bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Angle of Contralateral Oblique View
in Cervical Interlaminar Epidural Injection
Depending on the Needle Tip Position
Authors: Hun Suh Jeong Hun
Published: October 2019

Background: Chronic neck and upper extremity pain associated with cervical origin is common, and
cervical interlaminar epidural steroid injections (CILESIs) are frequently used to manage the symptoms
of cervical spinal disorders. However, CILESIs are associated with risks such as dural puncture and
cord injury.
Objectives: We aimed to determine the optimal needle tip visualization, in order to minimize
CILESIs-induced complications.
Study Design: Retrospective observational study.
Setting: The single center study in Seoul, Republic of Korea.
Methods: Participants were 312 adults with neck or upper extremity pain caused by cervical lesion
such as cervical herniated nucleus pulposus (HNPs). They underwent magnetic resonance imaging
(MRI). Patients with severe cervical spinal stenosis, prior posterior cervical spine surgery, or other
anatomical abnormalities of the vertebral laminae were excluded from the study. By using axial T2-
weighted spin-echo MRI, we defined the area between the spinous processes as the anterior posterior
zone 1 (APZ1), and the area lateral to the spinous processes as the anterior posterior zone 2 (APZ2).
Line 1 was drawn along the ventral margin of lamina that confined APZ1, and line 2 was similarly
drawn in order to define APZ2. The angles between the midsagittal line and lines 1 and 2 were
defined as angle 1 and angle 2, respectively. Angles were measured at the C5-6, C6-7, and C7-T1
levels, on both right and left sides at each level.
Results: Angle 1 values (in degrees) at right C5-6, left C5-6, right C6-7, left C6-7, right C7-T1, and
left C7-T1 were 62.54 ± 10.52, 64.34 ± 9.86, 62.03 ± 10.27, 62.87 ± 10.64, 61.64 ± 11.0, and
62.58 ± 10.83, respectively. Angle 2 values at right C5-6, left C5-6, right C6-7, left C6-7, right C7-
T1, and left C7-T1 were 50.44 ± 6.84, 50.77 ± 7.00, 49.15 ± 6.07, 49.89 ± 6.45, 50.84 ± 6.68, and
50.24 ± 6.60, respectively. There were significant differences between angles 1 and 2 at each level.
Limitations: This study is a retrospective review and did not employ controls, blinding, or
randomization. Additionally, the optimal CLO angles for CILESIs and cervicothoracic interlaminar
epidural steroid injections (CTILESIs) have not been assessed in clinical studies. Another limitation is
that we divided lamina into only APZ1 and APZ2.
Conclusions: During CILESIs, a contralateral oblique (CLO) view at 60 degrees is superior to other
angles for visualizing the epidural space when the needle tip is placed in the interlaminar space and
within the spinous processes margin. When the needle tip is placed in the interlaminar space and
lateral to the spinous processes, a CLO view at 50 degrees is most appropriate.
Institutional Review Board (IRB) approval number: S2016-0390-0001
Key words: Chronic neck pain, chronic upper extremity pain, cervical epidural injections, cervical
interlaminar steroid injections, steroid, needle tip position, needle tip visualization, fluoroscopy,
complication, contralateral oblique view
Sacroiliac Joint Intraarticular Injection in True
Anteroposterior View: Description of a New
C-Arm Guided Method
Authors: Shaabani Sanaz
Published: October 2019

Background: The anatomic characteristics of the sacroiliac joint (SIJ) make it difficult
to achieve intraarticular injection without radiologic guidance. The classic C-arm guided
SIJ intervention technique is difficult. Here we describe a new and simple method for SIJ
intraarticular intervention.
Objective: This study aims to introduce a new, simple approach for SIJ intraarticular
intervention.
Study Design: An observational case series study.
Setting: The study was conducted at an academic medical center in a major metropolitan city.
Methods: This method of intervention was performed on 57 patients (a total of 73 joints)
who were selected for diagnostic and therapeutic SIJ intervention. The procedure was done
in anteroposterior (AP) view, without any C-arm angulation. The accuracy of the intraarticular
injection was confirmed by using intraarticular contrast material. A numerical rating scale
(NRS) score was recorded for each joint before and after the procedure; the number of x-ray
exposures and number of attempts were recorded for each procedure as well.
Results: Successful intraarticular contrast spread was obtained in all SIJs. The number of
x-ray exposures was about 9 ± 3, and there was not a remarkable difference between cases
according to gender of the patient (P = 0.1) or side of the joint (P = 0.2). In 5 cases, the first
needle placement was not correct; there were no differences between gender (P = 0.4) and
side of the joint (P = 0.4) regarding the first successful attempt. The NRS pain scores decreased
in all of the patients more than 50% after the procedure; the pain scores were similar to the
results of classic methods of intraarticular interventions with successful contrast spread, and
there were no remarkable differences considering gender (P = 0.5) or side of the joint (P = 0.8).
Limitations: This is a very small, nonrandomized, and controlled study; further blinded
clinical trials are needed to clarify the probable advantages of this method compared with
conventional ones.
Conclusion: This observational study introduces a new and simple approach for SIJ
intraarticular intervention, with a high success rate.
Key words: Low back pain, sacroiliac joint, C-arm, new technique, intraarticular, injection
The Termination Level of the Dural Sac Relevant
to Caudal Epidural Block in Lumbosacral
Transitional Vertebrae: A Comparison between
Sacralization and Lumbarization Groups
Authors: Jeong Yu Mi
Published: October 2019

Background: Lumbosacral transitional vertebrae (LSTV) are a relatively common variant and have
been considered as one of the reasons for back pain. It is not unusual for clinicians to encounter
patients with LSTV who require caudal epidural block (CEB) for pain management.
Objective: We investigated the termination level of the dural sac (DS) and anatomical features
of the lumbosacral region relevant to CEB in patients with LSTV and compared these findings
between sacralization and lumbarization groups.
Study Design: A retrospective evaluation.
Setting: A university hospital with inpatient and outpatient LSTV cases presenting low back pain.
Methods: Four hundred ninety-four LSTV patients were included and categorized into sacralization
(n = 201) or lumbarization groups (n = 293). Magnetic resonance imaging (MRI) of all of the LSTV
patients were reviewed to determine the level of DS termination, the shortest distance between
the apex of the sacral hiatus and DS, and the presence and the caudal level of sacral perineural
cysts. Each lumbosacral vertebra column was divided into 3 equal portions (upper, middle, and
lower thirds). The MRI findings in both of the groups were compared and analyzed.
Results: The distribution frequency of the levels of DS termination demonstrated a significant
difference between the 2 groups. The mean caudal DS level in the lumbarization group was
significantly lower than the sacralization group (lower third of the S2 [131 {44.7%} of 293 patients]
vs. lower third of the S1 [78 {38.8%} of 201 patients]). The DS terminated at the S3 in more than
19% of the lumbarization group, whereas in only one case of the sacralization group. Although
the incidence of perineural cysts was not significantly different between the 2 groups, the mean
level of caudal margin of perineural cysts in the lumbarization group was significantly lower than
the sacralization group (middle third of the S3 [10 {35.7%} of 28 cases] vs. middle third of the S2
[11 {44%} of 25 cases]).
Limitations: This study reveals several limitations including the practical challenge of accurate
enumeration of the transitional segment and the constraints on generalizability posed by the
single-country study.
Conclusion: When planning CEB for patients with LSTV, pre-procedural MRI to check the
anatomical structures, including the level of DS termination and caudal margin of perineural cysts,
would be of great use for lowering the risk of unexpected dural puncture during the procedure,
especially in the lumbarization cases.
Key words: Termination of the dural sac, dural sac termination, lumbosacral transitional
vertebrae, transitional vertebra, caudal epidural block
A Case Report on Red Ear Syndrome with
Tinnitus Successfully Treated with Transcranial
Random Noise Stimulation
Authors: Kreuzer Peter M.
Published: October 2019

Background: The red ear syndrome represents a rare symptom complex consisting of auricular
erythema associated with painful and burning sensations. It has been described in combination
with tinnitus rarely. It has been hypothesized to be etiologically related to altered trigeminal afferent
input, temporomandibular disorders, and thalamic dysfunction.
Objectives: The initial objective of applying transcranial random noise stimulation (tRNS) in a
case of red ear syndrome in combination with tinnitus was the alleviation of the phantom sounds.
Study Design: This is a case report on the successful treatment of red ear syndrome with tinnitus
by means of transcranial random noise stimulation (tRNS) and a short review on the published cases
of this condition.
Setting: We present the case of a 50-year-old woman reporting a simultaneous onset of constant
left-sided tinnitus and feelings of warmth accompanied by an intermittent stabbing and/or
oppressive pain stretching from the ipsilateral ear to the head/neck/shoulder region, occasionally
accompanied by nausea/vomiting and dizziness. After failure of pharmacological treatment attempts,
either because of lacking clinical effects (gabapentin, zolmitriptan, and indomethacin) or because
of adverse reactions (pregabaline), the patient was offered an experimental neuromodulatory
treatment with bitemporal tRNS primarily targeting the tinnitus complaints of the patient.
Methods: tRNS was conducted in 2 – 3 day sessions (stimulation site: bilateral temporal
cortex/2.0 mA/10 s on-and-off-ramp/offset 0 mA/20 min/random frequencies 101 – 640Hz /
NeuroConn Eldith DC-Stimulator plus).
Results: In 3 consecutive pain attacks repeated sessions of tRNS resulted in substantial alleviation
of pain intensity and a prolongation of the interval between attacks. This was an expected finding
as the proposed tRNS treatment was initially offered to the patient aiming at an alleviation of the
tinnitus complaints (which remained unaffected by tRNS).
Limitations: The reported data derive from compassionate use treatment in one single patient.
Application of a sham condition would have been desirable, but is not possible in the context of
compassionate use treatment. Nevertheless, we would consider it rather unlikely that the reported
effects are purely unspecific as the patient did exclusively report symptom alleviation of pain-related
parameters without affecting the tinnitus.
Conclusions: This case report demonstrates the feasibility and therapeutic potential of applying
neuromodulatory treatment approaches in red ear syndrome, a rare form of trigemino-autonomal
headache. Therefore, it deserves detailed observation in clinical routine applications as well as
controlled trials further investigating its neurobiological effects.
Key words: Red ear syndrome, pain, trigemino-autonomal headache, chronic tinnitus,
transcranial electrical stimulation, random noise stimulation
Reliability and Safety of Contra-Lateral
Oblique View for Interlaminar Epidural Needle
Placement
Authors: Derby Richard
Published: October 2019

Cord trauma is a risk with a cervical and thoracic interlaminar epidural approach to the epidural
space. Intermittent lateral fluoroscopic imaging to detect needle depth is often cumbersome and
may be difficult to interpret. In comparison, the contra-lateral oblique (CLO) fluoroscopic view is
efficient and easy to interpret. However, the in vivo reliability and safety of this technique has not
been formally investigated.
The senior author collected fluoroscopic images on 278 consecutive patients undergoing an
interlaminar epidural block at the T1-T2 level performed using a 17 gauge Tuohy needle. Before
catheter placement, anterior-posterior (AP) and CLO fluoroscopic images were saved with the
needle at the ligamentum flavum and the needle just through the ligamentum flavum.
We randomly selected the images of 40 cases that included the paired CLO images (total 80
images) documenting the views at and through the ligamentum flavum. Three interventionalists
were asked to review, in a blinded fashion, the randomly selected, paired CLO images and to
score each image, recording whether the 17 gauge needle was in or out of the epidural space to
determine the accuracy and reliability of this technique.
There was a 97.5%, 95%, and 93.8% agreement between each reviewing physician and the
senior author resulting in a correlation using the Kappa statistic value of 0.950, 0.875, and 0.874,
respectively (P < 0.001). The 3 reviewing physicians disagreed with the senior author’s correct
answer in 2.5%, 5%, and 6.2%, respectively, however, the disagreement occurred primarily
because of poor image quality. Agreement between the 3 reviewing physicians was 93.8%,
96.3%, and 90%, with a Kappa value of 0.875, 0.924, and 0.799, respectively (P < 0.001). There
was 100% technical success in the 278 case series without “wet taps,” provocation of pain during
entry, or any other immediate post procedural complication.
We conclude the CLO view provides an efficient and reliable method to visualize needle tip depth
in relation to the epidural space. The close inter-observer agreement was possible with minimal
physician instruction.
Key words: Cervical interlaminar, cervical epidural, contra-lateral oblique, fluoroscopic imaging
Percutaneous Endoscopic Lumbar Discectomy
for Highly Migrated Lumbar Disc Herniation
Authors: Deng Zhong-Liang
Published: October 2019

Background: Percutaneous endoscopic lumbar discectomy (PELD) has been growing in popularity
for the treatment of lumbar disc herniation (LDH) due to its irreplaceable advantages over
conventional open surgery. Compared with common lumbar disc herniations, discectomy of highly
migrated LDH by PELD is known to be very difficult. Highly migrated lumbar disc herniation has
long been a challenge for its specific characteristics. Three approaches for PELD have been applied
to access a highly migrated LDH, including an interlaminar approach (IL), transforaminal approach
(TF), and contralateral transforaminal approach (CTF). However, none of the existing research has
systematically described the selection of the most appropriate procedure from the 3 approaches or
the individualization of an operative procedure in different cases.
Objectives: The purpose of this study was to present a detailed surgical approach selection and
individualization of procedure in the treatment of highly migrated LDH with PELD. We also mean to
compare the outcomes of patients with highly migrated LDH treated with PELD by the 3 approaches.
Study Design: Single-center retrospective observational study.
Setting: An interventional pain management practice, a medical center, major metropolitan city,
China.
Methods: In our retrospective analysis between March 2011 and March 2013, 73 patients with
single level highly migrated LDH received PELD. Clinical outcomes were assessed with the visual
analogue scale (VAS) score, the modified MacNab criteria, and the Oswestry disability index (ODI).
Relevant data such as operation duration and fluoroscopy frequency of the 3 operative approaches
were recorded.
Results: The mean operating time of IL was 56 minutes, compared with 64 minutes for TF and
112 minutes for CTF. The mean intraoperative fluoroscopy times were 5.5 for IL, 9.7 for TF, and
14.6 for CTF. In each group, the mean VAS and ODI after surgery and 3 months after surgery
improved dramatically compared with preoperative counterparts. However, the difference between
postoperative results and the results 3 months after surgery was not significant (P > 0.05). The
overall excellent rate was 90.4% according to the modified MacNab criteria; there was no significant
statistical difference between the 3 operative routes. Operative complications occurred in 3 patients
(2 after IL and one after CTF, 3 of 73, 4.1%).
Limitations: This study is limited by its sample size.
Conclusion: In our research, PELD with all 3 approaches was similarly effective to highly
migrated disc herniation. The CTF approach required the longest operation duration and the
most intraoperative times. On the contrary, the least operation time and radiographfrequency was
required with the IL approach. In addition, we came to a conclusion of surgery approach selection
when it comes to varied HM-LDH.
Key words: Highly migrated, lumbar disc herniation, percutaneous endoscopic lumbar discectomy,
minimally invasive treatment
Pain Physician 2017;
Cerebral Blood Flow and Heart Rate Variability
in Chronic Fatigue Syndrome: A Randomized
Cross-Over Study
Authors: Malfliet Anneleen
Published: October 2019

Background: Pain, fatigue, and concentration difficulties are typical features of
chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms
are still unknown, but available evidence suggests an important role for impaired pain
modulation. As evidence also suggests that pain modulation is related to cardiovascular
mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart
rate variability (HRV) are altered in these patients.
Objectives: We aimed to investigate the role of the cardiovascular system in pain
modulation and symptoms of CFS; the response of CBF and HRV to physical stress
and their relation to the change in temporal summation (TS) of pressure pain and selfreported symptoms was evaluated.
Study Design: A controlled, randomized cross-over trial.
Setting: University Hospital Brussels.
Methods: Twenty CFS patients and 20 sedentary healthy controls were included in this
study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial
Doppler), and HRV (using finger plethysmography) was examined during physical and
emotional stress (to control for potential bias), as well as their association mutually and
with self-reported symptoms of pain, fatigue, and concentrations difficulties.
Results: There was no significant interaction or group (F-values ranging from .100
to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV
and CBF did change during physical exercise, but the changes did not differ between
patients and controls. While pain scores during TS at the trapezius site reduced in
the control group after the physical exercise protocol (P = .037), they did not change
in the CFS group (P = .108), suggesting impaired pain modulation. There were no
significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values
of correlation analyses > .01).
Limitations: Although effect sizes were medium to large, the study sample was
relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this
mild exercise was able to provoke endogenous pain modulation in the control group,
which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are
more applicable to daily physical activities in CFS patients than vigorous exercises.
Conclusion: These results seem to refute the previously suggested alterations of CBF/
HRV in CFS patients. These cardiovascular parameters appear not to explain pain before,
during, and following exercise.
Key words: Chronic pain, physical exercise, emotional stress, pain modulation,
cardiovascular systems, temporal summation, pain pressure thresholds, transcranial
Doppler, plethysmography
Implication of Two Different Doses of Intradiscal
Ozone-Oxygen Injection upon the Pain
Alleviation in Patients with Low Back Pain: A
Randomized, Single-Blind Study
Authors: Kamel Emad Zarief
Published: October 2019

Background: Low back pain (LBP) is mostly induced by disc herniation (DH) or degeneration
and has a burden upon social activity and economical aspects of life. An abundance of medical
and surgical interventions have evolved to resolve this problem, but one of the newly introduced
techniques, which is the minimally invasive, low cost ozone-oxygen mixture (O3
-O2
) intradiscal
injection, offers a rapid onset amelioration of symptoms with a sustained duration of pain relief.
Objective: We aim to evaluate the quality of pain alleviation using 2 different doses of intradiscal
injections of O3
-O2
mixture.
Study Design: A prospectively randomized, single-blind study.
Setting: Pain clinic, anesthesia, intensive care, and pain department in Assiut University Hospitals.
Methods: Sixty patients with symptomatizing single lumbar DH were subjected to O3
-O2
intradiscal injection and randomly allocated into one of 2 groups; group A: received 10 mL, 40 µg/
mL of O3
-O2
and group B: received 10 mL, 30 µg/mL of O3
-O2
. Pain score and functional ability of
the patients using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated
after 1, 6, and 12 months and compared to the basal values. Patient satisfaction and reduction of
DH were evaluated after the sixth month.
Results: There were no significant differences between the 2 groups regarding the clinical
outcome; however both the ODI and VAS evaluations showed highly significant improvement
(decreased) (P < 0.01) after injection and during the entire follow-up period. There were highly
significant negative correlations between the DH reduction percentage and both the VAS and ODI
scores after 6 months in both of the groups.
Limitations: This study was limited by a small sample size; it was also an active control trial,
which may explain the insignificant difference in between the groups, in addition to being a singleblind trial.
Conclusion: Intradiscal injection of O3
-O2
mixture is a very valuable maneuver in the reduction
of DH size and improvement of pain quality, with either ozone concentrations of 40 µg/mL or 30
µg/mL.
Key words: Low back pain, ozone, disc herniation
Risk Factors for the Occurrence of Insufficient
Cement Distribution in the Fractured Area after
Percutaneous Vertebroplasty in Osteoporotic
Vertebral Compression Fractures
Authors: Jiang Xiaobing
Published: October 2019

Background: Insufficient cement distribution (ICD) in the fractured area has been
advocated to be responsible for unsatisfied pain relief after percutaneous vertebroplasty
(PVP) for osteoporotic vertebral compression fractures (OVCFs). However, little is known
about risk factors for the occurrence of ICD.
Objective: The present study aimed to identify independent risk factors of the
emergence of ICD.
Study Design: A retrospective cohort study.
Setting: Department of spinal surgery, an affiliated hospital of a medical university.
Methods: Patients who underwent PVP for single-level OVCF from January 2012 to
September 2014 and met this study’s inclusion criteria were retrospectively reviewed.
Associations of ICD with co-variates (age, gender, bone mass density with a T-score,
amount of injected cement, cement leakage, fracture level, fracture age, fracture
severity grade, and location of the fractured area) and the influence of ICD on pain relief
were analyzed.
Results: A total of 225 patients were included. ICD was found in 26 (11.6%) patients.
Fractured area located in the superior portion of the index vertebra was significantly
associated with occurrence of ICD. No further significant associations between the
studied co-variates and emergence of ICD were seen in the adjusted analysis. In addition,
patients with ICD had significantly higher immediate postoperative visual analog scale
scores of back pain compared with those with sufficient cement distribution in the
fractured area.
Limitation: Location of the fractured area and cement distribution in the fractured
area could not be evaluated quantitatively.
Conclusions: The incidence of ICD is higher in patients with the fractured area located
in the superior portion of the index vertebra and ICD might be responsible for unsatisfied
pain relief after PVP for OVCFs.
Key words: Percutaneous vertebroplasty, insufficient cement distribution, fractured
area, risk factor, osteoporosis, vertebral compression fracture, spine, unsatisfied pain
relief, cement augmentation
Do Pain Medicine Fellowship Programs Provide
Education in Practice Management? A Survey
of Pain Medicine Fellowship Programs
Authors: Przkora Rene
Published: October 2019

Background: We hypothesized that there is a gap between expectations and actual training in
practice management for pain medicine fellows. Our impression is that many fellowships rely on
residency training to provide exposure to business education. Unfortunately, pain management
and anesthesiology business education are very different, as the practice settings are largely officeversus hospital-based, respectively.
Objective: Because it is unclear whether pain management fellowships are providing practice
management education and, if they do, whether the topics covered match the expectations of their
fellows, we surveyed pain medicine program directors and fellows regarding their expectations and
training in business management.
Study Design: A survey.
Setting: Academic pain medicine fellowship programs.
Methods: After an exemption was obtained from the University of Texas Medical Branch
Institutional Review Board (#13-030), an email survey was sent to members of the Association
of Pain Program Directors to be forwarded to their fellows. Directors were contacted 3 times to
maximize the response rate. The anonymous survey for fellows contained 21 questions (questions
are shown in the results).
Results: Fifty-nine of 84 program directors responded and forwarded the survey to their fellows.
Sixty fellows responded, with 56 answering the survey questions.
Limitations: The responder rate is a limitation, although similar rates have been reported in
similar studies.
Conclusions: The majority of pain medicine fellows receive some practice management training,
mainly on billing documentation and preauthorization processes, while most do not receive
business education (e.g., human resources, contracts, accounting/financial reports). More than
70% of fellows reported that they receive more business education from industry than from their
fellowships, a result that may raise concerns about the independence of our future physicians
from the industry. Our findings support the need for enhanced and structured business education
during pain fellowship.
Key words: Business education, practice management, fellowship training, curriculum
development, knowledge gaps, private practice
Chronic Smoking is Not Associated with
Increased Postoperative Opioid Use in Patients
with Lung Cancer or Esophageal Cancer
Authors: Oh Tak Kyu
Published: October 2019

Background: Chronic smokers show differences in pain sensitivity compared to healthy
non-smokers. Yet, no study to date has examined whether smoker status has an effect on
postoperative pain.
Objective: We aim to examine a possible correlation between preoperative smoking and
postoperative opioid dose based on the hypothesis that smokers would use higher doses of
opioids to manage increased postoperative pain.
Study Design: A retrospective observational cohort study.
Setting: The National Cancer Center in Korea.
Methods: We examined medical record data for patients who had undergone curative
resection for either lung or esophageal cancer (lobectomy or bilobectomy for lung cancer or an
Ivor Lewis operation for esophageal cancer) between January 1, 2006 and December 31, 2010.
We examined the correlation between the total preoperative average number of packs per
day multiplied by years of cigarette smoking (pack-years) and morphine equivalent daily doses
administered to patients after surgery, considering each type of cancer both individually and
together. Partial correlation and regression analyses were performed to determine the causality
of a possible relationship between pack-years of cigarette smoking and postoperative opioid
dose.
Results: A total of 1,129 patients (871 patients with lung cancer and 258 patients with
esophageal cancer) were included in the final analysis. There was no significant correlation
between total pack-years of cigarette smoking and postoperative opioid dose for lung cancer,
esophageal cancer, or both cancer types combined (r = 0.042, -0.012, and 0.037, respectively).
In the analysis of both cancer types combined, video-assisted thoracic surgery (VATS) was
associated with an 11.1% decrease in opioid dose (β = -0.111, P = 0.003) and epidural analgesia
was associated with a 7.2% increase in opioid dose (β = 0.072, P = 0.042).
Limitations: The retrospective design of this study is a limitation.
Conclusion: Our study did not observe a correlation between preoperative smoking and
postoperative opioid dose in patients with lung or esophageal cancer.
Key words: Smoking, postoperative pain, opioid, lung cancer, esophageal cancer, analgesia
Neonatal Sleep Restriction Increases
Nociceptive Sensitivity in Adolescent Mice
Authors: Andersen Monica L
Published: October 2019

Background: Sleep loss in infants may have a negative effect on the functional and structural
development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction
induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs
due to changes in the neuronal activity of nociceptive pathways.
Objectives: We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors
of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and
functional changes in pain pathways associated with behavioral changes.
Study Design: An experimental animal study.
Setting: A basic sleep research laboratory at Universidade Federal de São Paulo in Brazil.
Methods: Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control
(CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2
hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent
sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains
were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex,
primary somatosensory cortex, and periaqueductal gray (PAG).
Results: Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent
mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a
decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The
hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a
comparable nociceptive response.
Limitations: Even using a mild manipulation method, in which a minimal amount of handling
was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher
corticosterone levels.
Conclusion: Repeated exposures to sleep loss during early life were able to induce changes in the
nociceptive response associated with alterations in neural activity in descending control of pain.
Key words: Brain maturation, hypersensitivity, neuronal activity, nociception, pain, periaqueductal
gray, postnatal development, sleep, sleep deprivation
Association of Higher Migraine Risk Among Female
and Younger Chronic Osteomyelitis Patients:
Evidence from a Taiwan Cohort of One Million
Authors: Tseng Chun-Hung
Published: October 2019

Background: Inflammation may trigger migraine development through neurovascular
reactions in the brain. Most of the migraine patients, particularly the younger ones, do not have
any risk factors for this disease. Hence, we assessed whether chronic osteomyelitis (COM), a
chronic inflammatory disease, increases the risk of migraine.
Objective: We aim to evaluate the risk of migraine among female and middle-age COM
patients with a large patient sample.
Study Design: A retrospective cohort study was conducted in this study.
Setting: The data used in this study were extracted from the Taiwan National Health Insurance
(NHI) Research Database.
Methods: A study group with 2,012 COM patients and 8,048 randomly chosen gender- and
age-matched controls were chosen from the Taiwan NHI Research Database (NHIRD) from the
start of 2000 to the end of 2009. The risk of migraine was estimated with Cox proportional
regression model. Both COM and control groups were followed-up until the occurrence of
migraine during the study period (2000–2011). Prevalent covariates, such as age, gender,
hypertension, diabetes, hyperlipidemia, stroke, coronary artery disease, depression, anxiety, sleep
disorder, bipolar disorder, and epilepsy, were included for further evaluation. The hazard ratio
(HR) of migraine was measured with Cox proportional hazard regression model. The primary
outcome was the overall migraine risk among COM patients, and the secondary outcome was
the migraine risk among COM patients lacking the comorbidities. Additional outcomes included
migraine risk among COM patients in different age and gender subgroups.
Results: The overall migraine risk was increased in COM patients (adjusted hazard ratio [aHR]
1.74, 95% confidence interval [CI] 1.14–2.65). Even without any prevalent comorbidities, COM
patients still exhibited an increased risk of migraine (aHR 2.05, 95% CI 1.06–3.97) than the
controls did. Moreover, this risk was relatively higher in COM patients aged < 40 and 45–54
years (aHR 2.07, 95% CI 0.97–4.46 and aHR 2.11, 95% CI 0.97–4.57, respectively) than in their
counterparts. Female COM patients had a relatively higher migraine risk (aHR 1.85, 95% CI
1.05–3.24) than male patients did (aHR 1.68, 95% CI 0.89–3.16).
Limitations: The messages about personal behaviors were unavailable in the Taiwan NHIRD.
Other neurovascular risk factors that might increase migraine cannot be excluded completely in
this research.
Conclusion: An association between COM and increased risk of migraine was shown in this
study. The results suggest that COM is a significant migraine predictor, and thus imply the
necessity for rigorous migraine prevention in COM patients, especially female and younger ones.
Key words: Inflammation, migraine, chronic osteomyelitis, Taiwan National Health Insurance
Research Database
Prevalence and Risk Factors of Neuropathic
Pain in Patients with a Rotator Cuff Tear
Authors: Ko Sangbong
Published: October 2019

Background: Until now, few studies had investigated the neuropathic pain component in
patients with a rotator cuff tear (RCT).
Objectives: The aim of the study was to identify the neuropathic pain component in patients
with RCT and to determine the factors correlated with neuropathic pain in patients with RCT.
Study Design: Prospective, cohort, prognostic study.
Setting: Study patients who required arthroscopic rotator cuff repair were analyzed in a
hospital setting.
Methods: We prospectively studied 101 patients who were less than 60 years old with fullthickness tears requiring arthroscopic rotator cuff repair and met the inclusion and exclusion
criteria. Multiple regression analysis was performed to identify variables that independently
affected neuropathic pain in patients with a RCT. We use Douleur neuropathique 4 questionnaire
(DN4) to assess neuropathic pain, which was ≥ 4 points of the DN4 questionaire. The visual
analog scale (VAS) for the most severe pain within 4 weeks before admission and mean pain
level during the last 4 weeks were checked. The atrophy grades of the rotator cuff muscles were
classified on magnetic resonance images according to the Goutallier classification. The size and
medial retraction of the RCT were measured during arthroscopic repair for RCT.
Results: Sixteen (15.8%) of the 101 patients had neuropathic pain according to the cutoff values on the DN4 questionnaire for diagnosing neuropathic pain. The neuropathic pain
group had significantly higher prevalence of smoking (P = 0.042), more mean VAS during last 4
weeks (P = 0.008), larger cuff tear (P = 0.003), more medial retraction of cuff (P = 0.016), and
severe fatty degeneration of rotator cuff muscles (supraspinatus, P < 0.001; subscapularis, P <
0.001; and infraspinatus, P = 0.003) than the nonneuropathic pain group. The multiple logistic
regression analyses showed that more mean VAS during the last 4 weeks and tear size of a
rotator cuff were independent of other factors for the neuropathic pain of the patients with a
full-thickness RCT.
Limitations: Small sample size is the first limitation of this study.
Conclusions: The prevalence of neuropathic pain in patients with a full-thickness RCT requiring
arthroscopic rotator cuff repair was 15.8 % according to the DN4 questionnaire. The neuropathic
pain component was more relevant to the severity of pain and tear size in the patients with a
full-thickness RCT. It is important to be aware of the existence of neuropathic pain when treating
a patient presenting with pain due to a RCT because accompanying neuropathy with a RCT
could have a worse effect on repair of a RCT.
IRB approval and clinical trial registration number: CR-15-045
Key words: Shoulder, rotator cuff tear, arthroscopic rotator cuff repair, neuropathic pain
Effect of Different Volumes on Pain Relief
in Patient Receiving Fluoroscopic Guided
Interlaminar Lumbar Epidural Steroid Injection
Authors: Makkar Jeetinder Kaur
Published: October 2019

Background: Epidural steroids injections (ESI) are frequently used to treat lumbar radicular
pain. Although different volume have been used for interlaminar ESI in adults, there is no
controlled trial comparing the effect of different volumes on pain relief for the same dose of
steroid .
Objective: To compare the effect of increase in volume of epidural drug on pain relief in
lumbar ESI .
Study design: Randomized double blind trial
Settings: Pain OR of a tertiary care centre
Methods: Sixty patients were randomly allocated to 1 of 3 groups: Group A (4 mL),
Group B (6 mL), and Group C (8 mL). Pain was evaluated using visual analog scale (VAS) and
improvement in disability using modified Oswestry Disability Questionnaire scores (MODQS) at
2, 4, 8, 12, and 24 weeks. Patients having less than 50% pain relief from baseline received an
additional epidural injection of the same volume with a maximum of 3 injections at least 15
days apart. The primary objective of the study was incidence of patients attaining more than
50% pain relief at 6 months. Secondary outcome included MODQS and pattern of spread of
iodinated contrast on fluoroscopy.
Results: At the end of 6 months, there was no significant difference in the effective pain
relief between the 3 groups (Group A-16/22 (72.7%), Group B-15/20 (75%), Group C-13/18
(72.2%); P = 0.98, chi- square test). All groups demonstrated a significant reduction in mean
VAS scores. There was no significant intergroup difference in VAS sores and MODQS at all the
time intervals. The pattern of contrast spread did not differ between the 3 groups.
Limitation: Not a placebo controlled trial
Conclusions: An increase in volume of the injectate from 4 mL to 8 mL did not increase the
efficacy of interlaminar ESI.
Key words: Epidural steroid, volume, low back pain, interlaminar:
Unraveling Self-Reported Signs of Central
Sensitization in Breast Cancer Survivors
with Upper Limb Pain: Prevalence Rate and
Contributing Factors
Authors: Groef An De
Published: October 2019

Background: Hypersensitivity of the central nervous system to environmental and chemical
stimuli is a clinical feature of central sensitization mechanisms that can be assessed with the
central sensitization inventory (CSI).
Objective: The aim was to determine prevalence rate of this feature and explore the
treatment-, patient-, pain-, and psychosocial-related variables associated with the degree of
self-reported signs of central sensitization, assessed with the CSI (0-100), in breast cancer
survivors at long-term.
Study Design: Cross-sectional study.
Setting: University Hospitals, Leuven, Belgium.
Methods: One hundred and forty-six women with persistent pain, more than one year
after breast cancer surgery, were included. The following factors were analyzed by bivariable
and multivariable analysis: 1) treatment-related variables (type of surgery, levels of lymph
node dissected, radiotherapy, chemotherapy, hormone therapy, and trastuzumab); 2) patient’s
related variables (age and body mass index); 3) pain-related variables (pain intensity, pain
quality, primary hyperalgesia, and index of widespread pain); and 4) psychosocial variables
(the degree of pain catastrophizing and vigilance and awareness to pain). The dependent
variable was degree of central sensitization measured with the CSI. Additionally, a stepwise
regression was performed.
Results: Fifty-five (38%) patients reported signs of central sensitization measured with the
CSI (i.e., > 40/100). From multivariable analysis, it appears that more severe pain quality and
higher levels of pain catastrophizing contribute to a higher degree of central sensitization.
The stepwise regression revealed that up to 24% of variance of the CSI can be explained by
these factors.
Limitations: A selection bias may be present since patients were all recruited from a larger
cohort participating in clinical trials on the effectiveness of physical therapy after breast cancer
treatment.
Conclusion: Signs of central sensitization cannot be neglected in breast cancer survivors at
long term. More severe pain quality and pain catastrophizing contribute to higher levels of
central sensitization in this population.
Key words
Reframing the Prevention Strategies of the
Opioid Crisis: Focusing on Prescription Opioids,
Fentanyl, and Heroin Epidemic
Authors: Manchikanti Laxmaiah
Published: October 2019

The opioid epidemic has been called the “most consequential preventable public health problem
in the United States.” Though there is wide recognition of the role of prescription opioids in the
epidemic, evidence has shown that heroin and synthetic opioids contribute to the majority of
opioid overdose deaths. It is essential to reframe the preventive strategies in place against the
opioid crisis with attention to factors surrounding the illicit use of fentanyl and heroin.
Data on opioid overdose deaths shows 42,000 deaths in 2016. Of these, synthetic opioids other
than methadone were responsible for over 20,000, heroin for over 15,000, and natural and semisynthetic opioids other than methadone responsible for over 14,000. Fentanyl deaths increased
520% from 2009 to 2016 (increased by 87.7% annually between 2013 and 2016), and heroin
deaths increased 533% from 2000 to 2016. Prescription opioid deaths increased by 18% overall
between 2009 and 2016.
The Drug Enforcement Administration (DEA) mandated reductions in opioid production by 25%
in 2017 and 20% in 2018. The number of prescriptions for opioids declined significantly from
252 million in 2013 to 196 million in 2017 (9% annual decline over this period), falling below the
number of prescriptions in 2006. In addition, data from 2017 shows significant reductions in the
milligram equivalence of morphine by 12.2% and in the number of patients receiving high dose
opioids by 16.1%.
This manuscript describes the escalation of opioid use in the United States, discussing the roles
played by drug manufacturers and distributors, liberalization by the DEA, the Food and Drug
Administration (FDA), licensure boards and legislatures, poor science, and misuse of evidencebased medicine. Moreover, we describe how the influence of pharma, improper advocacy by
physician groups, and the promotion of literature considered peer-reviewed led to the explosive
use of illicit drugs arising from the issues surrounding prescription opioids.
This manuscript describes a 3-tier approach presented to Congress. Tier 1 includes an aggressive
education campaign geared toward the public, physicians, and patients. Tier 2 includes facilitation
of easier access to non-opioid techniques and the establishment of a National All Schedules
Prescription Electronic Reporting Act (NASPER). Finally, Tier 3 focuses on making buprenorphine
more available for chronic pain management as well as for medication-assisted treatment.
Key words: Opioid epidemic, fentanyl and heroin epidemic, prescription opioids, National All
Schedules Prescription Electronic Reporting Act (NASPER), Prescription Drug Monitoring Programs
(PDMPs)
Is Unilateral Percutaneous Kyphoplasty Superior
to Bilateral Percutaneous Kyphoplasty for
Osteoporotic Vertebral Compression Fractures?
Evidence from a Systematic Review of Discordant
Meta-Analyses
Authors: Cai Dongling
Published: October 2019

Background: Several meta-analyses have been performed to compare unilateral percutaneous
kyphoplasty (PKP) and bilateral PKP in the treatment of osteoporotic vertebral compression
fractures (OVCFs), but inconsistencies in the results have led to questions as to which technique
is preferable.
Objective: This study was designed to clarify the benefits and disadvantages of unilateral PKP
versus bilateral PKP as found in numerous discordant meta-analyses and thereby present surgical
treatment recommendations for OVCFs considering the current best evidence.
Study Design: Systematic review/Meta-analysis.
Methods: Meta-analyses on unilateral and bilateral PKP for OVCFs were included by searching
Pubmed, Embase, and Cochrane library. Meta-analysis quality was assessed using Oxford Levels of
Evidence and Assessment of Multiple Systematic Reviews (AMSTAR). The Jadad decision algorithm
was used to identify the best evidence.
Results: Eight eligible meta-analyses were included, 7 of which were Level-II evidence and one was
Level-III evidence. The AMSTAR scores varied from 7 to 8. The Jadad decision algorithm suggested
that the best meta-analysis should be selected depending upon publication characteristics and
methodology of primary studies, language restrictions, and whether data analysis was performed
on individual patients. The best available evidence indicated that both unilateral and bilateral PKP
could receive similar good clinical and radiological outcomes. However, without increasing the risk
of complications, unilateral PKP required shorter surgical time and less cement volume, offering
better pain relief and quality of life at post-operative short term follow-ups.
Limitations: Primary studies had defects in their methodologies.
Conclusions: Unilateral PKP appears to be superior to bilateral PKP in the treatment of OVCFs.
Key words: Osteoporotic vertebral compression fractures, percutaneous kyphoplasty,
meta-analysis