Surgical Treatment of Post-surgical Mastectomy Pain Utilizing the Regenerative Peripheral Nerve Interface (RPNI)
Phase: NA
Conditions: Post-Mastectomy Chronic Pain Syndrome
Sponsor: University of Michigan Rogel Cancer Center

ID: UMCC 2018.124    
Surgical Treatment of Post-surgical Mastectomy Pain Utilizing the Regenerative Peripheral Nerve Interface 
NCT04530526

version 9.0 
11.20.19 
 
Surgical treatment of post-surgical mastectomy pain utilizing the 
regenerative peripheral nerve interface (RPNI) 

version 9.0 
11.20.19 
 
PROTOCOL SUMMARY 
 
Title: 
Surgical treatment of post-surgical mastectomy pain utilizing 
the regenerative peripheral nerve interface (RPNI) 
 
Summary: 
Up to 40% of patients who undergo mastectomy suffer from chronic 
pain, defined as pain lasting greater than three months. Chronic 
post-mastectomy pain due to nerve injury leads to long-term opioid 
use and diminished quality-of-life. A novel surgical approach to 
neuroma treatment, the regenerative peripheral nerve interface 
(RPNI) developed to treat painful neuromas associated with limb 
amputation has shown significant reductions in patient-reported pain. 
RPNI surgery is now available through Michigan Medicine’s Multi- 
Disciplinary Peripheral Nerve (MDPN) Clinic to improve post- 
mastectomy pain and definitively treat intercostal neuromas following 
mastectomy. Using patient-reported outcomes and clinical data we 
will evaluate the use of RPNI surgery to reduce persistent post- 
mastectomy pain in women seeking surgical consultation through the 
Plastic Surgery or MDPN clinics. 
 
Objectives: 
Our central hypothesis is that intercostal nerve RPNI surgery 
significantly reduces chronic post-mastectomy pain without 
neuroma recurrence. We will employ an observational study design 
with patients serving as their own controls prior to surgery to assess 
pain levels before and after RPNI surgery for intercostal neuroma. 
 
Population: 
Adult female patients (18 years old) presenting to Michigan 
Medicine’s MDPN Clinic with post-mastectomy pain persisting at 
least six months removed from mastectomy will be eligible for 
participation. 
 
Number of Sites: 
Single Center - University of Michigan 
 
Study Duration: 
Two years (NIH funded). Three years total. 
 
Subject Participation 
Duration: 
Approx. 12 months. 
 
Description of Intervention: 
Survey based patient reported outcomes from patients undergoing 
RPNI surgery, clinical data collection 
 
Enrollment Period: 
12 months 
 
Estimated Sample Size: 
25 patients 

3 
 
 
1. KEY ROLES 
 
Individuals: 
Principal Investigator: 
 
David Brown, MD. Michigan Medicine Plastic Surgery 
 
Co-Investigators: 
 
Theodore Kung, MD. Michigan Medicine Plastic Surgery 
 
Sean Smith, MD. Michigan Medicine Physical Medicine and 
Rehabilitation 
 
Hyungjin Myra Kim, ScD. UM Center for Statistical Consulting 
and Research 
 
Shailesh Agarwal, MD, University of Chicago (consultant) 
 
Project Management: 
 
Jennifer B Hamill M.P.H., Michigan Medicine Plastic Surgery 
 
 
 
Institution: 
University of Michigan, Section of Plastic Surgery 
2130 Taubman Center 
1500 E. Medical Center Dr. 
Ann Arbor MI 48109 
 
David Brown, MD 
Domino's Farm, Lobby A 
24 Frank Lloyd Wright Dr. Suite A1200 
Ann Arbor, MI 48105-9484 
Phone: 734-998-6022 
Fax: 734-998-6696 
E-mail: davbrown@med.umich.edu 
 
 
 
Funding Source: 
NCI Funded Clinical and Translational 
Exploratory/Developmental Study 

4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 1. Targeting intercostal neuromas with RPNIs for 
treatment of post-mastectomy pain followed by pain 
evaluation (Aim 1) and neuroma evaluation (Aim 2). 
2. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
2.1 
Background Information 
 
Up to 40% of patients who undergo mastectomy suffer from chronic pain, defined as pain lasting greater 
than three months. Even three years after surgery, nearly 25% of patients continue to report moderate 
pain (3, 4). However, mastectomy remains a mainstay of treatment for over 25% of breast cancer patients 
(5), necessitating novel, adequate solutions for the significant and debilitating issue of chronic pain. 
 
Previous studies have documented that breast cancer patients with post-surgical pain experience worse 
quality-of-life with respect to patient-reported physical well-being, physical autonomy, relationships, and 
psychological well-being (6, 7). Nearly 11% of opioid naïve patients who undergo breast cancer surgery 
continue to require opioids for pain relief at least three months after surgery, and the opioid dosing 
regimen for these patients approaches that used for chronic opioid users (8). Even 7-9 years after surgery, 
many breast cancer patients report requiring opioid medication for post-mastectomy pain (9). In addition to 
opioids, management of chronic post-mastectomy neuropathic pain consists of non-steroidal anti- 
inflammatory drugs (NSAIDs) and neuropathic medications including gabapentin or amitriptyline (11). 
However, these strategies are often insufficient due to adverse medication effects, incomplete pain relief, 
and poor patient compliance. 
 
Several reports have demonstrated that cutaneous nerve injury substantially contributes to post- 
mastectomy pain (12, 13). Altered sensation, including ‘pins and needles’ sensation and/or shock-like, 
burning, or stabbing pain in the known distribution of chest wall sensory nerves suggest a neuropathic 
etiology (14). A handful of small studies have documented the relationship between chronic post- 
mastectomy pain and injury to subcutaneous, sensory branches of the intercostal nerves in the chest (8, 
9). Identification of patients with a neuropathic component to their pain, and development of a strategy 
which addresses the underlying nerve injury would offer an opportunity to definitively treat chronic post- 
mastectomy pain. 
 
The regenerative peripheral nerve interface (RPNI) has 
emerged as a novel strategy to treat neuromas in peripheral 
nerves. The RPNI consists of the residual peripheral nerve end 
implanted in a skeletal muscle or skin graft, following surgical 
resection of the injured terminal nerve portion (neuroma) (Fig. 
1). The free muscle or skin graft is separated from its native 
nerve innervation, leaving open neuromuscular junctions for 
ingrowth and attachment of nerve fibers from the implanted 
nerve; animals studies show that this provides a physiologic 
end-organ for the implanted nerve without neuroma recurrence 
(1, 2, 15, 16). We have performed RPNIs to treat painful 
neuromas associated with limb amputation, with significant 
reductions in patient- reported pain (10). Recently, we have 
performed RPNIs to treat histologically-confirmed intercostal 
neuromas in patients with chronic post-mastectomy pain. 
 
Limited follow-up suggests that these patients experience 
substantial improvement in their pain, although formal evaluation is required. 

5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 3. Typical finding of intercostal 
neuroma showing mass of scar 
(yellow arrow) in continuity with 
intercostal nerve (green arrow) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 2. Nerve distribution of the 
chest wall and breast including 
contribution from intercostal 
nerves. (Adapted from 
Wijayasinghe et al 2014) 
2.2. Significance 
 
2.2.1. Mastectomy causes long-term pain. Over 25% of breast cancer patients undergo surgical 
management with mastectomy(5) and even more with partial mastectomy (lumpectomy). In these 
procedures, the breast tissue is removed from the chest wall, necessitating the transection of small 
sensory nerves present and traveling through these tissues (Fig 2). Reports indicate that up to 40% of 
patients who undergo mastectomy report pain lasting greater than three months; even three years after 
surgery, nearly 25% of patients continue to report moderate pain(4). Therefore, 
post-mastectomy pain affects a substantial number of patients even after 
completion of breast cancer management. 
 
2.2.2. Post-mastectomy pain causes substantial patient morbidity. Studies 
have demonstrated that patients with post-mastectomy pain experience 
significantly worse quality-of-life with respect to physical well-being, physical 
autonomy, relationships, and psychological well-being (7). Long-term pain 
contributes to decreased work-function, increased healthcare utilization, and 
increased depression risk (6). Therefore, post-mastectomy pain has far-reaching 
physical and psychological consequences for patients. 
 
2.2.3. Post-mastectomy pain leads to opioid dependence. Using a national 
data set of insurance claims, Lee et al showed that 11% (2,451 out of 22,379) of 
opioid naïve patients who underwent mastectomy continued to require opioids for 
pain relief at least three months after surgery (8). These patients often require 
opioid doses that approximate doses used by chronic opioid users, equivalent to six tablets of 5-mg 
hydrocodone per day (8). These effects are long-lasting, as even 7-9 years after surgery, mastectomy 
patients report requiring pain medication (9). 
 
2.2.4. Nerve injury contributes substantially to post-mastectomy pain. Several studies have 
demonstrated that sensory nerve injury provides a substantial contribution to post-mastectomy pain (12, 
13). This is not surprising given that multiple sensory nerves are at risk during mastectomy including the 
intercostobrachial nerve, pectoral nerves, and segmental intercostal nerves 
(Fig 2)(14); pain in these nerve distributions is characteristic of patients with 
post-mastectomy pain. Physical exam findings such as altered sensation 
including pins and needles sensation and/or shock-like, burning, or stabbing 
pain all provide diagnostic evidence of a painful neuroma caused by nerve 
injury. Histologically, we have found that neuromas at limb amputation sites 
demonstrate disorganized axonal growth, with excessive connective tissue and 
fibroblasts. We have observed gross anatomic findings consistent with 
intercostal neuroma including the presence of a mass of scar in continuity with 
nerve fiber (Fig 3); histologically these sites demonstrate findings consistent 
with neuroma as described above. These findings provide strong evidence that 
neuromas contribute to post-mastectomy pain. 
 
2.2.5. Current pharmacologic treatment strategies for symptomatic 
neuromas are insufficient. Current pharmacologic pain management 
strategies for symptomatic neuromas include opioids, non-steroidal anti- 
inflammatory drugs (NSAIDs), and neuropathic drugs including gabapentin or 
amitriptyline (11). However, these strategies are often insufficient due to 
incomplete pain relief, poor compliance, and adverse effects including chronic 
dependence (opioids), gastrointestinal distress (NSAIDs), and dizziness and fatigue (neuropathic drugs). 
Therefore, a definitive strategy to reduce pain associated with symptomatic neuromas is needed. 

6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 5. Healthy, innervated 
myofibers present in an 
RPNI upon histologic 
examination after several 
 
 
 
 
 
 
 
 
 
 
 
Fig 4. Schematic representation of RPNI procedure 
(left) and final RPNI appearance (right).(1) 
2.2.6. Emerging surgical treatment modalities for post-surgical neuropathic pain require 
improvement 
 
Multiple surgical techniques have been described for addressing neuroma pain (21-27); however, none are 
widely used because of poor reliability and frequent recurrence of neuroma symptoms. Currently, the most 
frequently performed surgical intervention for a symptomatic neuroma is to bury the end of the nerve into 
normal (innervated) local muscle tissue after excision of the end neuroma (23, 24). A critical limitation is 
that none of these techniques permit regenerating axons to form new neuromuscular junctions with muscle 
fibers, a physiologic phenomenon that precludes neuroma recurrence. Furthermore, these operations have 
only been sparingly reported for chest wall pain (28, 29). Therefore, a surgical strategy treating post- 
mastectomy pain deserves further investigation. 
 
2.3. Innovation 
 
2.3.1. Formation of a multidisciplinary peripheral nerve clinic which treats patients with post- 
mastectomy pain.  We now recognize the underappreciated 
association between intercostal sensory nerve injury and pain in 
mastectomy patients. To this end, we have formed an 
interdisciplinary treatment team, consisting of peripheral nerve 
surgeons, neurosurgeons, pain anesthesiologists, and physiatrists, 
who work together to consult on, diagnose, and treat patients with 
post-surgical neuropathic pain at our institution. This provides the 
environment to appropriately diagnose, monitor, and treat patients. 
This approach also allows for a standardized approach to patients, 
which facilitates our ability to study the response to specific 
interventions. 
 
2.3.2. Regenerative peripheral nerve interface (RPNI) for 
neuroma pain. 
 
The Regenerative Peripheral Nerve Interface (RPNI) is a novel strategy to treat pain caused by neuroma 
formation at the ends of transected peripheral nerves. Following resection of the neuroma, the residual 
proximal end of the nerve is implanted into a free skeletal muscle or skin graft (Fig 4). Extensive preclinical 
testing in animal models demonstrated the feasibility, longevity, and durability of the RPNI at amputation 
sites (1, 15, 16). Histologic analysis of RPNIs has revealed: 1) muscle fibers comprising the free muscle 
grafts robustly regenerate within several weeks after implantation (Fig 5), 2) the 
implanted peripheral nerve ends form new neuromuscular junctions within the free 
muscle grafts (Fig 6), and 3) no evidence of neuroma was detected within the 
RPNIs (2). That action potentials can be transduced through the RPNI from the 
nerve into the muscle graft provides additional evidence that regenerating axons 
reinnervate muscle fibers rather than forming neuroma (2, 30). These successes 
in a small animal model have led to RPNI in a non-human primate model. Multiple 
RPNIs were implanted into two rhesus macaque monkeys and extensive histologic 
and electrophysiological tests were successfully conducted for up to 20 months 
showing RPNI nerves re-innervated the muscle graft and did not form neuromas 
(1).  Similar studies utilizing dermal skin grafts, placed around the ends of sensory 
nerves, have shown similar endpoints.   
 
Briefly, a neuroma source of pain is confirmed upon detection of characteristic pain, 
combined with reproducible tenderness upon mechanical stimulation over the 

7 
 
Neuroma pain score 
Phantom pain score 
Pre-op 
Post-op 
Pre-op 
Post-op 
Fig 7. RPNI surgery improves neuroma pain 
score (p<0.0001) and phantom pain score 
(p<0.01) in amputation patients (10) 
location of the neuroma (Tinel sign). Confirmation of the 
neuroma as the source of pain can be accomplished with 
the use of ultrasound-guided nerve blocks. In the 
operating room, the symptomatic neuroma(s) are then 
easily identified at the amputation site; the neuroma is 
excised from the end of the peripheral nerve and RPNI is 
created by implanting the nerve end into a small free 
muscle or skin graft. A retrospective analysis of 16 
amputation 
patients who 
underwent 
RPNI surgery to 
treat 
symptomatic neuromas demonstrated the immense potential of 
this technique (10). A majority of patients in this study reported 
high satisfaction rates with RPNI surgery and neuroma pain 
scores were significantly lower post-operatively (Fig 7). To date, 
we have performed RPNI surgery in over 100 amputation 
patients and have data demonstrating safety and potential 
efficacy of RPNIs for these patients. 
 
Recently, we applied the RPNIs surgical model to patients with 
post-surgical chronic chest wall pain (Fig 8). Although evaluation of such patients is proposed in this study 
is ongoing, our limited follow-up at this time suggests that these patients have experienced a substantial 
improvement in their pain. The promising data generated from both animal studies and human patients 
support execution of a prospective pilot clinical trial to evaluate the effects of RPNI surgery on post- 
mastectomy patient-reported outcomes and durability of neuroma treatment. Upon completion of this 
proposal, we expect to have sufficient preliminary data to begin a multi-institutional clinical trial, leveraging 
our current collaboration with other institutions for the management 
of chronic pain in post breast-surgery patients (31). 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 8. Intraoperative image of intercostal RPNI 
surgery showing multiple intercostal nerves 
requiring RPNIs (yellow arrows) 
Fig 6. New neuromuscular junctions (NMJ) between muscle 
and free nerve end form in the RPNI (right); control image 
shows the appearance of NMJ in uninjured muscle (left)(2) 

8 
 
The central hypothesis for this study is that intercostal RPNI surgery significantly reduces chronic 
post-mastectomy pain with absence of painful neuroma recurrence. 
 
Aim 1: To examine the use of RPNI surgery to reduce post-mastectomy pain and opioid 
consumption. We will obtain patient-reported outcomes (PRO’s), using previously validated tools, to 
examine the effect of RPNI surgery on post-mastectomy pain and opioid use. Patients who are at least six 
months removed from mastectomy and exhibit clinical signs and symptoms of neuropathic pain will be 
asked to enroll in this IRB-approved study. Patients will be excluded if mastectomy occurred less than six 
months prior or if they have had previous surgical interventions to treat pain.  Upon completion of Aim 1, 
we will assess the association between intercostal RPNI surgery and neuropathic pain in post-mastectomy 
patients. 
 
Aim 2: To demonstrate absence of neuroma recurrence in post-mastectomy patients after 
intercostal RPNI surgery. Neuroma recurrence in patients treated with intercostal RPNI will be evaluated 
using physical exam findings and ultrasound (14, 17-20). Patients will be assessed immediately following 
enrollment, preoperatively, and at subsequent intervals (3 and 9 months) following RPNI. Upon completion 
of Aim 2, we will demonstrate that intercostal RPNI surgery provides durable relief from neuroma 
recurrence. 
 
2.4. Potential Risks and Benefits 
 
2.4.1. Potential Risks 
 
Risks related to study participation are minimal.  This study only evaluates chronic post-mastectomy pain 
in patients seeking a potential surgical intervention (RPNI). Risks of surgery are not considered part of the 
study and patients who are considering undergoing RPNI implantation, but later decide against it may still 
be included. Patients may feel inconvenienced when spending time on study requirements such as 
questionnaires. To minimize this risk, investigators have reviewed all survey instruments and reduced the 
questionnaire panel to minimally necessary items. To further reduce study time requirements, investigators 
have incorporated existing clinical measurements that are part of standard care and evaluation, such as 
physical exam and ultrasound measurements to collect outcomes data and avoid additional, study-only 
testing procedures. All study requirements and time commitments will be stated prior to enrollment. 
 
Additionally, as with many studies, there is a risk of confidentiality in participation. Although rare, the study 
team will take precautions to secure both hard copy and electronic data and train all study staff on the 
importance of data security and privacy. 
 
2.4.2. Known Potential Benefits 
 
The prescribing of opioid medications to treat pain, including chronic pain following surgery, has become a 
critical issue across the U.S. Reports indicate that 10% of opioid naïve patients who undergo mastectomy 
require opioids for pain relief at least three months after surgery and up to 40% of patients who undergo 
mastectomy report post-surgical pain lasting greater than three months. Three years after surgery, nearly 
25% of patients continue to report moderate persistent pain after the mastectomy procedure which 
involves the transection of small sensory nerves present and traveling through excised breast tissues. 
This study is a novel approach to improving post-mastectomy quality of life and reducing dependence on 
pain medications and the ensuing risk of dependence and addiction. 

9 
 
3. Hypotheses and Objectives 
 
Aim 1: To examine the use of RPNI surgery to reduce post-mastectomy pain and opioid 
consumption. 
 
3.1. Hypothesis: Neuroma resection and RPNI surgery to treat intercostal neuromas will reduce patient- 
reported post-mastectomy pain, depression/anxiety scores, and opioid use to a greater degree than will 
conservative neuropathic pain management. 
 
3.1.2. Objective: Identify patients with post-mastectomy pain who have been referred to the Multi- 
Disciplinary Peripheral Nerve (MDPN) or Plastic Surgery Clinics and evaluate their neuropathic pain, 
depression and anxiety levels, and opioid use pre- and post-treatment. 
 
We will enroll patients seeking surgical treatment for chronic post-mastectomy pain upon referral to our 
institutional Multi-Disciplinary Peripheral Nerve Pain (MDPN) Clinic or Plastic Surgery. The presence of 
neuropathic pain will be evaluated by the combined efforts of plastic surgeons, peripheral nerve surgeons, 
anesthesia pain providers, and physiatrists. Each patient’s medication usage will be logged at pre- and 
post-surgical timepoints. 
 
Aim 2: To demonstrate absence of neuroma recurrence in post-mastectomy patients after 
intercostal RPNI surgery. 
 
3.2. Hypothesis: Intercostal nerves treated with RPNI will remain free of neuroma recurrence through nine 
months after RPNI surgery. 
 
3.2.2. Objectives: Evaluate patient reported outcomes of intercostal RPNI surgery and clinical indicators 
such as routine ultrasound review and physical exam. 
 
3.3. Study Outcome Measures 
 
Upon successful execution of Aim 1, we will demonstrate that: 
 
1) RPNI surgery improves patient-reported physical and psychosocial well-being (patient reported 
depression and anxiety) within three months after surgery. 
 
2) Patients who undergo RPNI surgery will report reduced daily opioid consumption within 3 months after 
surgery. 
 
Upon successful execution of Aim 2, we will demonstrate that: 
 
1) RPNI surgery provides long-term protection from neuroma recurrence based on physical exam and 
ultrasound. 
 
4. Study Design 
 
4.1. Methodology: Patients seeking surgical consultation for RPNI surgery in the Multidisciplinary 
Peripheral Nerve Clinic for chronic post-mastectomy pain will be recruited for this study and followed 
longitudinally at four time points to evaluate pain, medication usage, anxiety and depression reporting 
compared to preoperative levels. 

10 
 
Upon enrollment, patients will complete baseline questionnaires including a self-reported medication log 
(Time 1) and continue their standard non-surgical management plan while awaiting surgery.  As an 
elective surgery, patients’ scheduled surgery dates usually occur approximately 3 months after initial 
consultation. Note: although investigators expect some variability on surgery scheduling, the average time 
of study involvement for each patient will be 12 months.  This represents approximately three months 
before surgery and nine months after surgery.   
 
Approximately two weeks prior to surgery (during the patient’s scheduled preoperative visit), participants 
will complete the panel of surveys, including medication log (Time 2) and again following RPNI 
implantation at three (Time 3) and nine months (Time 4) post procedure. The validated PRO instruments 
will be used to evaluate patients’ reported pain experiences, depression, and anxiety (see below). The 
medication logs will document the details of each patient’s medication use over time (see Appendix B 
Patient Medication log). Study duration will allow patients enrolled during the first 12 months to be 
followed for the entire study duration. 
 
Presence of neuropathic pain will be confirmed based on detailed history, physical exam findings (e.g. 
Tinel sign or pins/needles, burning, or shock-like sensations) and local anesthetic nerve blocks which 
are all part of routine assessment and evaluation at the clinic. 
 
4.2. Data Collection 
 
With the exception of 4.2.1. Patient Reported Outcome (PRO) instruments, all other collected data 
will be derived from standard clinical care for patients seeking surgical management of post-
mastectomy chronic pain. 
 
4.2.1. Patient Reported Outcome (PRO) instruments: As a specific type of pain, neurological pain or 
neuroma pain is typically reported as burning, stinging or tingling sensations. To distinguish between 
specific forms of pain in patients reporting chronic post-mastectomy pain,  a broad scope of pain 
dimensions will be measured using the following validated instruments: 
1.Short-form McGill Pain Questionnaire (SF-MPQ-2) to characterize patients’ pain experience (33-35). 
SF-MPQ-2 has been validated for use in clinical trials studying neuropathic pain (31-33).  
2. Patient-Reported Outcomes Measurement Information System or PROMIS instruments (36) will 
measure Pain Intensity(37), Pain Interference(38), and Neuropathic Pain Quality (39)  
3. The Pain Catastrophizing Scale (PCS) – will measure pain catastrophizing, or an exaggerated reaction 
to pain or anticipated pain thought to play a role in chronic pain reporting. 
(https://www.practicalpainmanagement.com/pain/other/co-morbidities/pain-catastrophizing-what-
clinicians-need-know).  
4. The Patient Health Questionnaire (PHQ) (40) – measures the patient’s reported depression level. 
5. The Generalized Anxiety Disorder measure (GAD-7) evaluates anxiety (41).  
6. The West Have-Yale Multidimensional Pain Inventory (WHYMPI)- provides a brief psychometrically-
sound, and comprehensive assessment of the components of chronic pain. (Kerns, R.D., Turk, D.C., & 
Rudy, T.E. (1985). The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain, 23, 345-
356.) 
7. Self-Reported socio-demographic questions such as highest educational level attained, and marital 
status will be included in both the baseline and 9-month postoperative time points. 
 
Please see Appendix A for instruments. 
 
4.2.2. Pain Medication Use: Because prescribed dosage of medications may differ from actual usage, 
details of each patient’s pre- and post-operative pain medication use will be documented at each study time 
point using a self-reported medication log. The log will be integrated with the study questionnaires.  Study 

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13 
 
prior to Month 1 so Phase 2 (enrollment) will begin as soon as possible. 
 
Phase 2: Months 1-12 of the study will be dedicated to the enrollment and initial follow-up of the RPNI 
study subjects. All enrollment of subjects will be completed by Month 12 to allow for a complete follow-up 
period for all patients including an approximate 3 month preoperative and 9 month postoperative period. 
Additionally, periodic process evaluation and data auditing will occur to assure adherence to study 
protocol, timeline and sample size goals. Initial data analysis will take place at this time, including 
descriptive statistics for the study population. 
 
Phase 3: Months 13-24 of the study will involve the conclusion of follow-up data collection for study 
patients and RPNI surgery for patients enrolled during months 9-12. Data will be reviewed for 
completeness and cleaned for analysis by the study’s biostatistician. Dissemination of study findings will 
begin during this phase. 
 
Final analyses, report generation, and manuscript submission will take place in the 3-6 months following 
completion of the funded study during a no-cost extension period. 
 
6.2. Schedule of Events for Enrolled Patients 
 
 
  Time 1  
  Time 2  
  Time 3  
Time 4  
Baseline Visit 
       Preop Visit 
3 Months 
Post Visit 
9 Months 
Post Visit 
PRO’s 
X 
X 
X 
X 
Pain Measures 
X 
X 
X 
X 
CDL 
X 
X 
X 
X 
Med Log 
X 
X 
X 
X 
Physical Exam 
X 
X 
X 
X 
Ultrasound* 
X 
X 
* results recorded from routine diagnostic care 
 
Time 1 – Baseline 
 
Enrollment: Immediately following the initial consultation, the site coordinator will be available to meet with 
patients to describe the study. If in-person enrollment is not possible, the site coordinator will contact the 
patient via telephone and if interested mail a study packet with consent documents to the patient-provided 
mailing address. The coordinator will provide a full description of the study, answer questions, and obtain 
written informed consent in accordance with the IRB-approved protocol. Each patient will follow their 
standard non-surgical treatment plan of NSAIDs, neuropathic analgesics, opioids, and physical therapy 
until the surgery, estimated to be about three months. 
 
Patient Reported Outcomes (PRO’s): Patients will be asked to complete the study’s initial panel of 
questionnaires including a demographic survey, questions about pain experience, anxiety and 
depression. 
 
Medication Log: Each patient will complete a medication log (integrated with the PRO surveys) to record 
all medications currently being used. See Appendix B for log. 
 

14 
 
Clinical Data Log: The site coordinator will also collect key clinical data such as date of mastectomy, 
previous pain management therapy, ultrasound results and comorbidities. These data will be captured 
through the University’s electronic medical records system and entered into the study’s database. 
 
Time 2 - Preoperative 
 
Patient Reported Outcomes (PRO’s): Preoperatively, patients will be asked to complete the study’s panel 
of questionnaires describing self-reported pain experience, anxiety and depression and socio-
demographic characteristics. 
 
Medication Log: Each patient will complete a medication log (integrated with the PRO surveys) to record all 
medications currently being used. See Appendix B for log. 
 
Clinical Data Log: The site coordinator will also collect additional clinical data such as changes in health 
history, ultrasound results and details of the pre-operative pain management. These data will be captured 
through the University’s electronic medical records system and entered into the study’s database. 
 
Time 3 – Three Months Post-Surgery 
 
Patients will be scheduled for a 3-month post-surgical visit at the peripheral nerve clinic. During this visit, 
the following data will be collected. 
 
Patient Reported Outcomes (PRO’s): Patients will be asked to complete the study’s panel of 
questionnaires describing self-reported pain experience, anxiety and depression. 
 
Medication Log: Each patient will complete a medication log (integrated with the PRO surveys) to record all 
medications currently being used. See Appendix B for log. 
 
Clinical Data Log: The site coordinator will also collect additional clinical data such as changes in health 
history, ultrasound results, surgical detail, and surgical complications. These data will be captured through 
the University’s electronic medical records system and entered into the study’s database. 
 
Time 4 – Nine Months Post-Surgery  
 
Patients will be scheduled for a 9-month post-surgical visit at the peripheral nerve clinic. During this visit, 
the following data will be collected. 
 
Patient Reported Outcomes (PRO’s): Patients will be asked to complete the study’s panel of 
questionnaires describing self-reported pain experience, anxiety and depression and socio-
demographic characteristics. 
 
Medication Log: Each patient will complete a medication log to record all medications currently being used. 
See Appendix B for log. 
 
Clinical Data Log: The site coordinator will also collect additional clinical data such as changes in health 
history, ultrasound results, complications and details of the post-operative pain management regimen. 
These data will be captured through the University’s electronic medical records system and entered into 
the study’s database. 
 
7. Assessment of Safety 
 

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17 
 
 
The investigator will ensure that this study is conducted in full conformity with the principles set forth in The 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, as 
drafted by the US National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the ICH E6; 62 Federal 
Regulations 25691 (1997) and the Declaration of Helsinki and Good Clinical Practice (GCP). 
 
11.2. Institutional Review Board 
 
Study investigators will obtain approval to conduct research from the University of Michigan’s Institutional 
Review Board (IRB). All protocol amendments will be IRB approved prior to implementing, except when 
the change is for patient safety. 
 
11.3. Informed Consent Process 
 
Discussion of risks and possible benefits of this study participation will be provided to the subjects. 
Consent forms will be IRB-approved and the subject will be asked to read and review the document. Upon 
reviewing the document, the investigator will explain the research study to the subject and answer any 
questions that may arise. The subject will sign the informed consent document prior to any procedures 
being done specifically for the study. The subjects will have the opportunity to discuss the study with their 
surrogates or think about it prior to agreeing to participate.  The subjects may withdraw consent at any 
time throughout the course of the trial. A copy of the informed consent document will be given to the 
subjects for their records. The rights and welfare of the subjects will be protected by emphasizing to them 
that the quality of their medical care will not be adversely affected if they decline to participate in this study. 
The consent process will be documented in detail in the participants source documents by the individual(s) 
who conducted the consenting process. 
 
11.4. Exclusion of Women, Minorities, and Children (Special Populations) 
 
None. 
 
11.5. Subject Confidentiality 
 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. The study protocol, documentation, data, and all other information generated 
will be held in strict confidence. 
 
Any data, specimens, forms, reports, and other records that leave the site will be de-identified of any 
protected health information (PHI) and replaced with study identifier to maintain subject confidentiality. 
Information will not be released without written permission of the participant, except as necessary for 
monitoring by IRB, the FDA, OHRP and/or any other government officials, safety monitors/committees that 
may need the information to make sure that the study is done in a safe and proper manner, learn more 
about side effects, and/or analyze the results of the study; insurance companies or other organizations that 
may need the information in order to pay medical bills or cost of study participation. 
 
12. Data Handling and Record Keeping 
 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of the data 
reported. All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
 

18 
 
 
12.1. Data Management Responsibilities 
 
The study will be managed Plastic Surgery’s Research Specialist, Jennifer Hamill. She will be responsible 
for the data management SOP’s development and adherence. She will also be responsible for database 
development using the REDCap data capture system described below. 
 
12.2. Data Capture Methods 
 
Data capture, verification, and disposition: Data Capture will be collected using REDCap (Research 
Electronic Data Capture). REDCap is a secure web application designed to support data capture for 
research studies. It provides user-friendly web-based case report forms, real-time data entry with 
branching logic and validation (e.g. for data types and range checks), audit trails, a de-identified data 
export mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus), procedures for 
importing data from external sources, and advanced features such as a data quality check module. The 
system was developed by a multi-institutional consortium initiated at Vanderbilt University (http://project- 
redcap.org/). By using a web application, all members of the study team will be able to easily and 
effectively contribute to and manage their data. An aggregate, de-identified database will be created once 
data collection is complete for each study aim. 
 
REDCap servers are physically located in the University of Michigan MSIS data center. Application and 
database servers are on virtual machines (VM). The VM servers are Red Hat Enterprise Linux Server 5.6 
(64-bit, 2.6.18 238 e15-smp kernel) 2x AMD Opteron 6174 5.0.95 2.2 GHz with 4 GB RAM, running 
Apache 2.2.3 (application servers) and MySQL (database servers). Physical security for the databases is 
provided in a professionally managed and equipped tier-2 data center with tightly controlled access. 
Remote data access employs SSL encryption and 2-tier Kerberos/Level 1 and UMHS Level 2 password 
challenges via LDAP authentication. Access to the application, the database, and the underlying systems 
infrastructure are consistent with industry best practices including HIPAA security and privacy 
requirements and the HITECH Act. The application provides audit trails on user access to MICHR and 
MSIS technical and support teams. Backup of data is managed by MSIS and vulnerability testing is 
performed regularly by the University of Michigan Health System Medical Center Information Technology. 
Risk evaluation is performed using a methodology derived from NIST Special Publication 800-53 – 
“Recommended Security Controls for Federal Information Systems” and is used to refine and improve 
operating policies and procedures. 
 
Daily backups and VM snapshots of the application and database servers are stored on a remote storage 
device. The restoration of the servers from a hardware or software failure is protected for 24 hours for 
disaster recovery. REDCap data collection projects rely on a thorough, study-specific data dictionary 
defined in an iterative, self-documenting process by all members of the research team. This iterative 
development and testing approach results in a well-planned and implemented data collection strategy for 
individual studies. REDCap is flexible enough to be used for a variety of research types including multi-site 
clinical research trials and provides an intuitive user interface for database design and data entry. External 
collaborators given access to REDCap by the project lead are given Level 1/Level 2 password access. 
Access to the REDCap study database is provided only through a virtual private network (VPN) to the 
University of Michigan providing an additional layer of encryption and security of data in addition to 
encryption via REDCap. Data downloaded from REDCap for statistical analysis will be stored on MSIS 
servers in password protected folders with access restricted to UM project personnel and controlled by the 
PI’s. External drives are password protected and are backed up nightly. Individual access to file storage is 
controlled through Level 1 passwords and is accessible only to UM personnel. Electronic data files are 
deleted from servers at the end of the project; backed up copies of the data files are retained for a short 
period of time (several weeks) and can be recalled by project personnel if desired. After several weeks, the 

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20 
 
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2. 
Kung TA, Langhals NB, Martin DC, Johnson PJ, Cederna PS, Urbanchek MG. Regenerative peripheral 
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PMC4405062. 

21 
 
12. 
Waltho D, Rockwell G. Post-breast surgery pain syndrome: establishing a consensus for the definition of 
post-mastectomy pain syndrome to provide a standardized clinical and research approach - a review of 
the literature and discussion. Canadian journal of surgery Journal canadien de chirurgie. 2016;59(5):342- 
50. PubMed PMID: 27668333; PubMed Central PMCID: PMC5042722. 
 
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Jung BF, Ahrendt GM, Oaklander AL, Dworkin RH. Neuropathic pain following breast cancer surgery: 
proposed classification and research update. Pain. 2003;104(1-2):1-13. PubMed PMID: 12855309. 
 
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Brackstone M. A review of the literature and discussion: establishing a consensus for the definition of 
post-mastectomy pain syndrome to provide a standardized clinical and research approach. Canadian 
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Central PMCID: PMC5042712. 
 
15. 
Urbanchek MG, Kung TA, Frost CM, Martin DC, Larkin LM, Wollstein A, et al. Development of a 
Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb. BioMed research 
international. 2016;2016:5726730. doi: 10.1155/2016/5726730. PubMed PMID: 27294122; PubMed 
Central PMCID: PMC4886043. 
 
16. 
Ursu DC, Urbanchek MG, Nedic A, Cederna PS, Gillespie RB. In vivo characterization of regenerative 
peripheral nerve interface function. Journal of neural engineering. 2016;13(2):026012. doi: 10.1088/1741- 
2560/13/2/026012. PubMed PMID: 26859115. 
 
17. 
Lee KS. Musculoskeletal ultrasound: how to evaluate for Morton's neuroma. AJR American journal of 
roentgenology. 2009;193(3):W172. doi: 10.2214/AJR.09.3110. PubMed PMID: 19696252. 
 
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Chen KH, Lee KF, Hsu HC, Huang WC, Hsiao KY, Fang KM. The role of high-resolution ultrasound in the 
diagnosis of a traumatic neuroma in an injured median nerve. American journal of physical medicine & 
rehabilitation. 2009;88(9):771-4. doi: 10.1097/PHM.0b013e3181b332ef. PubMed PMID: 19692793. 
 
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Ernberg LA, Adler RS, Lane J. Ultrasound in the detection and treatment of a painful stump neuroma. 
Skeletal radiology. 2003;32(5):306-9. doi: 10.1007/s00256-002-0606-9. PubMed PMID: 12719933. 
 
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nerve stumps of transected peripheral nerves on the development of neuroma (experimental study). 
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Central PMCID: PMC2527232. 
 
22. 
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by proximal relocation. Journal of hand surgery. 2004;29(4):338-50. doi: 10.1016/j.jhsb.2004.01.005. 
PubMed PMID: 15234497. 
 
23. 
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extremity neuromas. Journal of reconstructive microsurgery. 1995;11(3):175-7. doi: 10.1055/s-2007- 
1006527. PubMed PMID: 7650641. 
 
24. 
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extremity neuromas. The Journal of hand surgery. 1995;20(2):221-6. doi: 10.1016/S0363- 
5023(05)80011-5. PubMed PMID: 7775755. 

22 
 
25. 
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comparing neuroma formation in rat. International surgery. 2014;99(6):807-11. doi: 10.9738/INTSURG-D- 
13- 00184.1. PubMed PMID: 25437591; PubMed Central PMCID: PMC4254244. 
 
26. 
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traditional and newer methods. The Journal of hand surgery. 1976;1(2):144-51. PubMed PMID: 1032972. 
 
27. 
Yuksel F, Kislaoglu E, Durak N, Ucar C, Karacaoglu E. Prevention of painful neuromas by epineural 
ligatures, flaps and grafts. British journal of plastic surgery. 1997;50(3):182-5. PubMed PMID: 9176005. 
 
28. 
Dorsi MJ, Lambrinos G, Dellon AL, Belzberg AJ. Dorsal rhizotomy for treatment of bilateral intercostal 
neuralgia following augmentation mammaplasty: case report and review of the literature. Microsurgery. 
2011;31(1):41-4. doi: 10.1002/micr.20828. PubMed PMID: 21207497. 
 
29. 
Williams EH, Williams CG, Rosson GD, Heitmiller RF, Dellon AL. Neurectomy for treatment of intercostal 
neuralgia. The Annals of thoracic surgery. 2008;85(5):1766-70. doi: 10.1016/j.athoracsur.2007.11.058. 
PubMed PMID: 18442581. 
 
30. 
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from a long-term Regenerative Peripheral Nerve Interface. Conference proceedings : Annual International 
Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and 
Biology Society Annual Conference. 2014;2014:1989-92. doi: 10.1109/EMBC.2014.6944004. PubMed 
PMID: 25570372. 
 
31. 
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Reconstruction: One-year Outcomes of the Mastectomy Reconstruction Outcomes Consortium (MROC) 
Study. Annals of surgery. 2018;267(1):164-70. doi: 10.1097/SLA.0000000000002033. PubMed PMID: 
27906762. 
 
32. 
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contains increased levels of semaphorin 3A, which surrounds nerve fibers and reduces neurite extension 
in vitro. The Journal of neuroscience : the official journal of the Society for Neuroscience. 
2007;27(52):14260-4. doi: 10.1523/JNEUROSCI.4571-07.2007. PubMed PMID: 18160633. 
33. 
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299. PubMed PMID: 1235985. 
 
34. 
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35. 
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initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF- 
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36. 
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23 
 
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38. 
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39. 
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42. 
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45. 
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46. 
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47. 
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doi: 10.1002/hbm.20641. PubMed PMID: 18711711. 

24 
 
APPENDIX A: PATIENT REPORTED OUTCOMES INSTRUMENTS 
 
 
Surgical treatment of post-surgical mastectomy pain utilizing the regenerative peripheral nerve 
interface (RPNI) 
 
Thank you for participating in this Chronic Post-Mastectomy Pain study. Please answer a few 
questions about yourself below. 
 
1. What is your date of birth? 
(mm/dd/yyyy) 
 
2. Which of the following categories best describes your current marital status? 
o Married 
o Living with significant other 
o Widowed 
o Separated 
o Divorced 
o Single, never married 
 
3. What is the last level of education you have completed? 
o Some high school 
o High school diploma 
o Some college, trade or university 
o College, trade or university degree 
o Some Master/Doctoral work 
o Master/Doctoral degree 
 
4. What is your main activity or work situation? 
o Employed full-time 
o Employed part-time 
o Volunteer work 
o Homemaker 
o Student 
o Retired 
o Unable to work/disabled 
o Unemployed/seeking  employment 
o Other (Please specify)   
 
 
 
5. Can you estimate your annual gross household income? 
o Less than $25,000 
o $25,000 - $49,999 
o $50,000 - $74,999 
o $75,000 - $99,000 

29 
 
o $100,000 or more 
 
7. How would you best describe your race? 
o American Indian/Alaska Native 
o Asian 
o Native Hawaiian or Other Pacific Islander 
o Black or African American 
o White 
 
8. How would you best describe your ethnic background (please choose one)? 
o Hispanic or Latino 
o Not Hispanic or Latino 
 
 
PHQ-9 
 
 
Over the last 2 weeks, how often have you been bothered by any of the following problems (circle one 
number on each line). 
 
 
How often during the past 2            Not at all        Several days       More than             Nearly everyday 
weeks were you bothered by...                                                             half the days   
 
  
1. Little interest or pleasure in doing things............. 0                       1                          2                          3 
 
 
2. Feeling down, depressed, or hopeless ..............    0                       1                          2                          3 
 
 
3. Trouble falling or staying asleep, or 
sleeping too much..............................................          0                      1                          2                        3 
 
 
4. Feeling tired or having little energy .................... 0                       1                          2                          3 
 
 
5. Poor appetite or overeating................................   0                       1                          2                           3 
 
 
6. Feeling bad about yourself, or that you 
are a failure, or have let yourself or 
your family down...............................................       0                       1                         2                          3 
 
 
7. Trouble concentrating on things, such as 
reading the newspaper or watching 
television............................................................         0                       1                         2                          3 
 

29 
 
 
8. Moving or speaking so slowly that other 
people could have noticed. Or the opposite – 
being so fidgety or restless that you have 
been moving around a lot more than usual........         0                        1                         2                          3 
 
 
9. Thoughts that you would be better off dead, 
or of hurting yourself in some way .....................       0                        1                         2                          3 
 
 
General Anxiety Scale-7 (same instructions and response format) 
 
 
10. Feeling nervous, anxious or on edge ……...        0                        1                         2                          3 
 
 
11. Being unable to stop or control worrying …        0                        1                         2                          3 
 
How often during the past 2            Not at all        Several days       More than             Nearly everyday 
weeks were you bothered by...                                                             half the days   
  
 
12. Worrying too much about different things…   0                        1                           2                                3 
  
13. Having trouble relaxing……………………    0                        1                           2                                3 
 
14. Being so restless that it is hard to sit still….    0                        1                           2                                3 
 
15. Becoming easily annoyed or irritable……      0                        1                           2                                 3 
 
16. Feeling afraid, as if something awful  
      might happen……………………………       0                        1                           2                                 3 
 
 
 
 
 
If you feel you may be experiencing signs of anxiety or depression you are not alone. Here are some 
resources for help: 
• 
Depression Toolkit: https://www.depressioncenter.org/depression-toolkit  

29 
 
• 
Michigan Medicine’s PsychOncology Clinic (877) 907-0859 offering services for any patient 
receiving care through the Rogel Cancer Center 
(https://www.rogelcancercenter.org/support/managing-emotions/psychoncology).  
• 
Suicide Hotline – 1-800-784-2433 
• 
Psychiatric Emergency Services, University of Michigan (734) 936-5900 Serving Washtenaw 
County, Service available 24 hours a day, seven days a week. 
 
 
 
 
 

30 
 
Pain Interference – Short Form 6a 
 
Please respond to each question or statement by marking one box per row. 
 
 
In the past 7 days… 
Not at all 
A little bit  Somewhat  Quite a bit       Very much 
PAININ9 
1 
How much did pain interfere with your ¨ 
¨ 
¨ 
¨ 
¨ 
day to day activities? 
1 
2 
3 
4 
5 
 
PAININ22 
2 
 
PAININ31 
3 
 
PAININ34 
4 
 
PAININ12 
5 
 
PAININ36 
6 
How much did pain interfere with work ¨ 
¨ 
¨ 
¨ 
¨ 
around the 
1 
2 
3 
4 
5 
How much did pain interfere with 
¨ 
¨ 
¨ 
¨ 
¨ 
your ability to participate in social 
1 
2 
3 
4 
5 
How much did pain interfere with your ¨ 
¨ 
¨ 
¨ 
¨ 
household 
1 
2 
3 
4 
5 
How much did pain interfere with the ¨ 
¨ 
¨ 
¨ 
¨ 
things you usually do for fun? 
1 
2 
3 
4 
5 
How much did pain interfere with your ¨ 
¨ 
¨ 
¨ 
¨ 
enjoyment of social 
1 
2 
3 
4 
5 
 
Pain Intensity 
– Scale 
 
Please respond to each item by marking one box per row. 
 
 
In the past 7 days… 
Had 
  
no 
 
Very 
Mild 
Moderate 
Severe      severe 
PAINQU6 
How intense was your pain at its 
worst?.... 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
PAINQU8 
How intense was your average 
pain?......... 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
No pain 
Mild 
Moderate 
Severe 
Very 
severe 
PAINQU21 
What is your level of pain right 
now?........ 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 

31 
 
Neuropathic Pain Quality 5a 
Please respond to each question or statement by marking one box per row. 
In the past 7 days… 
 
Not at 
all 
A little 
bit 
Some 
what 
Quite 
a bit 
Very 
much 
 
PAQUA 
Did your pain feel like pins and ¨ ¨ 
¨ 
¨ 
¨ 
needles? 
1 
2 
3 
4 
5 
L27r
PAQUAL14r Did your pain feel tingly? 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
PAQUAL21r Did your pain feel 
stinging?....................... 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
PAQUAL31r Did your pain feel electrical? 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
PAQUAL11r Did your pain feel 
numb?........................... 
¨ 
1 
¨ 
2 
¨ 
3 
¨ 
4 
¨ 
5 
 
 
PAIN CATASTROPHIZING SCALE (PCS) 
 
We are interested in looking at the relationship between thoughts and pain. Please 
indicate the degree to which you have experienced each of the following thoughts or 
feelings when experiencing pain by circling a number under each statement. 
When I feel pain... 
1. I worry all the time about whether the pain will end. 
0 
1 
2 
3 
4 
 
Not at all 
All the time 
 
2. I feel I can't go on. 
0 
1 
2 
3 
4 
 
Not at all 
All the time 
 
3. It's terrible and I think it’s never going to get any better. 
0 
1 
2 
3 
4 

32 
 
 
Not at all 
4.  It's awful and I feel that it overwhelms me. 
All the time 
0 
1 
2 
3 
4 
Not at all 
All the time 
5.  I feel I can't stand it anymore. 
0 
1 
2 
3 
4 
Not at all 
All the time 
6.  I become afraid that the 
0 
1 
pain may get worse. 
2 
3 
4 
Not at all 
All the time 
7.  I think of other painful experiences. 
0 
1 
2 
3 
4 
Not at all 
All the time 
8.  I anxiously want the pain to go away. 
0 
1 
2 
3 
4 
Not at all 
All the time 
9.  I can’t seem to keep it out of my mind. 
0 
1 
2 
3 
4 
Not at all 
All the time 
10. I keep thinking about how much it hurts. 
0 
1 
2 
3 
4 
Not at all 
All the time 
 
11. I keep thinking about how badly I want the pain to stop. 

33 
 
0 
1 
2 
3 
4 
 
Not at all 
All the time 
12. There is nothing I can do to reduce the intensity of the pain. 
0 
1 
2 
3 
4 
Not at all 
All the time 
 
13. I wonder whether something serious may happen. 
0 
1 
2 
3 
4 
 
Not at all 
All the time 

34 
 
 

35 
 
 

36 
 
 

37 
 
 

38 
 
 

39 
 
 

40 
 
 

41 
 
APPENDIX B: PATIENT-
REPORTED MEDICATION LOG 
Medication Log 
Thank you for participating in this study. Please provide a complete list of all 
medications you are taking or have taken in the past month. Please include 
any over-the-counter medications (e.g., Tylenol, Aleve) and alternative 
therapies (e.g., marijuana). Try your best to list the medications as you are 
actually taking them (which may differ from how the prescription is actually 
written). 
Name: 
Medication Name 
Date 
Started 
Dose 
(for example: 5mg 
OR 0.125mcg) 
Frequency 
(for example: 2 pills 
twice daily 
OR half a pill once a 
week) 
 
 
 
 

41 
 
 
 
APPENDIX C: CLINICAL 
MEDICATION LOG BASED ON 
PATIENT PROVIDED 
MEDICATION USAGE- DRAFT 
 

41 
 

41