Pain for the International Classification of Diseases (ICD-11). 

Pain. 2019;160(1):19-27.

2. Department of Veterans Affairs/Department of Defense. VA/DoD Clinical Practice 

Guideline for the Management of Concussion-Mild Traumatic Brain Injury. Washington, 

DC2016.

3. Abel EA, Brandt CA, Czlapinski R, Goulet JL. Pain research using Veterans Health 

Administration electronic and administrative data sources. J Rehabil Res Dev. 

2016;53(1):1-12.

4. Seal KH, Bertenthal D, Barnes DE, et al. Association of Traumatic Brain Injury With 

Chronic Pain in Iraq and Afghanistan Veterans: Effect of Comorbid Mental Health 

Conditions. Arch Phys Med Rehabil. 2017;98(8):1636-1645.

5. Carlson KF, Barnes JE, Hagel EM, Taylor BC, Cifu DX, Sayer NA. Sensitivity and 

specificity of traumatic brain injury diagnosis codes in United States Department of 

Veterans Affairs administrative data. Brain Inj. 2013;27(6):640-650.

6. Ruff RL, Ruff SS, Wang XF. Headaches among Operation Iraqi Freedom/Operation 

Enduring Freedom veterans with mild traumatic brain injury associated with exposures to 

explosions. J Rehabil Res Dev. 2008;45(7):941-952.

7. Pugh MJ, Swan AA, Amuan ME, et al. Deployment, suicide, and overdose among 

comorbidity phenotypes following mild traumatic brain injury: A retrospective cohort 

study from the Chronic Effects of Neurotrauma Consortium. PLoS ONE. 

2019;14(9):e0222674.

8. VHA Office of Mental Health and Suicide Prevention. VA National Suicide Data Report 

2005–2016. September 2018.

9. VHA Office of Mental Health and Suicide Prevention. National Strategy for Preventing 

Veteran Suicide 2018-2028. 2018.

10. Byers AL, Li Y, Barnes DE, Seal KH, Boscardin WJ, Yaffe K. A national study of TBI 

and risk of suicide and unintended death by overdose and firearms. Brain Inj. 

2020;34(3):328-334.

11. Madsen T, Erlangsen A, Orlovska S, Mofaddy R, Nordentoft M, Benros ME. Association 

Between Traumatic Brain Injury and Risk of Suicide. Jama. 2018;320(6):580-588.

12. Leung A, Shukla S, Fallah A, et al. Repetitive Transcranial Magnetic Stimulation in 

Managing Mild Traumatic Brain Injury-Related Headaches. Neuromodulation. 

2016;19(2):133-141.

13. Leung A, Metzger-Smith V, He Y, et al. Left Dorsolateral Prefrontal Cortex rTMS in 

Alleviating MTBI Related Headaches and Depressive Symptoms. Neuromodulation. 

2018;21(4):390-401.

14. Nelson DV, Esty ML. Neurotherapy for chronic headache following traumatic brain 

injury. Mil. 2015;2:22.

15. Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain 

injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008;358(5):453-463.

16. Defense and Veterans Brain Injury Center. DoD Worldwide Numbers for TBI. (2000-

2019 Q3) Web site. https://dvbic.dcoe.mil/dod-worldwide-numbers-tbi. Published 2019. 

Accessed January 28, 2020.
Chronic Pain and mTBI Evidence Synthesis Program

81

17. Carroll LJ, Cassidy JD, Cancelliere C, et al. Systematic review of the prognosis after mild 

traumatic brain injury in adults: cognitive, psychiatric, and mortality outcomes: results of 

the International Collaboration on Mild Traumatic Brain Injury Prognosis. Arch Phys 

Med Rehabil. 2014;95(3 Suppl):S152-173.

18. O'Neil ME, Carlson KF, Storzbach D, et al. Factors Associated with Mild Traumatic 

Brain Injury in Veterans and Military Personnel: A Systematic Review. J Int 

Neuropsychol Soc. 2014:1-13.

19. Ruff R. Two decades of advances in understanding of mild traumatic brain injury. J Head 

Trauma Rehabil. 2005;20(1):5-18.

20. Department of Veterans Affairs. Polytrauma System of Care. In: Veterans Health 

Administration, ed. Vol VHA Directive 1172.01. Washington, DC2019.

21. Hendricks AM, Amara J, Baker E, et al. Screening for mild traumatic brain injury in 

OEF-OIF deployed US military: an empirical assessment of VHA's experience. Brain Inj. 

2013;27(2):125-134.

22. Vanderploeg RD, Belanger HG. Screening for a remote history of mild traumatic brain 

injury: when a good idea is bad. J Head Trauma Rehabil. 2013;28(3):211-218.

23. Hoge CW, Goldberg HM, Castro CA. Care of war veterans with mild traumatic brain 

injury--flawed perspectives. N Engl J Med. 2009;360(16):1588-1591.

24. Vasterling JJ, Aslan M, Lee LO, et al. Longitudinal Associations among Posttraumatic 

Stress Disorder Symptoms, Traumatic Brain Injury, and Neurocognitive Functioning in 

Army Soldiers Deployed to the Iraq War. J Int Neuropsychol Soc. 2018;24(4):311-323.

25. Lew HL, Otis JD, Tun C, Kerns RD, Clark ME, Cifu DX. Prevalence of chronic pain, 

posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF 

veterans: polytrauma clinical triad. J Rehabil Res Dev. 2009;46(6):697-702.

26. Pagulayan KF, O'Neil M, Williams RM, et al. Mental Health Does Not Moderate 

Compensatory Cognitive Training Efficacy for Veterans With a History of Mild 

Traumatic Brain Injury. Arch Phys Med Rehabil. 2017;98(9):1893-1896.e1892.

27. Irvine KA, Clark JD. Chronic Pain After Traumatic Brain Injury: Pathophysiology and 

Pain Mechanisms. Pain Med. 2018;19(7):1315-1333.

28. Prevention VOoMHaS. 2019 National Veteran Suicide Prevention Annual Report. 2019.

29. Finley EP, Bollinger M, Noel PH, et al. A national cohort study of the association 

between the polytrauma clinical triad and suicide-related behavior among US Veterans 

who served in Iraq and Afghanistan. Am J Public Health. 2015;105(2):380-387.

30. Hostetter TA, Hoffmire CA, Forster JE, Adams RS, Stearns-Yoder KA, Brenner LA. 

Suicide and Traumatic Brain Injury Among Individuals Seeking Veterans Health 

Administration Services Between Fiscal Years 2006 and 2015. J Head Trauma Rehabil. 

2019;34(5):E1-e9.

31. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer 

Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 

2016;75:40-46.

32. Treadwell JR, Singh S, Talati R, McPheeters ML, Reston JT. A framework for best 

evidence approaches can improve the transparency of systematic reviews. J Clin 

Epidemiol. 2012;65(11):1159-1162.

33. Higgins J, Savovic J, Page MJ, Sterne JA. Revised Cochrane risk-of-bias tool for 

randomized trials (RoB 2). https://methods.cochrane.org/bias/resources/rob-2-revisedcochrane-risk-bias-tool-randomized-trials. 2019.
Chronic Pain and mTBI Evidence Synthesis Program

82

34. Sterne JA, Hernan MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in 

non-randomised studies of interventions. Bmj. 2016;355:i4919.

35. Wells G, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing 

the quality of nonrandomised studies in meta-analyses. 

http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 1/31/2020.

36. Munn Z, Moola S, Riitano D, Lisy K. The development of a critical appraisal tool for use 

in systematic reviews addressing questions of prevalence. International journal of health 

policy and management. 2014;3(3):123-128.

37. Berkman ND, Lohr KN, Ansari MT, et al. Grading the strength of a body of evidence 

when assessing health care interventions: an EPC update. J Clin Epidemiol. 

2015;68(11):1312-1324.

38. Atkins D, Chang SM, Gartlehner G, et al. Assessing applicability when comparing 

medical interventions: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 

2011;64(11):1198-1207.

39. Kulas JF, Rosenheck RA. A Comparison of Veterans with Post-traumatic Stress 

Disorder, with Mild Traumatic Brain Injury and with Both Disorders: Understanding 

Multimorbidity. Mil Med. 2018;183(3-4):e114-e122.

40. King PR, Wade MJ, Beehler GP. Health service and medication use among veterans with 

persistent postconcussive symptoms. J Nerv Ment Dis. 2014;202(3):231-238.

41. Hoot MR, Levin HS, Smith AN, et al. Pain and chronic mild traumatic brain injury in the 

US military population: a Chronic Effects of Neurotrauma Consortium study. Brain Inj. 

2018;32(10):1169-1177.

42. Brickell TA, Lange RT, French LM. Health-related quality of life within the first 5 years 

following military-related concurrent mild traumatic brain injury and polytrauma. Mil 

Med. 2014;179(8):827-838.

43. Powell MA, Corbo V, Fonda JR, Otis JD, Milberg WP, McGlinchey RE. Sleep Quality 

and Reexperiencing Symptoms of PTSD Are Associated With Current Pain in U.S. 

OEF/OIF/OND Veterans With and Without mTBIs. J Trauma Stress. 2015;28(4):322-

329.

44. Romesser J, Booth J, Benge J, Pastorek N, Helmer D. Mild traumatic brain injury and 

pain in Operation Iraqi Freedom/Operation Enduring Freedom veterans. J Rehabil Res 

Dev. 2012;49(7):1127-1136.

45. Beswick-Escanlar VP, Lee T, Hu Z, Clark LL. Increasing severity of traumatic brain 

injury is associated with an increased risk of subsequent headache or migraine: a 

retrospective cohort study of U.S. active duty service members, 2006-2015. Msmr. 

2016;23(7):2-8.

46. Couch JR, Stewart KE. Headache Prevalence at 4-11 Years After Deployment-Related 

Traumatic Brain Injury in Veterans of Iraq and Afghanistan Wars and Comparison to 

Controls: A Matched Case-Controlled Study. Headache. 2016;56(6):1004-1021.

47. Farrell-Carnahan L, Barnett S, Lamberty G, et al. Insomnia symptoms and behavioural 

health symptoms in veterans 1 year after traumatic brain injury. Brain Inj. 2015:1-9.

48. Jackson CE, Green JD, Bovin MJ, et al. Mild Traumatic Brain Injury, PTSD, and 

Psychosocial Functioning Among Male and Female U.S. OEF/OIF Veterans. J Trauma 

Stress. 2016;29(4):309-316.
Chronic Pain and mTBI Evidence Synthesis Program

83

49. MacGregor AJ, Dougherty AL, Tang JJ, Galarneau MR. Postconcussive symptom 

reporting among US combat veterans with mild traumatic brain injury from Operation 

Iraqi Freedom. J Head Trauma Rehabil. 2013;28(1):59-67.

50. Patil VK, St Andre JR, Crisan E, et al. Prevalence and treatment of headaches in veterans 

with mild traumatic brain injury. Headache. 2011;51(7):1112-1121.

51. Schwab K, Terrio HP, Brenner LA, et al. Epidemiology and prognosis of mild traumatic 

brain injury in returning soldiers: A cohort study. Neurology. 2017;88(16):1571-1579.

52. Suri P, Stolzmann K, Williams R, Pogoda TK. Deployment-Related Traumatic Brain 

Injury and Risk of New Episodes of Care for Back Pain in Veterans. J Pain. 

2019;20(1):97-107.

53. Suri P, Stolzmann K, Iverson KM, et al. Associations Between Traumatic Brain Injury 

History and Future Headache Severity in Veterans: A Longitudinal Study. Arch Phys 

Med Rehabil. 2017;98(11):2118-2125.e2111.

54. Theeler BJ, Flynn FG, Erickson JC. Chronic daily headache in U.S. soldiers after 

concussion. Headache. 2012;52(5):732-738.

55. Tsao JW, Stentz LA, Rouhanian M, et al. Effect of concussion and blast exposure on 

symptoms after military deployment. Neurology. 2017;89(19):2010-2016.

56. Vanderploeg RD, Belanger HG, Curtiss G. Mild traumatic brain injury and posttraumatic 

stress disorder and their associations with health symptoms. Arch Phys Med Rehabil. 

2009;90(7):1084-1093.

57. Walker WC, Hirsch S, Carne W, et al. Chronic Effects of Neurotrauma Consortium 

(CENC) multicentre study interim analysis: Differences between participants with 

positive versus negative mild TBI histories. Brain Inj. 2018;32(9):1079-1089.

58. Webb TS, Whitehead CR, Wells TS, Gore RK, Otte CN. Neurologically-related sequelae 

associated with mild traumatic brain injury. Brain Inj. 2015;29(4):430-437.

59. Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury 

(concussion), posttraumatic stress disorder, and depression in U.S. soldiers involved in 

combat deployments: association with postdeployment symptoms. Psychosom Med. 

2012;74(3):249-257.

60. Wilk JE, Thomas JL, McGurk DM, Riviere LA, Castro CA, Hoge CW. Mild traumatic 

brain injury (concussion) during combat: lack of association of blast mechanism with 

persistent postconcussive symptoms. J Head Trauma Rehabil. 2010;25(1):9-14.

61. Walker WC, Nowak KJ, Kenney K, et al. Is balance performance reduced after mild 

traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium 

(CENC) multi-centre study. Brain Inj. 2018;32(10):1156-1168.

62. NIH study broadens understanding of High Impact Chronic Pain in the U.S. [press 

release]. September 5 2018.

63. Dismuke-Greer C, Hirsch S, Carlson K, et al. Health Services Utilization, Health Care 

Costs, and Diagnoses by Mild Traumatic Brain Injury Exposure: A Chronic Effects of 

Neurotrauma Consortium Study. Archives of Physical Medicine and Rehabilitation. 2020.

64. Taylor BC, Hagel EM, Carlson KF, et al. Prevalence and costs of co-occurring traumatic 

brain injury with and without psychiatric disturbance and pain among Afghanistan and 

Iraq War Veteran V.A. users. Med Care. 2012;50(4):342-346.

65. Goulet JL, Kerns RD, Bair M, et al. The musculoskeletal diagnosis cohort: examining 

pain and pain care among veterans. Pain. 2016;157(8):1696-1703.
Chronic Pain and mTBI Evidence Synthesis Program

84

66. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical 

trials: IMMPACT recommendations. Pain. 2005;113(1).

67. Turk DC, Dworkin RH, Allen RR, et al. Core outcome domains for chronic pain clinical 

trials: IMMPACT recommendations. Pain. 2003;106(3):337-345.

68. Kroenke K, Krebs EE, Turk D, et al. Core Outcome Measures for Chronic 

Musculoskeletal Pain Research: Recommendations from a Veterans Health 

Administration Work Group. Pain Med. 2019;20(8):1500-1508.
Chronic Pain and mTBI Evidence Synthesis Program

85

APPENDIX A. SEARCH STRATEGIES

Ovid MEDLINE(R) ALL 1946 to March 04, 2020 

Date searched: March 5, 2020 

1 Brain Concussion/ or Brain Contusion/ or Brain Hemorrhage, Traumatic/ or Brain 

Injuries, Traumatic/ or Brain Stem Hemorrhage, Traumatic/ or Cerebral Hemorrhage, 

Traumatic/ or Chronic Traumatic Encephalopathy/ or Contrecoup Injury/ or 

Craniocerebral Trauma/ or Head Injuries, Closed/ or Intracranial Hemorrhage, 

Traumatic/ or Post-concussion Syndrome/ or Blast Injuries/

2 (TBI or mTBI or bTBI or ((trauma or traumas or traumatic or posttraumatic or posttraumatic) adj2 (brain or crania* or cranio* or cerebr* or cortex or cortical or head*)) or 

concussion or concussions or concussive or contrecoup or coup-contrecoup or "minor 

brain" or "minor head" or postconcussion or postconcussive or post-concussion or postconcussive).ti,ab,kf.

3 or/1-2

4 Arthritis/ or Arthritis, Psoriatic/ or exp Arthritis, Rheumatoid/ or Back Pain/ or Chronic 

Pain/ or exp Chondrocalcinosis/ or Complex Regional Pain Syndromes/ or exp Facial 

Neuralgia/ or Fatigue Syndrome, Chronic/ or Femoral Neuropathy/ or Fibromyalgia/ or 

exp Gout/ or Headache/ or Headache Disorders/ or Headache Disorders, Primary/ or 

Headache Disorders, Secondary/ or Low Back Pain/ or exp Migraine Disorders/ or 

Musculoskeletal Pain/ or Myalgia/ or Myofascial Pain Syndromes/ or Neck Pain/ or exp 

Neuralgia/ or exp Osteoarthritis/ or Pain, Intractable/ or Phantom Limb/ or PostTraumatic Headache/ or Radial Neuropathy/ or exp Spondylosis/ or Tension-type 

Headache/ or exp Trigeminal Autonomic Cephalalgias/ or Vascular Headaches/

5 (exp Pain/ or pain.hw.) and (arthrit* or "complex regional pain" or CRPS or 

fibromyalgia or gout or headache* or "low back" or migrain* or myalgia or neuralgia or 

neuropath* or nocicept* or osteoarthrit* or osteo-arthrit* or "phantom limb" or "reflex 

sympathetic dystrophy" or spondylosis or (central* adj2 (pain* or sensit*))).ti,ab,kf.

6 (arthrit* or "chronic fatigue" or "complex regional pain" or CRPS or fibromyalgia or 

gout or headache* or migrain* or myalgia or neuralgia or neuropath* or nocicept* or 

osteoarthrit* or osteo-arthrit* or "phantom limb" or “polytrauma clinical triad” or 

"reflex sympathetic dystrophy" or spondylosis or (central* adj2 (pain* or sensit*)) or 

pain).ti,ab,kf.

7 or/4-6

8 and/3,7

9 8 not ((exp Animals/ not Humans/) or ("animal model*" or cat or cats or dog or dogs or 

mice or mouse or rat or rats or rodent).ti.)

10 9 not (((Adolescent/ or exp Child/ or exp Infant/) not exp Adult/) or (adolescent or 

adolescents or adolescence or child or children or childhood or juvenile or pediatric or 

paediatric or preschool or pre-school or school-age or teen or teens or teenager or 

teenagers or youth or youths).ti.)

11 10 not case reports.pt.
Chronic Pain and mTBI Evidence Synthesis Program

86

12 limit 11 to english language 

Veteran/ Servicemember filter terms used:

13 exp Veterans/ or exp "United States Department of Veterans Affairs"/ or exp Veterans 

Disability Claims/ or exp Veterans Health/ or Veterans Health Services/ or exp 

Hospitals, Veterans/ or Aerospace Medicine/ or Armed Conflicts/ or Hospitals, 

Military/ or Military Health/ or Military Personnel/ or Military Medicine/ or Military 

Nursing/ or Military Psychiatry/ or exp Naval Medicine/ or Psychology, Military/ or 

Gulf War/ or Vietnam Conflict/ or World War ii/ or Afghan Campaign 2001-/ or Iraq 

War, 2003-2011/ or War/ or exp "Warfare and Armed Conflicts"/ or War-Related 

Injuries/ or War Exposure/ or Warfare/ or Biological Warfare/ or Chemical Warfare/ or 

Nuclear Warfare/ or Psychological Warfare/

14 ("active duty" or "armed forces" or "armed service*" or "coast guard*" or military or 

"air force" or army or "defense force*" or "marine corps" or marines or "national 

guard*" or (navy not bean) or naval or "security force*" or air-men or air-man or 

airmen or airman or corpsman or corpsmen or guardsman or guardsmen or infantry* or 

medic or medics or reservist* or sailor* or soldier* or servicemember* or servicemember* or "special forces" or submariner* or troops or battle* or combat or deployed 

or deployment* or post-deployment* or postdeployment* or veteran* or VAMC or 

Veterans Administration Medical Center* or VHA or Veterans* Health Administration 

or war or wars or warfare or war-fighter* or warfighter* or war-related).tw,kf.

15 (((VA or Veteran Affairs or Veterans' Affairs or Veterans Affairs or Veterans 

Administration) adj4 (health care system or healthcare system or medical center or 

hospital)) or VAMC or Veteran Affairs or Veterans' Affairs or Veterans Affairs or 

Veterans Administration Medical Center or Veterans' Affairs Medical Center or 

Veterans Affairs Medical Center or Veterans Health Administration or QUERI or 

"Mental Health Quality Enhancement Research Initiative" or HSR&D or "Center of 

Innovation for Veteran-Centered Value-Driven Care" or "Evidence-based Synthesis 

Program" or ((Veteran* or VA) adj5 (Office of Research and Development)) or "Center 

for Health Equity Research and Promotion" or "Women's Health Research Network" or 

"Cooperative Studies Program" or "Million Veteran Program").in.

16 (military or army or soldier* or navy* or veteran or veterans).jw.

17 or/13-16

18 and/12,17

CINAHL Plus with Full Text (EBSCOHost)

Date searched: February 10, 2020 

S1 MH Brain Concussion OR Brain Contusions OR Brain Injuries OR Chronic Traumatic 

Encephalopathy OR Head Injuries (32,064) 

S2 TI ( TBI OR mTBI OR bTBI OR ((trauma OR traumas OR traumatic OR posttraumatic OR 

post-traumatic) N2 (brain OR crania* OR cranio* OR cerebr* OR cortex OR cortical OR 

head*)) OR concussion OR concussions OR concussive OR contrecoup OR coup-contrecoup OR 

"minor brain" OR "minor head" OR postconcussion OR postconcussive OR post-concussion OR 

post-concussive ) OR AB ( TBI OR mTBI OR bTBI OR ((trauma OR traumas OR traumatic OR 
Chronic Pain and mTBI Evidence Synthesis Program

87

posttraumatic OR post-traumatic) N2 (brain OR crania* OR cranio* OR cerebr* OR cortex OR 

cortical OR head*)) OR concussion OR concussions OR concussive OR contrecoup OR coupcontrecoup OR "minor brain" OR "minor head" OR postconcussion OR postconcussive OR postconcussion OR post-concussive ) (22,788)

S3 S1 OR S2 (38,328) 

S4 MH Arthritis OR Arthritis, Psoriatic OR Arthritis, Rheumatoid OR Back Pain OR 

Chondrocalcinosis OR Chronic Pain OR Cluster Headache OR Complex Regional Pain 

Syndromes OR Facial Pain OR Fatigue Syndrome, Chronic OR Gout OR Headache OR 

Headache, Primary OR Headache, Secondary OR Low Back Pain OR Migraine OR Muscle Pain 

OR Myofascial Pain Syndromes OR Neck Pain OR Neuralgia OR Osteoarthritis OR Phantom 

Limb OR Phantom Pain OR Spondylosis OR Tension Headache OR Trigeminal Autonomic 

Cephalalgias OR Vascular Headache (127,543) 

S5 TI ( arthrit* OR chondrocalcinosis OR "chronic fatigue" OR "complex regional pain" OR 

CRPS OR fibromyalgia OR gout OR headache* OR "low back" OR migrain* OR 

musculoskeletal OR musculo-skeletal OR myalgia OR neuralgia OR neuropath* OR nocicept* 

OR osteoarthrit* OR osteo-arthrit* OR "phantom limb" OR "reflex sympathetic dystrophy" OR 

spondylosis OR (central* N2 (pain* OR sensit*)) OR ((chronic OR intractable OR long-term OR 

longer-term OR noncancer OR non-cancer OR nonmalignant OR non-malignant OR persistent* 

OR refractory) N3 pain) ) OR AB ( arthrit* OR chondrocalcinosis OR "chronic fatigue" OR 

"complex regional pain" OR CRPS OR fibromyalgia OR gout OR headache* OR "low back" OR 

migrain* OR musculoskeletal OR musculo-skeletal OR myalgia OR neuralgia OR neuropath* 

OR nocicept* OR osteoarthrit* OR osteo-arthrit* OR "phantom limb" OR "reflex sympathetic 

dystrophy" OR spondylosis OR (central* N2 (pain* OR sensit*)) OR ((chronic OR intractable 

OR long-term OR longer-term OR noncancer OR non-cancer OR nonmalignant OR nonmalignant OR persistent* OR refractory) N3 pain) ) (198,244)

S6 S4 OR S5 (239,755) 

S7 S3 AND S6 Limiters - English Language; Human; Age Groups: Adult: 19-44 years, Middle 

Aged: 45-64 years, Aged: 65+ years, Aged, 80 and over, All Adult (435) 

PsycINFO (Ovid) 1806 to February Week 1 2020 

Date searched: February 7, 2020 

1 Traumatic Brain Injury/ or Brain Concussion/ (19109) 

2 (TBI or mTBI or bTBI or ((trauma or traumas or traumatic or posttraumatic or post-traumatic) 

adj2 (brain or crania* or cranio* or cerebr* or cortex or cortical or head*)) or concussion or 

concussions or concussive or contrecoup or coup-contrecoup or "minor brain" or "minor head" or 

postconcussion or postconcussive or post-concussion or post-concussive).ti,ab. (21754)

3 or/1-2 (25224)

4 Arthritis/ or Rheumatoid Arthritis/ or Back Pain/ or Chronic Pain/ or "Complex Regional Pain 

Syndrome (Type I)"/ or Chronic Fatigue Syndrome/ or Fibromyalgia/ or Headache/ or Migraine 

Headache/ or Myofascial Pain/ or Muscle Contraction Headache/ or Neuropathy/ or Neuropathic 

Pain/ or Phantom Limbs/ or Trigeminal Neuralgia/ (43617) 

5 (arthrit* or chondrocalcinosis or "chronic fatigue" or "complex regional pain" or CRPS or 

fibromyalgia or gout or headache* or "low back" or migrain* or musculoskeletal or musculoskeletal or myalgia or neuralgia or neuropath* or nocicept* or osteoarthrit* or osteo-arthrit* or 

"phantom limb" or "reflex sympathetic dystrophy" or spondylosis or (central* adj2 (pain* or 
Chronic Pain and mTBI Evidence Synthesis Program

88

sensit*)) or ((chronic or intractable or long-term or longer-term or noncancer or non-cancer or 

nonmalignant or non-malignant or persist?nt* or refractory) adj3 pain)).ti,ab. (86759)

6 or/4-5 (89596)

7 and/3,6 (1680) 

8 limit 7 to animal (246)

9 7 not 8 (1434) 

10 limit 9 to ("300 adulthood<age 18 yrs and older>" or 320 young adulthood<age 18 to 29 

yrs>or 340 thirties<age 30 to 39 yrs>or 360 middle age<age 40 to 64 yrs>or "380 aged<age 65 

yrs and older>" or "390 very old<age 85 yrs and older>") (711) 

11 9 not (adolescent or adolescents or adolescence or child or children or childhood or juvenile 

or pediatric or paediatric or preschool or pre-school or school-age or teen or teens or teenager or 

teenagers or youth or youths).ti. (1327) 

12 or/10-11 (1355)

13 limit 12 to ("0200 clinical case study" or 1400 nonclinical case study) (127) 

14 12 not 13 (1228) 

15 limit 14 to english language (1180)

EBM Reviews (Ovid) - Cochrane Central Register of Controlled Trials (December 2019)

and Cochrane Database of Systematic Reviews (2005 to February 4, 2020) 

Date searched: February 7, 2020 

1 (TBI or mTBI or bTBI or ((trauma or traumas or traumatic or posttraumatic or post-traumatic) 

adj2 (brain or crania* or cranio* or cerebr* or cortex or cortical or head*)) or concussion or 

concussions or concussive or contrecoup or coup-contrecoup or "minor brain" or "minor head" or 

postconcussion or postconcussive or post-concussion or post-concussive).ti,ab. (5149)

2 (arthrit* or "chronic fatigue" or "complex regional pain" or CRPS or fibromyalgia or gout or 

headache* or "low back" or migrain* or myalgia or neuralgia or neuropath* or nocicept* or 

osteoarthrit* or osteo-arthrit* or "phantom limb" or "reflex sympathetic dystrophy" or 

spondylosis or (central* adj2 (pain* or sensit*)) or ((chronic or intractable or long-term or 

longer-term or noncancer or non-cancer or nonmalignant or non-malignant or persist?nt* or 

refractory) adj3 pain)).ti,ab. (87910) 

3 and/1-2 (297) 

4 3 not ("animal model*" or cat or cats or dog or dogs or mice or mouse or rat or rats or 

rodent).ti. (297)

5 4 not (adolescent or adolescents or adolescence or child or children or childhood or juvenile or 

pediatric or paediatric or preschool or pre-school or school-age or teen or teens or teenager or 

teenagers or youth or youths).ti. (273) 

Scopus

Date searched: February 10, 2020 

( TITLE-ABS-KEY ( tbi OR mtbi OR btbi OR ( ( trauma* OR posttraumatic OR post-traumatic )

W/2 ( brain OR crania* OR cranio* OR cerebr* OR cortex OR cortical OR head* ) ) OR

concussion* OR concussive OR contrecoup OR coup-contrecoup OR "minor brain" OR "minor 

head" OR postconcuss* ) ) AND ( ( TITLE-ABS-KEY ( arthrit* OR "chronic fatigue" OR

"complex regional pain" OR crps OR fibromyalgia OR gout OR headache* OR migrain* OR

myalgia OR neuralgia OR neuropath* OR nocicept* OR osteoarthrit* OR osteo-arthrit* OR

"phantom limb" ) OR TITLE-ABS-KEY ( "reflex sympathetic dystrophy" OR spondylosis OR ( 
Chronic Pain and mTBI Evidence Synthesis Program

89

central* W/2 ( pain* OR sensit* ) ) OR ( ( chronic OR intractable OR long-term OR longer-term

OR noncancer OR non-cancer OR nonmalignant OR non-malignant OR persist?nt* OR

refractory ) W/3 pain ) ) ) ) AND ( LIMIT-TO ( DOCTYPE , "cp" ) ) AND ( LIMIT-TO ( 

LANGUAGE , "English" ) ) (155) 

Epistemonikos

Date searched: February 10, 2020 

advanced_title_en:(TBI OR mTBI OR bTBI OR (trauma OR traumatic OR posttraumatic OR 

post-traumatic ) AND ( brain OR crania* OR cranio* OR cerebr* OR cortex OR cortical OR 

head* ) OR concussion* OR concussive OR "minor brain" OR "minor head" OR postconcuss*) 

AND advanced_title_en:(arthritis OR chronic OR "complex regional" OR crps OR fibromyalgia 

OR gout OR headache OR migraine OR myalgia OR neuralgia OR neuropathy OR nociceptive 

OR osteoarthritis OR osteo-arthritis OR phantom limb OR spondylosis OR centralized pain OR 

central sensitization OR intractable OR long-term OR longer-term OR noncancer OR non-cancer 

OR nonmalignant OR non-malignant OR persistent OR refractory) NOT 

advanced_title_en:(adolescent OR adolescents OR adolescence OR child OR children OR 

childhood OR juvenile OR pediatric OR paediatric OR preschool OR pre-school OR school-age 

OR teen OR teens OR teenager OR teenagers OR youth OR youths) [Filters: 

classification=systematic-review, protocol=no, cochrane=missing, pmc=without] (109) 

ClinicalTrials.gov 

Date searched: February 10, 2020 

( arthritis OR chronic fatigue OR complex regional pain OR crps OR fibromyalgia OR gout OR 

headache OR migraine OR myalgia OR neuralgia OR neuropathy OR nociceptive OR 

osteoarthrits OR osteo-arthritis OR phantom limb OR post-traumatic headache OR reflex 

sympathetic dystrophy OR spondylosis OR central pain OR centralized pain OR centralized 

sensitivity OR chronic pain OR intractable pain OR long-term pain OR longer-term pain OR 

noncancer pain OR non-cancer pain OR nonmalignant pain OR non-malignant pain OR

persistent pain OR refractory pain ) | TBI OR mTBI OR bTBI OR (trauma* OR posttraumatic 

OR post-traumatic ) AND ( brain OR crania* OR cranio* OR cerebr* OR cortex OR cortical OR 

head*) OR concussion* OR concussive OR contrecoup OR coup-contrecoup OR 

EXPAND[Concept] "minor brain" OR EXPAND[Concept] "minor head" OR postconcuss* | 

Adult, Older Adult (210) 

WHO ICTRP

Date searched: February 10, 2020 

Title=TBI OR mTBI OR bTBI OR (trauma OR traumatic OR posttraumatic OR post-traumatic) 

AND (brain OR crania* OR cranio* OR cerebr* OR cortex OR cortical OR head*) OR 

concussion* OR concussive OR "minor brain" OR "minor head" OR postconcuss* 

Condition=arthritis OR chronic OR "complex regional" OR crps OR fibromyalgia OR gout OR 

headache OR migraine OR myalgia OR neuralgia OR neuropathy OR nociceptive OR 

osteoarthritis OR osteo-arthritis OR phantom limb OR reflex sympathetic dystrophy OR 

spondylosis OR centralized pain OR central sensitization OR intractable OR long-term OR 

longer-term OR noncancer OR non-cancer OR nonmalignant OR non-malignant OR persistent 

OR refractory (without synonyms checked) 

Recruitment status=ALL (140) 
Chronic Pain and mTBI Evidence Synthesis Program

90

Google Scholar 

Date searched: February 10, 2020 

2 separate searches were conducted, reviewed first 10 pages of results for each

(TBI OR mTBI OR "traumatic brain" OR concussion OR "minor brain" OR "minor head" OR 

postconcuss*) AND (pain OR central sensitization OR intractable OR long-term OR noncancer 

OR non-cancer OR nonmalignant OR non-malignant OR persistent OR refractory)

(TBI OR mTBI OR "traumatic brain" OR concussion OR "minor brain" OR "minor head" OR 

postconcussion) AND (chronic OR intractable OR long-term OR persistent OR refractory) AND 

(treatment OR management OR intervention) 

(10) 
Chronic Pain and mTBI Evidence Synthesis Program

91

APPENDIX B. STUDY SELECTION

Inclusion/Exclusion Criteria for Full Text Review

VA-ESP Chronic Pain in Veterans and Servicemembers with a History of Mild Traumatic Brain 

Injury

1. Language: Is the full text of the article in English?

Yes  Proceed to #2

No  Code X1. STOP

2. Publication type: Is this a published study (exclude: dissertations, conference abstracts, 

protocols, unpublished results, letters, reviews, etc)?

Yes  Proceed to #3

No  Code X2. Add code B (example: X2 – B) if retaining for background/discussion. 

STOP

3. Population: Does the study include adult Veterans or Servicemembers with chronic pain 

and a history of mTBI?

Definitions: Pain: Include headaches/migraines. Chronic>3 months. Assume chronic 

unless explicitly says acute. mTBI: If mixed TBI population (eg mild, mod, and or 

severe), only include if mTBI results are reported separately. Include concussion. “Postconcussive symptoms” okay only if there’s confirmation of mTBI or concussion that 

caused the symptoms (eg, a sample of recently returned Vets who complete the NSI and 

score 20 or higher does NOT qualify unless the study specifies that they all had a 

concussion or mTBI).

Yes  Proceed to #4

No  Code X3. Add code B if retaining for background/discussion. STOP

4. Population: Is this a U.S. population?

Yes  Proceed to #5

No, they’re international  Does it appear to address benefits and harms of interventions 

to treat chronic pain in Veterans or Servicemembers with a history of mTBI (KQ3)?

Yes  Proceed to #5

No  Code X3. STOP

5. Intervention: Is the study examining pharmacologic, nonpharmacologic, or 

complementary and integrative health interventions to treat chronic pain in Veterans or 

Servicemembers with a history of mTBI (KQ3)?

Yes  Proceed to #8

No, not a treatment/intervention study  Proceed to #6.

No, not treating chronic pain  Code X5
Chronic Pain and mTBI Evidence Synthesis Program

92

6. Study design: Does the study report prevalence of chronic pain in the population of 

interest? 

Yes, reports prevalence  Proceed to #7 

No  Code X6

7. KQ2: Does this study report the prevalence of suicide-related outcomes (including 

suicide, suicidal ideation/intent/plan, and suicidal self-directed harm) in Veterans or 

Servicemembers with chronic pain and a history of mTBI?

Yes  Code 1 for KQ2. Proceed to #8 

No  Proceed to #8 

8. Study design: Is this an RCT, NRCT, cohort, prospective, or retrospective study 

(Exclude: Case studies/reports, cross-sectional, modeling studies)?

Yes  Proceed to #9 

No  but it does have at least 1 KQ coded. STOP. 

No  and it has no previous code. Code X6

9. Comparators: Is the comparator population 1 of the following: Placebo, active 

comparator, usual care, wait-list control, pre-post? Note: KQ1 and 1c do not require 

comparator, proceed to #11. 

Yes  Proceed to #10 

No  Code X4

10. Outcomes: does the study report benefits (eg reduced pain, mental health 

diagnosis/symptoms, opioid use; better QOL, functioning, treatment adherence) or harms 

(eg AEs, SAEs, withdrawals due to AEs) outcomes for chronic pain in 

Veterans/Servicemembers with history of mTBI measured by a validated tool?

Yes  Code 1 for KQ3. STOP

No  Code X5. STOP

Codes Key:

X1: Not English-language 

X2: Excluded publication type 

X3: Excluded population 

X4: Excluded comparator 

X5: No outcomes of interest 

X6: Excluded study design 
Chronic Pain and mTBI Evidence Synthesis Program

93

APPENDIX C. QUALITY ASSESSMENT

Table 10. Criteria used in quality assessment of randomized controlled trials

Cochrane RoB 2.0:33 Five domains through which bias may be introduced

1. Risk of bias arising from the randomization process:

1.1. Was the allocation sequence random?

1.2. Was the allocation sequence concealed until participants were enrolled and assigned to 

interventions?

1.3. Did baseline differences between intervention groups suggest a problem with the 

randomization process?

2. Risk of bias due to deviations from the intended interventions (effect of assignment to intervention):

2.1. Were participants aware of their assigned intervention during the trial?

2.2. Were carers and people delivering the interventions aware of participants' assigned 

intervention during the trial?

2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose 

because of the experimental context?

2.4. If Y/PY to 2.3: Were these deviations from intended intervention balanced between groups?

2.5. If N/PN/NI to 2.4: Were these deviations likely to have affected the outcome? 

2.6. Was an appropriate analysis used to estimate the effect of assignment to intervention? 

2.7. If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to 

analyze participants in the group to which they were randomized?

3. Risk of bias due to missing outcome data:

3.1. Were data for this outcome available for all, or nearly all, participants randomized? 

3.2. If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data? 

3.3. If N/PN to 3.2: Could missingness in the outcome depend on its true value? 

3.4. If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?

4. Risk of bias in measurement of the outcome:

4.1. Was the method of measuring the outcome inappropriate? 

4.2. Could measurement or ascertainment of the outcome have differed between intervention 

groups? 

4.3. If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study 

participants ? 

4.4. If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of 

intervention received? 

4.5. If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of 

intervention received?

5. Risk of bias in selection of the reported result:

5.1. 5.1 Were the data that produced this result analyzed in accordance with a pre-specified 

analysis plan that was finalized before unblinded outcome data were available for analysis? 

Is the numerical result being assessed likely to have been selected, on the basis of the results, from... 

5.2. ...multiple outcome measurements (eg scales, definitions, time points) within the outcome 

domain? 

5.3. ...multiple analyses of the data?

Overall risk-of-bias judgement

Low ROB The study is judged to be at low risk of bias for all domains for this result. 

Some Concerns The study is judged to raise some concerns in at least 1 domain for this result, but 

not to be at high risk of bias for any domain.

High ROB The study is judged to be at high risk of bias in at least 1 domain for this result. 

OR 

The study is judged to have some concerns for multiple domains in a way that 

substantially lowers confidence in the result.

Abbreviations: NI=not indicated; N=no; PN=probably not; PY=probably yes; ROB=risk of bias; Y=yes
Chronic Pain and mTBI Evidence Synthesis Program

94

Table 11. Quality ratings for studies reporting prevalence of chronic pain in 

Veterans/Servicemembers with history of mild traumatic brain injury

Study

Author, year

#1 #2 #3 #4 Overall study quality/Quality 

concerns

Applicability

BeswickEscanlar, 

201645

1 NA 0 0 Entire population of SMs and focused 

on incident mTBI with incident 

headache or migraine pain (no 

diagnosis codes prior to study start 

date) during 1-year follow-up period. 

Both mTBI and pain were defined as 

≥1 diagnosis code.

Post-9/11 SMs receiving 

military health care 

between 2006 and 2015.

Brickell, 

201442

1 0 0 0 Small sample size, and different

patients at each follow-up. High 

attrition; no report of non-responder 

characteristics. mTBI definition 

inconsistent with VA-DoD common 

definition (required LOC<15 minutes 

and allowed intracranial abnormality). 

Non-standard pain measure (based 

on open-ended telephone interview 

questions).

Post-9/11 SMs with mTBI 

and polytrauma.

Couch, 201646 0 0 1 0 Small sample size; highly selective 

patient group treated in 1 

reintegration clinic. mTBI assessed 

clinically according to VA/DoD 

common definition. Headache or 

migraine pain self-reported based on 

clinical assessment questionnaire.

Male, Post-9/11 Veterans 

at 1 site, between ages 

of 20 and 60, enrolled in 

reintegration clinic.

FarrellCarnahan, 

201547

1 0 1 1 Small study of Post-9/11 Veterans 

admitted to inpatient rehabilitation at 1 

of 4 VA polytrauma rehabilitation 

centers and enrolled in TBI Model 

Systems. mTBI assessed using TBI 

Model Systems form. Headache 

intensity assessed using single item 

from NSI. Differences between 

participants (80% of those recruited) 

and non-participants (20% of 

recruited) are unclear.

Post-9/11 Veterans 

requiring inpatient 

rehabilitation for TBI and 

who enroll in VA TBI 

Model Systems. 

Hoge, 200815 1 0 0 1 Survey with 59% response rate, no 

information on non-respondents. 

mTBI assessed using screening 

questions; mTBI group included n=4 

with LOC>30 mins. Pain measures 

assessed using validated instrument.

Post-9/11 Army SMs 

shortly after return from 

combat deployment.

Hoot, 201841† 1 0 1 1 Fairly selective study sample from 4 

sites (no information on Veterans/SMs 

who were recruited but did not enroll). 

Standardized and validated measures 

of mTBI and pain were used. 

Post-9/11 Veterans/SMs

with combat exposure 

enrolled in a 

comprehensive 

longitudinal study.

Jackson, 

201648

1 0 1 0 Veterans sampled nationally. mTBI 

assessed using VA 4-item screen plus 

Post-9/11 Veterans who 

received mental health 
Chronic Pain and mTBI Evidence Synthesis Program

95

Study

Author, year

#1 #2 #3 #4 Overall study quality/Quality 

concerns

Applicability

clinical interview. Headache pain 

assessed using post-concussive 

symptom indicators on VA 4-item 

screen.

evaluation in VA; 

oversampled females 

and Veterans with PTSD. 

King, 201440 1 NA 0 0 Entire population of VA users across 

region. mTBI defined using ≥1 ICD 

diagnosis code for post-concussion 

syndrome. Pain conditions also based 

on ICD diagnosis codes.

Post-9/11 Veterans who 

used VA primary care in 

VISN 2.

Kulas, 201639 1 NA 0 0 Large study that included full 

population of patients from VA for 1 

year. Both mTBI and pain conditions 

based on presence of ≥1 ICD 

diagnosis code during study period.

Post-9/11 Veterans 

receiving VA care in 

fiscal year 2012.

Lew, 200925* 0 NA 1 1 Single site; chart review of all patients 

assessed for 22 months. No 

demographics provided. mTBI and 

general chronic pain defined as 

clinician documentation in CTBIE 

chart note but making assumption that 

post-concussive symptoms 

associated only with mTBI and not 

TBI of greater severity.

Post-9/11 Veterans 

treated at single Level 2 

polytrauma clinic.

MacGregor, 

201349

1 NA 0 0 Fairly small multi-site sample but 

representative of population 

described. mTBI measurement based 

on ICD codes and include 1 that 

would be categorized as ‘moderate’ 

using VA/DoD common definition. 

Pain assessment not validated but 

standard.

Post-9/11 SMs that incur 

minor-to-moderate 

deployment injuries as 

recorded in deployment 

healthcare database and 

complete both PDHA and 

PDHRA within 1-year 

post-deployment.

Patil, 201150* 0 NA 1 0 Consecutive patients from a single VA 

polytrauma site. mTBI assessed using 

CTBIE. Headache pain assessed 

using question on CTBIE and 

referral/follow-up at Neurology clinic.

Post-9/11 Veterans 

receiving care in a single 

VA (polytrauma network 

site).

Powell, 201543 1 0 1 0 Fairly selective study sample from 1 

site (no information on Veterans/SMs 

who were recruited but did not enroll). 

mTBI based on clinical interview and 

consensus among PhD-level 

psychologists. General pain 

assessment non-standard. 

Post-9/11 Veterans

receiving VA care in 

Boston that would enroll 

in TRACTS longitudinal 

study. 

Pugh, 20197 1 NA 1 0 Entire population of VA users. mTBI 

defined using complex algorithm 

taking many data sources into 

account. Pain conditions based on 

ICD diagnosis codes.

Post-9/11 Veterans who 

enrolled in and used VA 

healthcare.

Romesser, 

201244

0 NA 1 0 Fairly selective study sample from 2 

polytrauma sites. mTBI and pain 

assessed from patient self-reported 

Post-9/11 Veterans 

assessed in 2 VA 

polytrauma clinics.
Chronic Pain and mTBI Evidence Synthesis Program

96

Study

Author, year

#1 #2 #3 #4 Overall study quality/Quality 

concerns

Applicability

clinical questionnaire; unclear if 

standardized or validated.

Ruff, 20086 1 NA 1 0 Fairly small sample of consecutive 

patients at VA polytrauma clinic. mTBI 

assessed clinically and defined using 

VA-DoD standard definition. 

Headache pain measures were selfreported; focused on deploymentrelated headaches.

Post-9/11 Veterans 

seeking care for TBI at 

VA with blast-related 

mTBI.

Schwab, 

201751

1 1 1 1 Sampled from among SMs with 

positive mTBI screen at 2 sites; used 

structured interview to confirm mTBI 

history. Headache intensity assessed 

using NSI. Excluded participants with 

potential symptom exaggeration. Loss 

to follow-up of 34%; compared 

responders to non-responders and 

reported few differences.

Post-9/11 Army soldiers 

with Iraq/Afghanistan 

deployment history from 

2 military sites. 

Seal, 20174* 1 NA 1 1 Large study of entire patient 

population; mTBI assessed using 

CTBIE; General chronic pain 

assessed using ICD diagnosis codes,

but pain interference assessed using 

standardized measure from CTBIE.

Post-9/11 Veterans who 

use VA and completed 

CTBIE.

Suri, 201753* 1 0 1 1 Large multi-site sample of VA users 

that completed CTBIE, considered 

gold standard assessment for mTBI. 

Pain measures standard and/or 

validated (pain interference question 

from NSI). 

Post-9/11 Veterans who 

use VA and completed 

CTBIE.

Suri, 201952* 1 NA 1 0 Large multi-site population of VA 

users that completed CTBIE, 

considered gold standard assessment 

for mTBI; pain assessed using “pain 

location” measure on CTBIE. Large 

proportion of Veterans excluded 

because of missing data. 

Post-9/11 Veterans who 

use VA and completed 

CTBIE.

Theeler, 

201254

0 0 1 0 Participants from 1 site; enrolled 

based on positive mTBI screen but

presumed confirmed in TBI clinic. 

Demographics not reported. Unknown 

if pain measure was standardized or 

validated. 

Post-9/11 SMs who had 

a deployment-related 

concussion in Iraq or 

Afghanistan. 

Tsao, 201755 1 0 0 0 Sample of post-deployment SMs from 

3 sites; unclear what proportion of 

recruited SMs participated and how 

responders differed from nonresponders. mTBI assessed using 

screening questions (VA-DoD 

common definition). Headache pain 

assessed using nonPost-9/11 male Marines 

returning from 

Iraq/Afghanistan

deployments at 1 of 3 

sites in the US.
Chronic Pain and mTBI Evidence Synthesis Program

97

Study

Author, year

#1 #2 #3 #4 Overall study quality/Quality 

concerns

Applicability

standardized/validated item(s) on 

questionnaire. 

Vanderploeg, 

200956

1 0 0 0 Random-sample and in-person 

assessments. No description of nonrespondents. Non-standard measures 

of mTBI and pain.

Male Vietnam-era Army 

Veterans. 

Walker, 

201857†

1 0 1 1 Fairly selective study sample from 4 

sites (no information on Veterans/SMs 

who were recruited but did not enroll). 

Standardized and validated measures 

of mTBI and pain were used. 

Post-9/11 Veterans/SMs

with combat exposure 

enrolled in a 

comprehensive 

longitudinal study.

Webb, 201558 1 NA 0 0 Entire population of Military Health 

System users across multiple sites. 

mTBI defined using CDCrecommended series of ICD diagnosis 

codes. Headache and migraine pain 

based on ICD diagnosis codes.

Post-9/11 Air Force SMs 

who used Military Health 

System between 2001

and 2008. 

Wilk, 201060 1 0 0 1 Survey from single-site with 57% 

response rate, no information on nonrespondents. mTBI assessed using 

screening questions. Pain measures 

assessed using validated instrument

(PHQ-15). Bivariable analyses only in 

blast/non-blast comparisons.

Post-9/11 Army SMs 

shortly after return from 

high-combat deployment.

Wilk, 201259 1 0 0 1 Survey from single site with 73% 

response rate, no information on nonrespondents. mTBI assessed using 

screening questions. Pain measures 

assessed using validated instrument

(PHQ-15). 

Post-9/11 Army SMs 

shortly after return from 

combat deployment.

*Study based on VA Comprehensive TBI Evaluation (CTBIE) data. †Chronic Effects of Neurotrauma Consortium 

(CENC) longitudinal cohort study.

Abbreviations: CDC=Centers for Disease Control and Prevention; CTBIE=Clinical TBI Evaluation; 

DoD=Department of Defense; ICD=International Classification of Diseases; mTBI=Mild Traumatic Brain Injury;

SMs=Servicemembers; VA=Veterans Affairs; VISN=Veterans Integrated Services Network; PTSD=Posttraumatic 

stress disorder; NA=Not applicable

Quality Assessment Criteria

1. Representativeness of the sample:

1=Truly representative of the target population

1=Somewhat representative of the target population 

0=Selected subset of Veterans/SMs

0=No

2. Non-respondents/non-enrolled:

Enter 0 or 1:

1=Comparability between respondent and non-respondent characteristics is established; 

response rate is satisfactory

0=Comparability between respondents and non-respondents is unsatisfactory; response 
Chronic Pain and mTBI Evidence Synthesis Program

98

rate is unsatisfactory

0=No description of the characteristics of the responders versus non-responders; no 

description of response rate

NA=EHR studies (patient does not opt in versus opt out) 

3. Were objective, standard criteria used for measurement of mTBI?

Enter 0 or 1:

1=Validated measures (eg any that uses VA/DoD common definition with clinical 

interview)

0=Administrative codes 

0=Non-validated (eg, reported concussion, self-report, initial screen)

4. Were standard, validated criteria used for measurement of chronic pain?

Enter 0 or 1: 

a) All measures standard and/or validated? (if some are validated and some are not, note 

which get 1 or 0) 

1=yes 

0=no, self-report measure; not validated for chronic pain measurement

0=no, proxy measure used (eg, opioid medication use) 
Chronic Pain and mTBI Evidence Synthesis Program

99

APPENDIX D. STUDIES EXCLUDED AT FULL TEXT LEVEL

Excluded publication type

Barrett RS. Post-traumatic headache. Combat soldiers are suffering. Adv NPs PAs. 

2012;3(1):33-34. 

Bell KR, Brockway JA, Fann JR, et al. Concussion treatment after combat trauma: 

development of a telephone based, problem solving intervention for service members. Contemp 

Clin Trials. 2015;40:54-62. 

Daggett V. Feasibility and satisfaction with the VETeranS Compensate, Adapt, REintegrate 

(VETS-CARE) intervention. Brain Inj. 2014;28(5-6):554. 

DePalma RG. Combat TBI: History, Epidemiology, and Injury Modes. CRC Press/Taylor & 

Francis. 2015;2. 

Eskridge SL. Combat-related blast injuries: Injury types and outcomes. Dissertation Abstracts 

International: Section B: The Sciences and Engineering. 2012;72(7-B):3929. 

Finkel A. Headaches in soldiers with mild traumatic brain injury--additional data. Headache. 

2012;52(8):1320. 

Gelinas C. Validation of a revised pain assessment tool for brain-injured ICU patients. Critical 

care medicine Conference: 46th critical care congress of the society of critical care medicine, 

SCCM. 2016;44(12 Supplement 1):269. 

Hoffer ME, Donaldson C, Gottshall KR, Balaban C, Balough BJ. Blunt and blast head trauma: 

different entities. Int Tinnitus J. 2009;15(2):115-118. 

Hoffman JM, Ehde DM, Dikmen S, et al. Telephone-delivered cognitive behavioral therapy for 

veterans with chronic pain following traumatic brain injury: Rationale and study protocol for a 

randomized controlled trial study. Contemp Clin Trials. 2019;76:112-119. 

Khoury S, Benavides R. Pain with traumatic brain injury and psychological disorders. Prog 

Neuropsychopharmacol Biol Psychiatry. 2018;87(Pt B):224-233. 

Kjeldgaard D, Forchhammer H, Jensen R. Cognitive, emotional and somatic symptoms among 

patients with chronic posttraumatic headache. A controlled study...The European Headache and 

Migraine Trust International Congress, London, UK. 20-23 September 2012. J Headache Pain. 

2013;14:1-1. 

Kumar A, Loane DJ. Neuroinflammation after traumatic brain injury: opportunities for 

therapeutic intervention. Brain, behavior, and immunity. 2012;26(8):1191-1201. 
Chronic Pain and mTBI Evidence Synthesis Program

100

Malozzi SL. Predicting clinical outcomes in OEF/OIF/OND veterans with the polytrauma 

clinical triad. Dissertation Abstracts International: Section B: The Sciences and Engineering. 

2019;80(2-B(E)):No-Specified. 

Mehalick ML, Glueck AC. Examining the relationship and clinical management between 

traumatic brain injury and pain in military and civilian populations. Brain Inj. 

2018;32(11):1307-1314. 

Metti A. Post-traumatic vs non-traumatic headaches: a phenotypic analysis. Neurology. 

2018;90(15). 

Nassif TH. Examining the effectiveness of mindfulness meditation for chronic pain 

management in combat Veterans with traumatic brain injury. Dissertation Abstracts 

International: Section B: The Sciences and Engineering. 2014;75(3-B(E)):No-Specified. 

NCT00862095. Medical Therapies for Chronic Post-Traumatic Headaches. A Randomized 

Controlled Trial of Medical Therapies for Chronic Post-Traumatic Headaches. 2009.

NCT01306968. Hyperbaric Oxygen Therapy (HBO2) for Persistent Post-concussive Symptoms 

After Mild Traumatic Brain Injury (mTBI). In. Research USAM, Materiel Command Y, 

trans2011. 

NCT01611194. mTBI Mechanisms of Action of HBO2 for Persistent Post-Concussive 

Symptoms. In. Research USAM, Materiel Command Y, trans2012. 

O'Connor KL. Concussion among military service academy members: Identifying risk factors, 

recovery trajectories, and the role of mental health. Dissertation Abstracts International: 

Section B: The Sciences and Engineering. 2018;79(12-B(E)):No-Specified. 

Ruff RL, Riechers RG, Ruff SS. Relationships between mild traumatic brain injury sustained in 

combat and post-traumatic stress disorder. F1000 Med Rep. 2010;2:64. 

Saper RB, Lemaster CM, Elwy AR, et al. Yoga versus education for Veterans with chronic low 

back pain: study protocol for a randomized controlled trial. Trials. 2016;17(1):224. 

Tang V, Warden J, Cullen N, Rutledge E. Topiramate in traumatic brain injury: Adverse effects 

on cognitive function. The Journal of Head Trauma Rehabilitation. 2007;22(6):409-410. 

Tepper D. Post-traumatic headache in veterans. Headache. 2013;53(5):875-876.

Theeler B, Lucas S, Riechers RG, 2nd, Ruff RL. Post-traumatic headaches in civilians and 

military personnel: a comparative, clinical review. Headache. 2013;53(6):881-900. 

Wortman K. Personality and executive functioning in male veterans with mild traumatic brain 

injury. Dissertation Abstracts International: Section B: The Sciences and Engineering. 

2018;79(1-B(E)):No-Specified. 
Chronic Pain and mTBI Evidence Synthesis Program

101

Zhang K, Jiang W, Ma T, Wu H. Comparison of early and late decompressive craniectomy on 

the long-term outcome in patients with moderate and severe traumatic brain injury: A metaanalysis. Br J Neurosurg. 2016;30(2):251-257. 

Excluded population

Adams RS, Larson MJ, Meerwijk EL, Williams TV, Harris AHS. Postdeployment Polytrauma 

Diagnoses Among Soldiers and Veterans Using the Veterans Health Affairs Polytrauma 

System of Care and Receipt of Opioids, Nonpharmacologic, and Mental Health Treatments. J 

Head Trauma Rehabil. 2019;34(3):167-175. 

Afari N, Pittman J, Floto E, et al. Differential impact of combat on postdeployment symptoms 

in female and male veterans of Iraq and Afghanistan. Mil Med. 2015;180(3):296-303. 

Arbisi PA, Polusny MA, Erbes CR, Thuras P, Reddy MK. The Minnesota Multiphasic 

Personality Inventory-2 Restructured Form in National Guard soldiers screening positive for 

posttraumatic stress disorder and mild traumatic brain injury. Psychol Assess. 2011;23(1):203-

214. 

Avallone KM, Smith ER, Ma S, et al. PTSD as a Mediator in the Relationship Between PostConcussive Symptoms and Pain Among OEF/OIF/OND Veterans. Mil Med. 2019;184(1-

2):e118-e123. 

Balba NM, Elliott JE, Weymann KB, et al. Increased Sleep Disturbances and Pain in Veterans 

with Comorbid Traumatic Brain Injury and Posttraumatic Stress Disorder. J Clin Sleep Med. 

2018;14(11):1865-1878. 

Bertenthal D, Yaffe K, Barnes DE, et al. Do postconcussive symptoms from traumatic brain 

injury in combat veterans predict risk for receiving opioid therapy for chronic pain? Brain Inj. 

2018;32(10):1188-1196. 

Blakey SM, Wagner HR, Naylor J, et al. Chronic Pain, TBI, and PTSD in Military Veterans: A 

Link to Suicidal Ideation and Violent Impulses? J Pain. 2018;19(7):797-806. 

Bomyea J, Lang AJ, Delano-Wood L, et al. Neuropsychiatric Predictors of Post-Injury 

Headache After Mild-Moderate Traumatic Brain Injury in Veterans. Headache. 

2016;56(4):699-710. 

Bryan CJ, Hernandez AM. Predictors of post-traumatic headache severity among deployed 

military personnel. Headache. 2011;51(6):945-953. 

Bushnik T, Englander J, Wright J. The experience of fatigue in the first 2 years after moderateto-severe traumatic brain injury: a preliminary report. J Head Trauma Rehabil. 2008;23(1):17-

24. 
Chronic Pain and mTBI Evidence Synthesis Program

102

Carlozzi NE, Kisala PA, Boulton AJ, et al. Measuring Pain in TBI: Development of the TBIQOL Pain Interference Item Bank and Short Form. Arch Phys Med Rehabil. 2020;101(1):11-

19. 

Carlson KF, Taylor BC, Hagel EM, Cutting A, Kerns R, Sayer NA. Headache diagnoses among 

Iraq and Afghanistan war veterans enrolled in VA: a gender comparison. Headache. 

2013;53(10):1573-1582. 

Cifu DX, Taylor BC, Carne WF, et al. Traumatic brain injury, posttraumatic stress disorder, 

and pain diagnoses in OIF/OEF/OND Veterans. J Rehabil Res Dev. 2013;50(9):1169-1176. 

Cohen SP, Plunkett AR, Wilkinson I, et al. Headaches during war: analysis of presentation, 

treatment, and factors associated with outcome. Cephalalgia. 2012;32(2):94-108. 

Combs MA, Critchfield EA, Soble JR. Relax while you rehabilitate: A pilot study integrating a 

novel, yoga-based mindfulness group intervention into a residential military brain injury 

rehabilitation program. Rehabil Psychol. 2018;63(2):182-193. 

Copeland LA, Finley EP, Bollinger MJ, Amuan ME, Pugh MJ. Comorbidity Correlates of 

Death Among New Veterans of Iraq and Afghanistan Deployment. Med Care. 

2016;54(12):1078-1081. 

Davis L, Hanson B, Gilliam S. Pilot study of the effects of mixed light touch manual therapies 

on active duty soldiers with chronic post-traumatic stress disorder and injury to the head. J 

Bodywork Mov Ther. 2016;20(1):42-51. 

Denby E, Murphy D, Busuttil W, Sakel M, Wilkinson D. Neuropsychiatric Outcomes in UK 

Military Veterans with Mild Traumatic Brain Injury and Vestibular Dysfunction. J Head 

Trauma Rehabil. 2020;35(1):57-65. 

Detweiler MB, Arif S, Candelario J, et al. Salem VAMC-U.S. Army Fort Bragg Warrior 

Transition Clinic telepsychiatry collaboration: 12-month operation clinical perspective. 

Telemed J E Health. 2012;18(2):81-86.

Eagle SR, Kontos AP, Mi QI, et al. Shared Neuromuscular Performance Traits in Military 

Personnel with Prior Concussion. Med Sci Sports Exerc. 2019;51(8):1619-1625. 

Elbogen EB, Alsobrooks A, Battles S, et al. Mobile Neurofeedback for Pain Management in 

Veterans with TBI and PTSD. Pain Med. 2019;07:07. 

Elnitsky CA, Blevins C, Findlow JW, Alverio T, Wiese D. Student Veterans Reintegrating 

from the Military to the University With Traumatic Injuries: How Does Service Use Relate to 

Health Status? Arch Phys Med Rehabil. 2018;99(2S):S58-S64.

Epstein EL, Martindale SL, Va Mid-Atlantic Mirecc W, Miskey HM. Posttraumatic stress 

disorder and traumatic brain Injury: Sex differences in veterans. Psychiatry Research. 

2019;274:105-111. 
Chronic Pain and mTBI Evidence Synthesis Program

103

Eskridge SL, Macera CA, Galarneau MR, et al. Influence of combat blast-related mild 

traumatic brain injury acute symptoms on mental health and service discharge outcomes. J 

Neurotrauma. 2013;30(16):1391-1397. 

Finkel AG, Yerry JA, Klaric JS, Ivins BJ, Scher A, Choi YS. Headache in military service 

members with a history of mild traumatic brain injury: A cohort study of diagnosis and 

classification. Cephalalgia. 2017;37(6):548-559. 

Finley EP, Bollinger M, Noel PH, et al. A national cohort study of the association between the 

polytrauma clinical triad and suicide-related behavior among US Veterans who served in Iraq 

and Afghanistan. Am J Public Health. 2015;105(2):380-387. 

Fonda JR, Gradus JL, Brogly SB, McGlinchey RE, Milberg WP, Fredman L. Traumatic Brain 

Injury and Opioid Overdose Among Post-9/11 Veterans with Long-Term Opioid Treatment of 

Chronic Pain. J Head Trauma Rehabil. 2019;08:08. 

Golub A, Bennett AS. Prescription opioid initiation, correlates, and consequences among a 

sample of OEF/OIF military personnel. Subst Use Misuse. 2013;48(10):811-820. 

Harch PG, Andrews SR, Fogarty EF, Lucarini J, Van Meter KW. Case control study: 

hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion 

syndrome and post-traumatic stress disorder. Medical Gas Research. 2017;7(3):156-174. 

Hershaw JN, Hill-Pearson CA, Arango JI, Souvignier CAR, Pazdan CRM. Semi-Automated 

Neurofeedback Therapy for Persistent Postconcussive Symptoms in a Military Clinical Setting: 

A Feasibility Study. Mil Med. 2019;11:11. 

Higgins DM, Kerns RD, Brandt CA, et al. Persistent pain and comorbidity among Operation 

Enduring Freedom/Operation Iraqi Freedom/operation New Dawn veterans. Pain Med. 

2014;15(5):782-790. 

Higgins DM. Internet-based Pain Self-management for Veterans: Feasibility and Preliminary 

Efficacy of the Pain EASE Program. In.

Hoffman SN, Herbert MS, Crocker LD, et al. The Role of Pain Catastrophizing in Cognitive 

Functioning Among Veterans with a History of Mild Traumatic Brain Injury. J Head Trauma 

Rehabil. 2019;34(4):E61-E66. 

Howard L, Dumkrieger G, Chong CD, Ross K, Berisha V, Schwedt TJ. Symptoms of 

Autonomic Dysfunction Among Those with Persistent Posttraumatic Headache Attributed to 

Mild Traumatic Brain Injury: A Comparison to Migraine and Healthy Controls. Headache. 

2018;58(9):1397-1407. 

Hudson TJ, Painter JT, Gressler LE, et al. Factors Associated with Opioid Initiation in 

OEF/OIF/OND Veterans with Traumatic Brain Injury. Pain Med. 2018;19(4):774-787. 
Chronic Pain and mTBI Evidence Synthesis Program

104

Hudson TJ, Painter JT, Martin BC, et al. Pharmacoepidemiologic analyses of opioid use among 

OEF/OIF/OND veterans. Pain. 2017;158(6):1039-1045. 

Jaramillo CA, Cooper DB, Wang CP, et al. Subgroups of US IRAQ and Afghanistan veterans: 

associations with traumatic brain injury and mental health conditions. Brain Imaging Behav. 

2015;9(3):445-455. 

Jaramillo CA, Eapen BC, McGeary CA, et al. A cohort study examining headaches among 

veterans of Iraq and Afghanistan wars: Associations with traumatic brain injury, PTSD, and 

depression. Headache. 2016;56(3):528-539. 

Johansson B, Wentzel AP, Andréll P, Mannheimer C, Rönnbäck L. Methylphenidate reduces 

mental fatigue and improves processing speed in persons suffered a traumatic brain injury. 

Brain Inj. 2015;29(6):758-765. 

Johnson SS, Levesque DA, Broderick LE, Bailey DG, Kerns RD. Pain Self-Management for 

Veterans: Development and Pilot Test of a Stage-Based Mobile-Optimized Intervention. JMIR 

Med Inform. 2017;5(4):e40. 

Jonas WB, Bellanti DM, Paat CF, et al. A Randomized Exploratory Study to Evaluate Two 

Acupuncture Methods for the Treatment of Headaches Associated with Traumatic Brain Injury. 

Med Acupunct. 2016;28(3):113-130. 

Jouzdani SR, Ebrahimi A, Rezaee M, Shishegar M, Tavallaii A, Kaka G. Characteristics of 

posttraumatic headache following mild traumatic brain injury in military personnel in Iran. 

Environ. 2014;19(6):422-428. 

King PR, Beehler GP, Wade MJ. Self-Reported Pain and Pain Management Strategies Among 

Veterans with Traumatic Brain Injury: A Pilot Study. Mil Med. 2015;180(8):863-868. 

Kjeldgaard Nielsen D FHTTWJRH. EHMTI-0162. Cognitive behavioural treatment for the 

chronic posttraumatic headache patient: a randomised controlled trial. Journal of headache and 

pain. 2014;15. 

Lang KP, Veazey-Morris K, Andrasik F. Exploring the role of insomnia in the relation between 

PTSD and pain in veterans with polytrauma injuries. J Head Trauma Rehabil. 2014;29(1):44-

53. 

Lee CJ, Felix ER, Levitt RC, et al. Traumatic brain injury, dry eye and comorbid pain 

diagnoses in US veterans. Br J Ophthalmol. 2018;102(5):667-673. 

Losoi H, Silverberg ND, Waljas M, et al. Resilience Is Associated with Outcome from Mild 

Traumatic Brain Injury. J Neurotrauma. 2015;32(13):942-949. 

Mahmood S, Al-Thani H, El-Menyar A, et al. Tramadol in traumatic brain injury: Should we 

continue to use it? Journal of Anaesthesiology Clinical Pharmacology. 2015;31(3):344-348. 
Chronic Pain and mTBI Evidence Synthesis Program

105

Martindale SL, Epstein EL, Taber KH, Workgroup VAM-AM, Rowland JA. Behavioral and 

Health Outcomes Associated with Deployment and Nondeployment Acquisition of Traumatic 

Brain Injury in Iraq and Afghanistan Veterans. Arch Phys Med Rehabil. 2018;99(12):2485-

2495. 

Miller RS, Weaver LK, Bahraini N, et al. Effects of hyperbaric oxygen on symptoms and 

quality of life among service members with persistent postconcussion symptoms: a randomized 

clinical trial. JAMA Intern Med. 2015;175(1):43-52.

Moeller DR, Duffey JM, Goolsby AM, Gallimore JT. Use of a Removable Mandibular 

Neuroprosthesis for the Reduction of Posttraumatic Stress Disorder (PTSD) and Mild 

Traumatic Brain Injury/PTSD/Associated Nightmares, Headaches, and Sleep Disturbances. J 

Spec Oper Med. 2014;14(3):64-73. 

Moriarty H, Winter L, Robinson K, et al. Exploration of Individual and Family Factors Related 

to Community Reintegration in Veterans with Traumatic Brain Injury. Journal of the American 

Psychiatric Nurses Association. 2015;21(3):195-211. 

Mortera MH, Kinirons SA, Simantov J, Klingbeil H. Long-Term Neurobehavioral Symptoms 

and Return to Productivity in Operation Enduring Freedom/Operation Iraqi Freedom Veterans 

with and Without Traumatic Brain Injury. Arch Phys Med Rehabil. 2018;99(2S):S50-S57. 

Norris JN, Smith S, Harris E, Labrie DW, Ahlers ST. Characterization of acute stress reaction 

following an IED blast-related mild traumatic brain injury. Brain Inj. 2015;29(7-8):898-904. 

Paltsev AI, Torgashov MN, Voronova YS, Bayandina EV, Lunyakina SB. Role of combat 

stress in the formation of chronic pain syndrome in combatants and its treatment with pantogam 

active. Neuroscience and Behavioral Physiology. 2011;41(8):878-882. 

Phillips KM, Clark ME, Gironda RJ, et al. Pain and psychiatric comorbidities among two 

groups of Iraq and Afghanistan era Veterans. J Rehabil Res Dev. 2016;53(4):413-432. 

Pugh MJ, Finley EP, Wang CP, et al. A retrospective cohort study of comorbidity trajectories 

associated with traumatic brain injury in veterans of the Iraq and Afghanistan wars. Brain Inj. 

2016;30(12):1481-1490. 

Ribeiro CJN, Araujo ACS, Brito SB, et al. Pain assessment of traumatic brain injury victims 

using the Brazilian version of the Behavioral Pain Scale. Revista Brasileira de Terapia 

Intensiva. 2018;30(1):42-49. 

Rosenthal JF, Erickson JC. Post-traumatic stress disorder in U.S. soldiers with post-traumatic 

headache. Headache. 2013;53(10):1564-1572. 

Sayer NA, Cifu DX, McNamee S, et al. Rehabilitation needs of combat-injured service 

members admitted to the VA Polytrauma Rehabilitation Centers: the role of PM&R in the care 

of wounded warriors. Pm R. 2009;1(1):23-28. 
Chronic Pain and mTBI Evidence Synthesis Program

106

Scott BR, Uomoto JM, Barry ES. Impact of Pre-Existing Migraine and Other Co-Morbid or 

Co-Occurring Conditions on Presentation and Clinical Course Following Deployment-Related 

Concussion. Headache. 2020;03:03.

Seal KH, Bertenthal D, Barnes DE, et al. Traumatic Brain Injury and Receipt of Prescription 

Opioid Therapy for Chronic Pain in Iraq and Afghanistan Veterans: Do Clinical Practice 

Guidelines Matter? J Pain. 2018;19(8):931-941. 

Shah A, Ayala M, Capra G, Fox D, Hoffer M. Otologic assessment of blast and nonblast injury 

in returning Middle East-deployed service members. Laryngoscope. 2014;124(1):272-277. 

Shan K, Cao W, Yuan Y, et al. Use of the critical-care pain observation tool and the bispectral 

index for the detection of pain in brain-injured patients undergoing mechanical ventilation: A 

STROBE-compliant observational study. Medicine (Baltimore). 2018;97(22):e10985-e10985. 

Sheng T, Fairchild JK, Kong JY, et al. The influence of physical and mental health symptoms 

on Veterans' functional health status. J Rehabil Res Dev. 2016;53(6):781-796. 

Stilling Jm PEMLJGLSWMAFDSPMODCT. Treatment of persistent post-traumatic headache 

and post-concussion symptoms using rTMS: a pilot, double-blind, randomized controlled trial. 

J Neurotrauma. 2019. 

Strigo IA, Spadoni AD, Inslicht SS, Simmons AN. Repeated Exposure to Experimental Pain 

Differentiates Combat Traumatic Brain Injury with and without Post-Traumatic Stress 

Disorder. J Neurotrauma. 2018;35(2):297-307. 

Strigo IA, Spadoni AD, Lohr J, Simmons AN. Too hard to control: compromised pain 

anticipation and modulation in mild traumatic brain injury. Transl Psychiatry. 2014;4:e340. 

Tan G, Fink B, Dao TK, et al. Associations among pain, PTSD, mTBI, and heart rate 

variability in veterans of Operation Enduring and Iraqi Freedom: a pilot study. Pain Med. 

2009;10(7):1237-1245. 

Taylor BC, Hagel EM, Carlson KF, et al. Prevalence and costs of co-occurring traumatic brain 

injury with and without psychiatric disturbance and pain among Afghanistan and Iraq War 

Veteran V.A. users. Med Care. 2012;50(4):342-346. 

Terrio H, Brenner LA, Ivins BJ, et al. Traumatic brain injury screening: preliminary findings in 

a US Army Brigade Combat Team. J Head Trauma Rehabil. 2009;24(1):14-23. 

Theeler BJ, Erickson JC. Mild head trauma and chronic headaches in returning US soldiers. 

Headache. 2009;49(4):529-534. 

Tschiffely AE, Haque A, Haran FJ, et al. Recovery from Mild Traumatic Brain Injury 

Following Uncomplicated Mounted and Dismounted Blast: A Natural History Approach. Mil 

Med. 2018;183(3-4):e140-e147. 
Chronic Pain and mTBI Evidence Synthesis Program

107

Van Pelt KL, Allred D, Cameron KL, et al. A cohort study to identify and evaluate concussion 

risk factors across multiple injury settings: findings from the CARE Consortium. Inj Epidemiol. 

2019;6(1):1. 

Vanderploeg RD, Belanger HG, Horner RD, et al. Health outcomes associated with military 

deployment: mild traumatic brain injury, blast, trauma, and combat associations in the Florida 

National Guard. Arch Phys Med Rehabil. 2012;93(11):1887-1895. 

Walker WC, Seel RT, Curtiss G, Warden DL. Headache after moderate and severe traumatic 

brain injury: a longitudinal analysis. Arch Phys Med Rehabil. 2005;86(9):1793-1800. 

Weaver LK, Wilson SH, Lindblad AS, et al. Hyperbaric oxygen for post-concussive symptoms 

in United States military service members: a randomized clinical trial. Undersea Hyperb Med. 

2018;45(2):129-156. 

Williams KA, Lawson RM, Perurena OH, Coppin JD. Management of Chronic Migraine and 

Occipital Neuralgia in Post 9/11 Combat Veterans. Mil Med. 2019;184(7-8):e207-e211. 

Winter L, Moriarty H, Robinson K. Employment Status Among U.S. Military Veterans with

Traumatic Brain Injury: Mediation Analyses and the Goal of Tertiary Prevention. Front Neurol. 

2019;10:190. 

Winter L, Moriarty HJ, Robinson K, et al. Efficacy and acceptability of a home-based, familyinclusive intervention for veterans with TBI: A randomized controlled trial. Brain Inj. 

2016;30(4):373-387. 

Wojtowicz M, Silverberg ND, Bui E, Zafonte R, Simon N, Iverson GL. Psychiatric 

Comorbidity and Psychosocial Problems Among Treatment-Seeking Veterans with a History o

Wolf G, Cifu D, Baugh L, Carne W, Profenna L. The effect of hyperbaric oxygen on symptoms 

after mild traumatic brain injury. J Neurotrauma. 2012;29(17):2606-2612. 

No outcome of interest

Aase DM, Babione JM, Proescher E, et al. Impact of PTSD on post-concussive symptoms, 

neuropsychological functioning, and pain in post-9/11 veterans with mild traumatic brain 

injury. Psychiatry Research. 2018;268:460-466. 

Armed Forces Health Surveillance C. Incident diagnoses of common symptoms ("sequelae") 

following traumatic brain injury, active component, U.S. Armed Forces, 2000-2012. MSMR. 

2013;20(6):9-13. 

Betthauser LM, Brenner LA, Cole W, Scher AI, Schwab K, Ivins BJ. A Clinical EvidenceBased Approach to Examine the Effects of mTBI and PTSD Symptoms on ANAM 

Performance in Recently Deployed Active Duty Soldiers: Results from the Warrior Strong 

Study. J Head Trauma Rehabil. 2018;33(2):91-100. 
Chronic Pain and mTBI Evidence Synthesis Program

108

Cook AJ, Meyer EC, Evans LD, et al. Chronic pain acceptance incrementally predicts disability 

in polytrauma-exposed veterans at baseline and 1-year follow-up. Behav Res Ther. 2015;73:25-

32. 

Cooper DB, Chau PM, Armistead-Jehle P, et al. Relationship between mechanism of injury and 

neurocognitive functioning in OEF/OIF service members with mild traumatic brain injuries. 

Mil Med. 2012;177(10):1157-1160. 

Finkel AG, Ivins BJ, Yerry JA, Klaric JS, Scher A, Sammy Choi Y. Which Matters More? A 

Retrospective Cohort Study of Headache Characteristics and Diagnosis Type in Soldiers with 

mTBI/Concussion. Headache. 2017;57(5):719-728. 

Finkel AG, Klaric JS, Yerry JA, Choi YS. Staying in service with posttraumatic headache: A 

retrospective cohort study of patient outcome. Neurology. 2017;89(11):1186-1194. 

Finkel AG, Yerry J, Scher A, Choi YS. Headaches in soldiers with mild traumatic brain injury: 

findings and phenomenologic descriptions. Headache. 2012;52(6):957-965. 

Kanefsky R, Motamedi V, Mithani S, Mysliwiec V, Gill JM, Pattinson CL. Mild traumatic 

brain injuries with loss of consciousness are associated with increased inflammation and pain in 

military personnel. Psychiatry Research. 2019;279:34-39. 

Klaric JS, Forbes LL, Finkel AG. Painful Craniofacial/Cervical Surface Area and Continuous 

Headache After Military Concussion: A Morphometric Retrospective Cohort Study. Headache. 

2018;58(9):1457-1464. 

Kozminski M. Combat-related posttraumatic headache: diagnosis, mechanisms of injury, and 

challenges to treatment. J Am Osteopath Assoc. 2010;110(9):514-519. 

Lindquist LK, Love HC, Elbogen EB. Traumatic Brain Injury in Iraq and Afghanistan 

Veterans: New Results from a National Random Sample Study. J Neuropsychiatry Clin 

Neurosci. 2017;29(3):254-259. 

Mac Donald CL, Johnson AM, Wierzechowski L, et al. Prospectively assessed clinical 

outcomes in concussive blast vs nonblast traumatic brain injury among evacuated US military 

personnel. JAMA Neurol. 2014;71(8):994-1002. 

Merritt VC, Jurick SM, Crocker LD, et al. Associations Between Multiple Remote Mild TBIs 

and Objective Neuropsychological Functioning and Subjective Symptoms in Combat-Exposed 

Veterans. Arch Clin Neuropsychol. 2020;02:02. 

Romesser J, Shen S, Reblin M, et al. A preliminary study of the effect of a diagnosis of 

concussion on PTSD symptoms and other psychiatric variables at the time of treatment seeking 

among veterans. Mil Med. 2011;176(3):246-252. 

Seidl JN, Pastorek NJ, Lillie R, et al. Factors related to satisfaction with life in veterans with 

mild traumatic brain injury. Rehabil Psychol. 2015;60(4):335-343. 
Chronic Pain and mTBI Evidence Synthesis Program

109

Song K, Wang CP, McGeary DD, et al. Five-year Pain Intensity and Treatment Trajectories of 

Post-9/11 Veterans with Mild Traumatic Brain Injury. J Pain. 2020;22:22. 

Stewart-Willis JJ, Heyanka D, Proctor-Weber Z, England H, Bruhns M. Premorbid IQ Predicts 

Postconcussive Symptoms in OEF/OIF/OND Veterans with mTBI. Arch Clin Neuropsychol. 

2018;33(2):206-215. 

Stojanovic MP, Fonda J, Fortier CB, et al. Influence of Mild Traumatic Brain Injury (TBI) and 

Posttraumatic Stress Disorder (PTSD) on Pain Intensity Levels in OEF/OIF/OND Veterans. 

Pain Med. 2016;17(11):2017-2025. 

Stratton KJ, Hawn SE, Amstadter AB, Cifu DX, Walker WC. Correlates of pain symptoms 

among Iraq and Afghanistan military personnel following combat-related blast exposure. J 

Rehabil Res Dev. 2014;51(8):1189-1202. 

Swan AA, Amuan ME, Morissette SB, et al. Long-term physical and mental health outcomes 

associated with traumatic brain injury severity in post-9/11 veterans: A retrospective cohort 

study. Brain Inj. 2018;32(13-14):1637-1650. 

Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning from 

Iraq or Afghanistan. Headache. 2010;50(8):1262-1272. 

Walker WC, Franke LM, Sima AP, Cifu DX. Symptom Trajectories After Military Blast 

Exposure and the Influence of Mild Traumatic Brain Injury. J Head Trauma Rehabil. 

2017;32(3):E16-E26. 

Walker WC, Nowak KJ, Kenney K, et al. Is balance performance reduced after mild traumatic 

brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multicentre study. Brain Inj. 2018;32(10):1156-1168. 

Wu E, Graham DP. Association of Chronic Pain and Community Integration of Returning 

Veterans with and Without Traumatic Brain Injury. J Head Trauma Rehabil. 2016;31(1):E1-12. 

Excluded study design

Baker VB, Eliasen KM, Hack NK. Lifestyle modifications as therapy for medication refractory 

post-traumatic headache (PTHA) in the military population of Okinawa. J Headache Pain. 

2018;19(1):113. 

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma 

in US soldiers: an observational study. Headache. 2011;51(6):932-944. 

Hoot MR, Khokhar B, Walker WC. Self-report Pain Scale Reliability in Veterans and Service 

Members with Traumatic Brain Injuries Undergoing Inpatient Rehabilitation. Mil Med. 

2019;09:09. 
Chronic Pain and mTBI Evidence Synthesis Program

110

Janak JC, Cooper DB, Bowles AO, et al. Completion of Multidisciplinary Treatment for 

Persistent Postconcussive Symptoms Is Associated with Reduced Symptom Burden. J Head 

Trauma Rehabil. 2017;32(1):1-15. 

Leung A, Fallah A, Shukla S, et al. rTMS in Alleviating Mild TBI Related Headaches--A Case 

Series. Pain physician. 2016;19(2):E347-E354. 

Ruff RL, Riechers RG, 2nd, Wang XF, Piero T, Ruff SS. For veterans with mild traumatic 

brain injury, improved posttraumatic stress disorder severity and sleep correlated with 

symptomatic improvement. J Rehabil Res Dev. 2012;49(9):1305-1320. 

Ruff RL, Ruff SS, Wang XF. Improving sleep: initial headache treatment in OIF/OEF veterans 

with blast-induced mild traumatic brain injury. J Rehabil Res Dev. 2009;46(9):1071-1084. 

Yerry JA, Kuehn D, Finkel AG. Onabotulinum Toxin A for the Treatment of Headache in 

Service Members with a History of Mild Traumatic Brain Injury: A Cohort Study. Headache: 

The Journal of Head & Face Pain. 2015;55(3):395-406. 

Duplicate publication of included study

Ferdosi H, Schwab KA, Metti A, et al. Trajectory of Postconcussive Symptoms 12 Months 

After Deployment in Soldiers with and Without Mild Traumatic Brain Injury: Warrior Strong 

Study. Am J Epidemiol. 2019;188(1):77-86. 

Lippa SM, Fonda JR, Fortier CB, et al. Deployment-related psychiatric and behavioral 

conditions and their association with functional disability in OEF/OIF/OND veterans. J Trauma 

Stress. 2015;28(1):25-33.
Chronic Pain and mTBI Evidence Synthesis Program

111

APPENDIX E. PEER REVIEW COMMENTS/AUTHOR

RESPONSES 

Reviewer 

Number Comment Author Response

Are the objectives, scope, and methods for this review clearly described?

1 Yes 

2 Yes

3 Yes

4 Yes

5 Yes

6 Yes

7 Yes

8 Yes

9 Yes

10 Yes

Is there any indication of bias in our synthesis of the evidence?

1 No

2 No

3 No

4 No

5 No

6 No

7 Yes - This review had tremendous amount 

rejection of articles. Would like to see a list of 

articles that were rejected by a third reviewer, 

as opposed to those that had 2 reviewers that 

agreed.

We understand this point. Our search 

terms were purposely broad to identify all 

possible papers with data on TBI and pain. 

This resulted in a large number of irrelevant 

studies that were excluded upon review of 

abstracts or full text for reasons such as 

focusing on moderate/severe rather than 

mild TBI, or being conducted in civilian 

samples (i.e., outside of the scope of this 

review). Inclusion/exclusion determinations 

were based on dual review and consensus. 

We now include a table of studies that were 

excluded after the full text review

(Appendix D).

8 No 

9 No

10 No

Are there any published or unpublished studies that we may have overlooked?

1 No

2 No

3 Yes - For awareness and potential mentionstudy of VHA cohort just published: Amy L. 

Byers, Yixia Li, Deborah E. Barnes, Karen H. 

Seal, W. John Boscardin & Kristine Yaffe

(2020) A national study of TBI and risk of 

suicide and unintended death by overdose and 

Thank you. We have cited this new 

publication in the Introduction and 

Discussion sections of the report.
Chronic Pain and mTBI Evidence Synthesis Program

112

firearms, Brain Injury, 34:3, 328-334, DOI: 

10.1080/02699052.2019.1701708

4 No 

5 No

6 No

7 No

8 No

9 No

10 No

Additional suggestions or comments can be provided below. If applicable, please indicate the page and 

line numbers from the draft report

1 This is a well-conducted and well-described 

review. I have only a few minor suggestions.

We appreciate the feedback.

Page 16: The authors have been appropriately 

inclusive in their selection criteria for studies of 

chronic pain and have not applied a strict 

definition of chronic pain; however, I think it 

would be helpful to provide a standard 

definition of chronic pain (e.g., IASP, National 

Pain Strategy) in the introduction.

Thank you for this suggestion. We have 

added a definition of chronic pain to the 

Introduction section of the report.

Page 58, lines 23-34: I think it is misleading to 

describe use of ICD-9/10 codes as 

“comprehensive diagnostic assessment.” ICD9/10 do not include a systematic approach to 

chronic pain, so studies using these codes 

typically infer the presence of chronic pain from 

codes that indicate the presence of a symptom 

(e.g., low back pain), imaging finding (e.g., disc 

degeneration), or disease (e.g., osteoarthritis) 

that may or may not be associated with chronic 

pain. Perhaps the best way to think about most 

of these codes is as “diagnoses potentially 

related to chronic pain.” Clinicians often do not 

code comprehensively, but typically chose 

codes for reasons related to billing. This could 

lead to under or over coding. In most cases 

when chronic pain is present, clinicians have 

little incentive to add codes for pain-related 

diagnoses because they add little to the overall 

complexity of the visit. In some cases, such as 

when patients have a service-connected 

condition potentially related to chronic pain, 

clinicians may code a pain-related diagnosis to 

spare a patient a copay, even if the condition 

was briefly discussed and determined not to be 

bothersome.

Thank you for this information. We agree 

that ICD diagnosis codes do not 

necessarily equate to chronic pain and 

there are circumstances when the use of 

these codes may increase false positive or 

false negative rates. We have edited the 

report to include this as a limitation to the 

conclusions drawn from studies using ICD 

codes. Additionally, we have reviewed and 

edited the report for use of appropriate 

language, including the suggested 

“diagnoses potentially related to chronic 

pain.”

2 This reviewer appreciates the efforts put forth 

to produce this review. Methods are clearly 

articulated and implemented.

We appreciate this feedback.

*May be helpful to clarify that the most robust 

study - Key Question 1 - CTBIE - findings - are 

for that specific cohort. The fact that those in 

this group also had the most comprehensive 

We agree. We have added additional 

information about the CTBIE to the Results 

section, including potential caveats when 

interpreting findings from these studies. 
Chronic Pain and mTBI Evidence Synthesis Program

113

eval creates further challenges in terms of 

interpretation. 

*The role of co-occurring MH sx could be 

further integrated throughout. If this is not 

possible - may be helpful to identify as a 

limitation.

Though this was outside the scope of Key 

Question 1, Key Question 2 examined 

suicide-related outcomes (evidence from 1 

study). Key Question 3 examined whether 

benefits or harms of treatment differed by 

mental health comorbidities, though due to 

the small number of studies and 

participants relevant to this key question, 

we were unable to generalize about 

potential impacts of mental health 

comorbidities. We have noted this as a 

limitation of our review and recommended 

it as a future research area in the 

discussion. We have also included a 

discussion section highlighting differences 

in prevalence estimates for individuals with 

PTSD: “Although we did not find strong 

evidence suggesting that pain prevalence 

varied by mTBI etiology, it was clear across 

studies that, when examined, pain 

prevalence levels were substantially higher 

among those with comorbid PTSD. 

Although the assessment of pain 

prevalence by comorbid PTSD was not a 

specified focus of KQ1, the consistency of 

this finding across studies is noteworthy, 

particularly given the high prevalence of 

diagnoses PTSD among those with a 

history of mTBI. This finding lends further 

evidence to prior discourse about the 

“polytrauma clinical triad”25 and has 

implications for the ongoing clinical 

management of Veterans and SMs with 

mTBI.”

*In addition, further discussion of multiple pain 

types and clinical implications would be useful.

We have included a description of pain 

definitions in the evidence tables to 

facilitate comparisons across different 

definitions of pain used in the included 

studies. Few studies reported the 

prevalence of participants with multiple 

pain types; however, where possible, we 

have added this information to the Results 

section as well as a description of the 

clinical implications in the Discussion 

section.

3 1. P4 (line 46) Consider reporting the higher 

rates of suicide in Veterans with history of 

mTBI (beyond non-TBI or all Veterans). Given 

that suicide is VA's clinician priority, it may be 

prudent to briefly summarize findings from 

published, peer-reviewed studies on the 

prevalence of suicide following TBI. This may 

serve to highlight it's importance for this 

We have added text and references to the 

Executive Summary identifying the higher 

rates of mortality, and suicide mortality, 

among Veterans with a history of mTBI. In 

the full Introduction section, we have added 

a paragraph describing the findings from 

past peer-reviewed studies.
Chronic Pain and mTBI Evidence Synthesis Program

114

population in light of the lack of studies that 

met the ESR's criteria.

2. The ESR on mTBI and pain could be 

stronger by mentioning the contributions of 

other factors, including prevalent 

medical/mental health comorbidities to 

pain/symptom chronicity. Along the same lines, 

the conclusion could be more compelling from 

a clinical, research and VHA policy perspective 

if there was brief mention of the impact of coexisting mTBI and pain on (for example) longterm healthcare utilization, functional outcomes 

and quality of life.

We agree with this recommendation and 

have added more information on the 

consideration of comorbidities in the 

included studies and the potential interplay 

of comorbidities with chronic pain among 

those with mTBI. Similarly, we have 

included a brief reference to likely 

healthcare utilization, functional outcomes, 

and quality of life in this patient population. 

Very interesting to read and informative ESR. 

Thank you.

We appreciate this feedback.

4 This is a very nice review and summary of the 

literature. I appreciate the authors grouping of 

the studies and the fact that the summary 

results were not overstated. I would like to 

recommend a paragraph in the executive 

summary that provides a high level overview of 

the noted gaps in the literature as this would be 

helpful for future grant applications to 

reference. There body of the report could 

include a short discussion of the gaps in the 

literature and challenges (lack of consistent 

use of similar outcome measures, impact of comorbid MH diagnosis and pain prevalence 

which is already described on page 64, 

recommendations to include suicide risk 

assessment in future studies, and need for 

treatment studies).

Overall very nicely done.

Thank you for this suggestion. We have 

added a paragraph to the executive 

summary identifying the gaps and 

challenges and have now better highlighted 

this throughout the report, including 

additional text in the Discussion section.

5 P 2 line 49 figure 2 Insert comment/analytics 

about the reasons for the wide range of 

reported prevalence's and how this affects 

report utility.

We have added text describing the likely 

reasons for heterogeneity in prevalence 

estimates as well as the effect on report 

utility.

6 As expected, this is a critical, comprehensive, 

unbiased, and important review of the scientific 

literature regarding co-occurring TBI and pain 

that identifies both the limited available high 

quality literature and the lack of clinically 

important associations. I have no significant 

recommended edits or additions.

Thank you. We agree this review highlights 

gaps in the current literature and important 

next-steps for addressing chronic pain 

among Veteran and military populations 

with a history of mTBI.

7 Would like a list of publications that required a 

tie-breaker vote.

We now include an appendix (Appendix D) 

with the list of studies excluded after full 

text review. We used dual review and team 

consensus to determine study eligibility.

8 This Evidence Synthesis Program review is 

both timely and significant in light of growing 

attention to chronic pain as a significant public 

health and clinical problem, particularly for 

Veterans and Military Service Members (SMs). 

We appreciate this feedback.
Chronic Pain and mTBI Evidence Synthesis Program

115

Overall, the report is very well done. 

Prespecified key questions were addressed 

appropriately via strong and well-supported 

review and thoughtful and comprehensive 

discussion of the findings. Although there are 

numerous concerns about the reliability and 

reproducibility of the findings, the authors have 

generally acknowledged serious limitations of 

the existing literature and the approach to 

answering the questions. The methods 

employed in the search process are state-ofthe-art and encourage confidence that the 

literature relevant to addressing key questions 

was identified and considered. 

The description of individual studies identified 

in the search is a strength of the report. Tables 

are particularly valuable in capturing key 

features of individual studies. While the 

authors’ efforts to draw conclusions based on a 

summary of these findings given the 

heterogeneity of the studies and their 

approaches is admirable, summary statements 

and conclusions based on this review are likely 

to be less than optimally useful in informing 

operational partner interests in identifying 

actionable recommendations for improving the 

care of Veterans and SMs with co-occurring 

mTBI and chronic pain.

Numerous concerns and recommendations for 

improving the quality of the report, most of 

which already acknowledged by the authors, 

can be cited.

In the Executive Summary, care is taken to 

explicate how “chronic pain” was ascertained. 

However, the examples don’t provide 

confidence since standard definitions of 

chronic pain abound, and none would consider 

pain lasting 30 days as “chronic.” I think that 

inclusion of studies that explicitly including 

persons with pain for only the past month is a 

mistake. Surely, most people experiencing a 

significant TBI will experience acute head pain, 

and since TBI in this population commonly is 

associated with polytrauma, that is, injury to 

other sites, as well, acute pain may occur in 

sites other than the head and face, as well. 

Multiple other caveats should be noted, even in 

the Executive Summary. For example, arthritis 

can be painful, but for many who have a 

diagnoses of osteoarthritis, for example, pain 

may be rare (people with the disease can go 

long periods without any pain, and even then, 

We agree that there are limitations related 

to broadly defining chronic pain in this 

manner. Though we include more studies, 

it is not as clear that all participants met a 

more conservative definition of chronic pain 

when the definitions are allowed to vary so 

greatly. We have attempted to mitigate this 

concern by providing definitions of chronic 

pain used in each of the primary studies in 

the evidence tables. We can also assume 

that in many cases, when a participant 

responds that they have had pain for at 

least 30 days, that the pain lasted longer 

than that period of time in many cases (i.e., 

many positive endorsements of this item 

likely indicate chronic pain, though some 

cases might possibly reference acute pain 

lasting just over 30 days). This is 

particularly likely because many pain 

assessments were reflective of routine 

follow-up assessment of pain, not 

assessments completed at the time of 

injury (i.e., one can assume that the pain 

lasted longer than 30 days). Other 

assumptions such as that a diagnosis of 

osteoarthritis is associated with chronic 
Chronic Pain and mTBI Evidence Synthesis Program

116

most “flares” are short in duration) and it can 

certainly not be assumed that people with a 

diagnosis of arthritis experience chronic pain. 

Also, the currently accepted nomenclature 

increasing distinguishes “chronic pain” and 

“high impact chronic pain.” A note about this 

potentially important distinction would be 

helpful.

pain are well supported in the literature, 

though our description of the chronic pain 

measures and definitions in each included 

study enables readers to select and 

examine only those with a more narrow 

and specific definition if they so choose.

Finally, we mention the distinction between 

chronic pain and high impact chronic pain 

in the revised discussion section, though 

note that most included studies were 

published prior to this terminology being 

commonly used.

Realizing that many studies reported on 

prevalence of headache or migraine as a 

single group, I’m not sure of the value of this 

approach given that migraine is understood to 

be a specific condition that is quite distinct from 

other headache conditions. In the context of 

mTBI, this difference may be particularly 

important.

We agree that these are distinct conditions 

and have now made edits throughout the 

report to help distinguish these two types of 

pain conditions. We have reported data for 

headache and migraine prevalence 

separately when the distinct data were 

reported separately in the primary studies. 

Of the 23 included studies for Key Question 

1, only 1 combined headaches and 

migraines; 4 reported both outcomes 

separately, and the remaining 18 reported 

only headaches with no mention of 

migraines. 

Also, as important is the definition used to 

define mTBI, so I think this should be added. 

This is not a minor point, since it could have 

been expected that an answer to key questions 

hinges on the operational definition of both 

mTBI and chronic pain that is applied in the 

search.

We agree and have added a standard 

definition of mTBI to the report. We chose 

to include studies with a range of 

approaches for operationalizing “mTBI” in 

order to include all available and relevant 

data for the Key Questions of interest. 

Though this means that some studies were 

included that may have used a broader 

definition of mTBI than that we cited, we 

have described these approaches in the 

evidence tables and considered the 

definitions and operationalizations in the 

data synthesis. Readers who are interested 

in a more specific definition or 

operationalization of “mTBI” can utilize the 

evidence tables to examine only the 

studies using definitions relevant to their 

questions of interest.

Bottom of page 1 (page 9/94) - Reference to 

“pain medication” includes “non-analgesics” as 

example; it is unclear what is meant by a nonanalgesic pain medication. The authors 

probably intended to refer to “non-opioids” 

such as NSAIDS and/or “co-analgesics” such 

or anti-depressants or gabapentinoids.” This is 

not a minor point, since many medications 

have analgesic properties and are commonly 

used for purposes other than pain 

management (even NSAIDs).

We appreciate this point. The original 

publication provides no additional detail 

about this category of data and the two 

publications that reported data from the 

same parent study did not include a 

category with this label. We have therefore 

removed “non-analgesic pain medication” 

from the findings section of the report.
Chronic Pain and mTBI Evidence Synthesis Program

117

Be more careful in use of terms such as 

“directly related to mTBI.” (Page 2) How is this 

term defined? For example, does it mean that 

the onset was at the same time? Or that there 

was evidence of trauma to the specific site? 

Although one might conclude that “headache” 

could be associated with TBI, that’s not 

necessarily the case, since headache is known 

to be common in younger persons including an 

unknown proportion of SMs prior to their 

military service. And, of course, TBI is often 

associated with traumatic injury to other body 

sites, including painful traumatic injuries. Or 

pain may emerge in the context of prolonged 

bed rest and/or activity restrictions and other 

factors, even other treatments, in the context of 

acute treatment for TBI.

Thank you for bringing this to our attention. 

We have revised the language in the report 

to better represent the variety of 

circumstances in which individuals with 

mTBI may experience chronic pain (and, in 

most cases, our inability to distinguish 

between them).

I’m not sure how valuable Figure ii is. It seems 

likely that there are many factors that affect 

prevalence estimates of chronic pain across 

studies reporting on specific sites, so it doesn’t 

seem helpful to know how estimates vary 

within pain site and to try to compare them 

across sites, as implied by presenting the 

estimates in a single figure.

We have included Figure ii to summarize 

findings from Key Question 1 and not 

necessarily to compare prevalence levels

across pain conditions. We have retained 

this Figure because we believe it helps 

depict the state of the science on pain 

condition prevalence in Veterans and 

Servicemembers with mTBI. 

The first sentence on page 3 should be 

referenced and information about the 

methodology, and a critique of the weaknesses 

of the study, should be provided. The CTBIE 

should be described. Is it a clinical exam or 

self-report measure?

Thank you. We have added a citation to 

this sentence and provided more context 

about the study, including the CTBIE.

I note that later in the Summary, a point is 

made that this measure is completed by 

treatment-seeking patients. Of course, this fact 

suggests that the estimates of prevalence of 

chronic pain in such samples will be highly 

inflated (if one is interested in true population 

level estimates). The following sentence about 

an observational study using VA health record 

data seems at least as relevant; I’m not sure 

why the estimates reported in this study are 

questioned whereas the estimates from the 

former “best” study are not.

We concur that estimates will be greatly 

influenced based on whether participants 

are seeking treatment or part of a general, 

non-treatment seeking sample. We have 

edited this section to provide better 

consistency in our evaluation of study 

samples. Additionally, we have included 

this consideration in our risk of bias 

assessment of the included studies and 

provided detailed information regarding the 

samples and inclusion criteria to 

transparently provide readers with 

information pertaining to potential sources 

of bias.

On page 3, the term “pain interference” is 

introduced and should be defined. How was 

‘moderate to severe pain” defined? Note that 

the concept of having pain on half the days in a 

specific time frame is an accepted way to 

operationalize “chronic pain” although a 

minimum three-month period (or six-month) is 

usually required.

Thank you. We have now defined “pain 

interference” as well as pain severity levels.

Again, headache and migraine should not be 

considered as a single “pain type.” They are 

As noted above, we have now been more 

careful to distinguish between these two 
Chronic Pain and mTBI Evidence Synthesis Program

118

quite distinct and should not be considered 

together. Also, note that these diagnoses are 

known to be poorly identified by clinicians and 

particularly poorly captured in the electronic 

record.

distinct conditions in the report. We 

reported prevalence data for the conditions 

separately when the data were reported 

separately in the primary studies. Of the 23 

included studies for Key Question 1, only 

one combined headaches and migraines; 4 

reported both outcomes separately, and 

the remaining 18 reported only headaches 

with no mention of migraines.

The paragraph beginning with “Five studies” on 

page 3 is not useful without explication of how 

medication use was employed to define 

presence of chronic pain.

Thank you. We have clarified this 

paragraph and revised other locations in 

the report where pain medication use is 

used as a proxy measure for chronic pain.

With regard to KQ1b, etiology is apparently 

solely defined in terms of history of blast-injury 

and LOC. Another important factor studied in 

the literature is whether pain is at the site of 

traumatic injury, so since TBI often occurs in 

the context of multiple sites of injury, and since 

sites of pain other than the face or head are 

being examined, then whether the onset of 

pain co-occurred with the mTBI may also be 

important.

This is an interesting point and one that we 

would like to include in the report. 

However, the included studies do not report

details on polytraumatic sites of injury or 

timing of pain onset. We have included this 

point as a potential limitation of the review 

findings and a gap in the current literature.

With regard to KQ1c, the issue of pain 

measurement is critical. As already noted, 

inferring the presence of chronic pain from ICD 

or medication use data is fraught with 

problems. In addition, the population from 

which study samples were derived is also a 

critical variable. Prevalence estimates from 

samples of treatment seeking persons will 

clearly result in inflated estimates. And 

although some ICD codes specifically include 

the word “chronic” in the name of the 

diagnosis, most potentially painful conditions 

do not. The report from Goulet et al., 2016 

noted that a large proportion of Veterans with 

musculoskeletal diagnoses such as 

osteoarthritis reported no pain on the date of 

the diagnosis. Even more problematic is 

inferring the presence of chronic pain from 

health record data on medication fills. Greater 

clarity in the description of the approaches 

employed both in the studies and during the 

review is important to encourage confidence in 

the results of the review.

We agree with the reviewer on each of 

these assessments. Per our prior 

responses, we have added text to the 

report to clarify the pain assessment 

methods used in each of the studies and to 

acknowledge the limitations inherent to 

these methods. We have also now cited 

the Goulet et al. 2016 paper in the 

Discussion section of the report. 

The bottom line is that the detailed reporting of 

the prevalence rates reported in the literature is 

not particularly relevant given all the apparent 

differences in the methods across studies from 

which these estimates were derived. It seems 

to me that it would be more important to 

summarize the variations and limitations of the 

literature rather than presenting estimates that 

are almost certainly unreliable and not 

We understand this recommendation. In 

the revised report, we have taken care to 

specify the variations and limitations of the 

literature and to not make inferences based 

on disparate study types. Additionally, the 

referenced conclusion statement has now 

been moved to an earlier section of the 

Executive Summary to help highlight this 

point.
Chronic Pain and mTBI Evidence Synthesis Program

119

meaningful. The conclusion in the paragraph 

on the top of page 4 should be moved to the 

front of the summary.

Although I was a member of the Technical 

Expert Panel that helped develop the key 

questions and approach, in retrospect, it 

seems that the review was likely misguided. 

Rates of chronic pain are known to be high 

among Veterans and SMs. A CDC MMWR 

published in 2017 reported that Veteran status 

was specifically and uniquely associated with 

the presence of chronic pain. Other data on 

Veterans and SMs also encourage similar 

conclusions. The key question is not whether 

prevalence rates are high among Veterans and 

SMs with histories of mTBI, it’s whether the 

rates of chronic pain are higher in this 

subpopulation than among the general 

population of Veterans and SMs.

We agree with this sentiment. Although the 

Key Questions and approach remain the 

same, we have taken this opportunity to 

revise the results section for Key Question 

1 so that, where available, prevalence 

estimates of chronic pain are included for 

those with, versus without, a history of 

mTBI. We have also added a summary of 

these findings to the Executive Summary 

and to the Discussion section.

Similarly, KQ3 might have been more 

appropriately specified as whether there is 

evidence that Veterans and SMs with mTBI are 

less likely to accrue benefit from commonly 

delivered interventions for chronic pain. In the 

absence of answers to these questions, it 

seems that current policies for universal 

screening for the presence and intensity of 

pain, and for suicide risk assessment, should 

continue, and that Veterans and SMs with 

histories of mTBI should continue to be offered 

evidence-based treatments for chronic pain.

Thank you for this feedback. We have 

added additional information about this 

important consideration to the discussion of 

Key Question 3.

9 Line 17 P1: Helpful to include databases 

searched in the summary as described on P10 

Search Strategy.

Thank you. This has been added to the 

summary.

Huge variability in the incidence of headaches -

3 - 98%. What could this be attributed to?

We agree. The wide range is likely due to 

variation in study design, particularly in 

samples, pain definitions, and pain 

ascertainment periods. This has been 

added to the report.

It is extremely interesting that the analysis 

started with >2000 pubs but only 31 made the 

"cut". Are your inclusion/exclusion criteria too 

stringent? Can you use some of the studies or 

parts of studies not meeting criteria? There is a 

paucity of studies in the area and most of these 

studies are of poor quality.

Our search terms were purposely broad to 

identify all possible papers with data on 

mTBI and pain. This resulted in a large 

number that were excluded upon review of 

abstracts or full text. Inclusion and 

exclusion determinations were based on 

dual review and consensus. We now 

include an appendix (Appendix D) table of 

studies that were excluded after the full text 

review.

10 Page 25 line 22-23 has an incomplete 

sentence.

Thank you. We have edited this sentence.

Table 2: Reference 4 also provided prevalence 

of "other pain". This is other musculoskeletal 

pain including arthritis. If the mixed definition is 

We agree and have added the data from 

this reference to the “other pain” section. 
Chronic Pain and mTBI Evidence Synthesis Program

120

the reason for exclusion of this, that makes 

sense. If the authors think this should be 

included it could be added to the other pain 

aspect of Table 5

For the study examining suicide, it may be 

worthwhile to also note that the phenotype that 

transitioned from relatively healthy to 

Polytrauma phenotype where chronic pain 

emerged between year 1 and 5 also had 

significantly higher odds of suicidal 

ideation/attempt after the phenotype 

development period.

Thank you. We have added the Moderately 

Healthy + Decline phenotype to these 

findings.