bluuebunny/crossref_metadata_2025 huggingface dataset:
Down-Regulation of Insulin Signaling Is
Involved in Painful Diabetic Neuropathy in
Type 2 Diabetes
Authors: Li Yun-Qing
Published: February 2021

Background: Previous theories considered that the main cause of painful diabetic neuropathy
(PDN) was due to hyperglycemia. However, recent evidence indicated that hyperinsulinemia plays
a greater role in type 2 diabetic metabolisms (T2DM).
Objectives: Our aim was to explore insulin signaling to determine the molecular mechanism
involved in the pathogenesis of PDN in T2DM.
Study Design: A randomized, double blind, controlled animal trial.
Methods: We observed the localization of insulin receptor (IR) and phosphorylated insulin
receptor substrate 1 (IRS-1) in the spinal cord using in situ hybridization and immunohistochemistry.
Then we investigated the alternations of IR and pIRS-1 and the activity of the JAK2/STAT3 pathway
by immunohistochemistry, Western Blotting, and cell culture. Finally, we detected the influence of
intrathecal JAK2/STAT3 inhibitor (AG490) on nociceptive behavior and insulin signaling in ob/ob
mice using Western Blotting.
Results: We found that IR and pIRS-1 are mainly located in neurons in the superficial layer of
the spinal dorsal horn. The expressions of IR and pIRS-1 decreased and the JAK2/STAT3 pathway
activated in the spinal dorsal horn in ob/ob mice with mechanical hyperalgesia. Next, our in vitro
results indicated that hyperinsulinemia and hyperglycemia impaired insulin signaling along with
the activated JAK2/STAT3 pathway in differentiated human neuronal cells (SH-SY5Y). Treatment
through intrathecal injection of AG490, an inhibitor of the JAK2/STAT3 pathway, alleviated
mechanical hyperalgesia in ob/ob mice and prevented impaired insulin signaling in the spinal cord.
Limitations: The activation of the JAK2/STAT3 pathway could not explain the mechanism of
PDN in T1DM.
Conclusions: We demonstrate that insulin signaling impairment in the spinal dorsal horn is
associated with the activated JAK2/STAT3 pathway, which contributes to the progressive PDN in
T2DM.
Key words: Painful diabetic neuropathy, mouse, insulin receptor, insulin receptor substance 1,
JAK2, STAT3
Effect of Two Contrasting Interventions on
Upper Limb Chronic Pain and Disability: A
Randomized Controlled Trial
Authors: Sundstrup Emil
Published: February 2021

Background: Chronic pain and disability of the arm, shoulder, and hand severely affect labor
market participation. Ergonomic training and education is the default strategy to reduce physical
exposure and thereby prevent aggravation of pain. An alternative strategy could be to increase
physical capacity of the worker by physical conditioning.
Objectives: To investigate the effect of 2 contrasting interventions, conventional ergonomic
training (usual care) versus resistance training, on pain and disability in individuals with upper limb
chronic pain exposed to highly repetitive and forceful manual work.
Study Design: Examiner-blinded, parallel-group randomized controlled trial with allocation
concealment.
Setting: Slaughterhouses located in Denmark, Europe.
Methods: Sixty-six adults with chronic pain in the shoulder, elbow/forearm, or hand/wrist and
work disability were randomly allocated to 10 weeks of specific resistance training for the shoulder,
arm, and hand muscles for 3 x 10 minutes per week, or ergonomic training and education (usual
care control group). Pain intensity (average of shoulder, arm, and hand, scale 0 – 10) was the
primary outcome, and disability (Work module of DASH questionnaire) as well as isometric shoulder
and wrist muscle strength were secondary outcomes.
Results: Pain intensity, disability, and muscle strength improved more following resistance training
than usual care (P < 0.001, P = 0.05, P < 0.0001, respectively). Pain intensity decreased by 1.5
points (95% confidence interval -2.0 to -0.9) following resistance training compared with usual
care, corresponding to an effect size of 0.91 (Cohen’s d).
Limitations: Blinding of participants is not possible in behavioral interventions. However, at
baseline outcome expectations of the 2 interventions were similar.
Conclusion: Resistance training at the workplace results in clinical relevant improvements in
pain, disability, and muscle strength in adults with upper limb chronic pain exposed to highly
repetitive and forceful manual work.
Trial registration: NCT01671267.
Key words: Musculoskeletal pain, workability, shoulder pain, elbow pain, tennis elbow, wrist
pain
A Pressure Comparison Between Midline
and Paramedian Approaches to the Cervical
Epidural Space
Authors: Moon Jee Youn
Published: February 2021

Background: In the cervical spine, the ligamentum flavum (LF) is often incompletely fused
at the midline. Therefore, accessing the epidural space (ES) using the loss of resistance (LOR)
technique via the midline approach could be less reliable than the paramedian approach. Since
the tactile sensation of LOR is due to abrupt loss of pressure upon entering the ES, we have
compared pressure changes between the 2 different cervical epidural techniques.
Objectives: The aim of this study was to compare pressure changes during the pathway to
the cervical ES between the 2 approaches.
Study Design: A prospective, open-labeled, randomized, comparative study.
Setting: An interventional pain management practice in a hospital, Republic of Korea.
Methods: The 74 patients were randomly assigned to either a midline or paramedian group.
The pressure changes were monitored and classified into 4 grades according to the following
criteria:
Grade I. The pressure waveform sequence consisted of 3 components in chronological order:
1) a high positive pressure just prior to entering the ES; 2) an abrupt pressure decrease at the
moment of entering the ES; and 3) a negative peak pressure before cervical epidural pressure
equilibration. Grade II. A high positive pressure followed by a precipitous pressure drop,
without negative peak pressure upon entering the ES. Grade III. High positive pressure before
entering the ES, followed by continuous pressure decrease without negative pressure. Grade
IV. No pressure changes before or after entering the cervical ES.
Results: An abrupt pressure decrease at the moment of exiting the LF or entering the ES was
more frequently observed when using the paramedian approach (P < 0.05) with the odds ratio
of 4.96 (95% CI, 1.63 – 15.12) as compared with the midline approach.
Limitations: A correlation between the abrupt pressure decrease and LOR tactile sensation
has been assumed.
Conclusion: Under the assumption that the LOR sensation is due to an abrupt decrease in
pressure the moment the needle enters the ES or exits the LF, this study claims that the accuracy
of accessing the cervical ES can be improved significantly using the paramedian approach.
Clinical trial: NCT01009385. Institutional Review Board (IRB): H-1208-107-422
Key words: Cervical epidural injection, loss of resistance technique, ligamentum flavum,
midline approach, paramedian approach, epidural space
High Dose Intrathecal Morphine for Major
Abdominal Cancer Surgery: A Prospective
Double-Blind, Dose-Finding Clinical Study
Authors: Abdel-Ghaffar Hala S.
Published: February 2021

Background: Despite 30 years of clinical research, we still do not know the optimal
dose of intrathecal morphine (ITM) when used alone.
Objectives: A safety investigation and comparison of the analgesic efficacy of ITM 0.2 mg, 0.5
mg, and 1 mg in patients undergoing major abdominal cancer surgery.
Study Design: A randomized, double-blind trial.
Setting: Academic medical center.
Methods: Ninety patients were randomly assigned to receive morphine intrathecally either 0.2
mg (Group I, ITM 0.2 mg, n = 30), 0.5 mg (Group II, ITM 0.5 mg, n = 30), or 1 mg (Group III,
ITM 1 mg, n = 30) dissolved in 5 mL physiological saline before general anesthesia. Assessment
parameters included hemodynamics, respiratory rate, peripheral arterial oxygenation, sedation
score, pain severity, time of first analgesic request, total analgesic consumption, and side effects
in the first 72 hours.
Results: The mean time to first request for rescue analgesia was significantly prolonged in Group
II (22.13 ± 5.21 hours, P < 0.001) and Group III (30.83 ± 4.89 h, P < 0.001), compared with Group
I (0.50 ± 0.66 hours). The mean tramadol consumption dose was significantly reduced in Group
II (383.33 ± 91.28 mg, P < 0.001) and Group III (300 ± 69.48 mg, P < 0.001) compared with
Group I (770 ± 114.92 mg). Patients received 1 mg ITM showed lower VAS scores in the first 48
h postoperative (P < 0.04) compared with Group I and Group II. No significant differences were
observed in the mean systolic and diastolic blood pressure values, respiratory rate, and peripheral
arterial oxygen saturation between groups. Lower mean heart rate values were observed in Group
III patients at 6 hours (P < 0.01) and 12 hours (P < 0.03) postoperative compared with Group I
and Group II patients. Six patients (20%) in Group II and 8 (26.7%) in Group III exhibited pruritus
compared with 2 patients (6.66%) in Group I (P < 0.01). No intergroup statistical differences were
observed for other studied side effects.
Limitations: This study is limited by its small sample size.
Conclusion: One mg ITM provided superior analgesia for 48 hours postoperative compared with
0.2 mg and 0.5 mg ITM with a nonsignificant difference in the incidence of side effects. Further
studies of larger sample size are recommended to confirm these findings.
Key words: Anesthesia, analgesia, abdominal cancer, opioids, intrathecal, morphine
Chronic Opioid Therapy for Chronic Non-Cancer
Pain: A Review and Comparison of Treatment
Guidelines
Authors: Cheung Chi-Wai
Published: February 2021

Background: Long-term opioid use for chronic non-cancer pain has increased substantially
in recent years despite the paucity of strong supporting scientific data and concerns regarding
adverse effects and potential misuse.
Study Design: Review and summary of practice guidelines available on PubMed and
Cochrane databases as well as on the Internet on chronic opioid therapy from June 2004 to
June 2013.
Objective: To review expert-developed practice guidelines on chronic opioid therapy, published
in different countries over the past decade in order to reveal similar principles of therapy and
to provide useful information and references for future development of opioid guidelines to
identify adequately supported practice points and areas in need of further scientific evidence.
Method: Seven guidelines were identified as pertaining specifically to the long-term use of
opioids for general chronic non-cancer pain from an initial search of the PubMed/Medline
and Cochrane databases using combinations of the search terms “opioid,” “chronic opioid
therapy,” “chronic pain,” “chronic non-cancer pain,” “chronic non-malignant pain,”
“guidelines,” “practice guidelines,” and “clinical practice guidelines,” filtered to include only
articles on humans published in the English language over the past 10 years.
Results: All guidelines espouse an individual approach to management, beginning with a
comprehensive patient evaluation, with particular focus on eliciting factors that may indicate
potential drug misuse and abuse, and a trial of therapy to determine the course of treatment.
Goals of treatment should be adequately discussed with and consented to by the patient.
Opioids are generally not recommended as first-line therapy but, when used, clinicians should
closely monitor patients for loss of response, adverse effects or aberrant behavior, and revise
the treatment plan accordingly. Urine drug testing (UDT) may be used as a tool to monitor for
aberrant behavior or drug misuse; opioid rotation may be considered when loss of response or
adverse effects are a concern, at a starting dose lower than the calculated equianalgesic dose.
Limitations: Information on some African nations, countries in the Middle-East, and Pacific
Islands is not available and therefore was not included in this review.
Conclusion: There is a growing body of scientific evidence to support opioid use in chronic
pain. Future work should focus on continuing to generate good-quality evidence on the longterm benefits of opioid therapy, as well as scientific data to guide drug choice and dosing for
specific conditions, populations, and situations.
Key words: Chronic pain, opioid, non-cancer pain, guidelines, opioid rotation, pain
management, opioid therapy
Applying Modern Pain Neuroscience in Clinical
Practice: Criteria for the Classification of
Central Sensitization Pain
Authors: Nijs Jo
Published: February 2021

Background: The awareness is growing that central sensitization is of prime
importance for the assessment and management of chronic pain, but its classification
is challenging clinically since no gold standard method of assessment exists.
Objectives: Designing the first set of classification criteria for the classification of
central sensitization pain.
Methods: A body of evidence from original research papers was used by 18 pain
experts from 7 different countries to design the first classification criteria for central
sensitization pain.
Results: It is proposed that the classification of central sensitization pain entails 2 major
steps: the exclusion of neuropathic pain and the differential classification of nociceptive
versus central sensitization pain. For the former, the International Association for the
Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic
pain. For the latter, clinicians are advised to screen their patients for 3 major classification
criteria, and use them to complete the classification algorithm for each individual
patient with chronic pain. The first and obligatory criterion entails disproportionate
pain, implying that the severity of pain and related reported or perceived disability are
disproportionate to the nature and extent of injury or pathology (i.e., tissue damage
or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain
distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to
the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization
Inventory).
Limitations: Although based on direct and indirect research findings, the classification
algorithm requires experimental testing in future studies.
Conclusion: Clinicians can use the proposed classification algorithm for differentiating
neuropathic, nociceptive, and central sensitization pain.
Key words: Chronic pain, diagnosis, hypersensitivity, classification, neuropathic pain
Efficacy and Safety of Dexmedetomidine
Added to Caudal Bupivacaine in Pediatric Major
Abdominal Cancer Surger
Authors: Othman Ahmed H.
Published: February 2021

Background: Caudal analgesia has been prolonged by the addition of various adjuvants.
Dexmedetomidine is a highly selective α2agonist with sedative and analgesic properties.
Objective: To investigate the effect of addition of dexmedetomidine to 0.25% bupivacaine for
caudal analgesia in children undergoing major abdominal cancer surgery.
Study Design: A randomized double-blind trial.
Setting: Academic medical center.
Methods: Forty pediatric patients, aged 3 – 12 years, weighting 10 – 40 kg, and of American
Society of Anesthesiologists (ASA) physical status I and II scheduled for major abdominal cancer
surgeries under general anesthesia combined with caudal analgesia were enrolled. They were
randomly allocated into 2 groups: Group I (BD): (n = 20) received 1 mL/kg bupivacaine 0.25% with
dexmedetomidine 1 µg/kg and group II (B): (n = 20) received 1 mL/kg bupivacaine 0.25%. Heart rate
(HR), mean arterial pressure (MAP), and oxygen saturation (SPO2) were recorded for 120 minutes.
Pain was assessed immediately postoperative and at hours 2, 4, 6, 12, 18, and 24 of postoperative
period by Face, Legs, Activity, Cry and Consolability (FLACC) score. Time to first request for analgesia
and total analgesic consumption [Intravenous acetaminophen 15mg/kg (perfalgan, Squibb)] in the
first 24 hours were recorded. The level of sedation was recorded using Ramsay’s sedation scale.
Adverse effects were recorded and treated.
Results: There was significant reduction in FLACC score in group BD at 2, 4, 6, and 12 hours
postoperatively compared to group B. At the eighteenth and twenty-fourth hour there was no
significant difference. Time of the first rescue analgesic requirement was significantly prolonged in
group BD compared to group B. The mean total consumption of rescue analgesia in the 24 hours
of the postoperative period was significantly decreased in group BD (405.00 ± 215.03) mg when
compared with group B (810.35 ± 200.93) mg.
Limitations: This study is limited by its small sample size.
Conclusion: Addition of dexmedetomidine (1 µg/kg) to caudal bupivacaine 0.25% (1 mL/kg) in
pediatric major abdominal cancer surgeries achieved significant postoperative pain relief for up to
19 hours, with less use of postoperative analgesics, and prolonged duration of arousable sedation.
Hemodynamic changes were statistically significant, yet of no clinical significance.
Key words: Dexmedetomidine, caudal block, pediatric cancer surgery
Medication Compliance in Patients with
Chronic Pain
Authors: Schwarzer Andreas
Published: February 2021

Background: Despite hints about the high incidence of pain patients misreporting their pain
medication use, there are only a few non-controlled studies on the topic that focus solely on
opioids.
Objective: Using toxicological analyses in a cross-sectional study, we investigated patients’
reliability regarding their report of any current pain medication use.
Study Design: A cross-sectional study.
Setting: A comprehensive pain center and a surgical unit of a German University Hospital.
Methods: Consecutive outpatients at their first visit to the pain clinic (PG, n = 243) and pre-surgical
control patients (SG, n = 100) suffering from pain reported on their current pain medication. The
patients’ reports were verified in serum and urine using specific toxicological methods. Two types
of noncompliance were defined: under-reporting (detection of non-reported substances) and overreporting (reported substances undetectable). The impact of clinical parameters on compliance was
investigated using binary logistic regression.
Results: The incidence of noncompliance was significantly higher in the PG (43.3%) than in
the SG (24%; P < 0.05). Under-reporting occurred similarly in both groups (31% PG; 23% SG),
whereas over-reporting predominantly appeared in the PG (11% vs. 2%; P < 0.05). Opioids were
not most frequently under-reported, but the highest proportion of under-reported drugs (underreported in relation to detection incidence) was found for non-opioid analgesics (NSAIDs: 29% PG;
25% SG; other: 42% PG; 32% SG) and psychotropic drugs (35% PG; 53% SG). In the PG, logistic
regression revealed high depression scores to be predictive for noncompliance (odds ratio 2.12).
Limitations: Due to lack of a structured follow-up interview motives of under- and over-reporting
stay speculative.
Conclusions: Under-reporting of non-opioid analgesics is the main type of noncompliance, a
disquieting fact in light of their toxicity and adverse effects. Further research is required in terms
of drug assessment and compliance improvement strategies in pain clinics; therefore, toxicological
monitoring is indispensable.
Clinical Trial: NCT01625065; Medi-3889-10
Key words: Medication compliance, adherence, chronic pain, toxicological analyses, urine drug
testing, NSAID, opioids
Prevalence of Chronic Pelvic Pain Among
Women: An Updated Review
Authors: Ahangari Alebtekin
Published: February 2021

Background: Chronic pelvic pain (CPP), defined as a noncyclical pain lasting for more than 6
months can lead to lower physical performance and quality of life in women. CPP is a worldwide
problem affecting women of all ages. However, health care professionals and researchers, due to
its complex nature and the lack of knowledge surrounding the condition, frequently neglect CPP.
Subsequently, basic data and knowledge regarding CPP remain incomplete.
Objective: To update the review of the worldwide estimation of the CPP prevalence considering
the World Health Organization systematic review by Latthe et al in 2006 as point of departure.
Study Design: A systematic review of CPP prevalence studies.
Method: Electronic search was performed to find related articles through PubMed between 2005
and 2012 based on the PRISMA statement (2009).
Results: From 140 studies, only 7 studies were about CPP prevalence. Their study design consisted
of 3 cross sectional studies, one population based mailing questionnaire study, one survey study
(computer assisted telephone interview), one data analysis by questionnaire, and one prospective
community based study.
Limitations: Paucity of population based studies in addition to probability of existence of studies
at the local level with limited access to worldwide databases, lack of consensus about definition of
CPP among researchers and therapists, and non-inclusion of CPP related key words in databases
such as PubMed.
Conclusion: Based on these articles, prevalence in general ranged between 5.7% and 26.6%.
There were many countries and regions without basic data in the field of CPP. This review shows
the paucity of studies, especially multidisciplinary researches with multifactorial views on CPP.
Multidisciplinary studies would provide more reliable data for estimating the prevalence of CPP and
its psycho-socioeconomic burden, as well as finding its etiologies and characteristics. This would be
the first step towards better treatment and care for women with CPP.
Key words: Chronic pelvic pain, women, epidemiology, prevalence, human, female
Case Series on Variable Presentation of
Ligamentum Flavum Stimulation Following
Percutaneous Cylindrical Spinal Cord Stimulator
Lead Implants
Authors: Jang Dr. Susie S
Published: February 2021

Background: Stimulation-evoked discomfort secondary to ligamentum flavum
stimulation (LFS) is a technological limitation of percutaneous spinal cord stimulator (SCS)
lead implants. There is a paucity of literature describing the clinical presentation and time
periods at which this side effect may present following insertion of cylindrical lead(s).
Objective: To describe a series of 5 patients who presented at varying time periods after
SCS lead placement with LFS.
Study Design: Retrospective case series.
Methods: We performed a chart review of online medical records of patients with
symptoms consistent with LFS at an academic interventional pain clinic identified over 7
consecutive years (2006 - 2013).
Results: LFS most frequently presented within months of implantation of cylindrical leads.
One patient complained of LFS during the temporary trial while another developed LFS
after lead revision. All patients were successfully treated when paddle electrodes replaced
percutaneous cylindrical leads.
Conclusion: LFS may present as a barrier to successful SCS treatment. Clinicians placing
percutaneous SCS leads should be aware of the variable time course of LFS presentation.
Paddle style electrodes seem to offer an enduring solution to LFS so that patients may
continue to benefit from SCS therapy.
Key words: Percutaneous electrodes, cylindrical electrode, paddle electrodes, ligamentum
flavum stimulation, unwanted stimulation
Lumbar Subarachnoid Hematoma Following an
Epidural Blood Patch for Meningeal Puncture
Headache Related to the Implantation of an
Intrathecal Drug Delivery System
Authors: Koyyalagunta Dhanalakshmi
Published: February 2021

Persistent meningeal puncture headache (MPH) is a known complication following
both intentional and unintentional puncture of the dura mater. We present a case of
persistent MPH following implantation of an intrathecal drug delivery system (IDDS).
Two separate epidural blood patches (EBP) were performed under radiographic
guidance with contrast visualization of the epidural space on postoperative days
16 and 28, respectively. The case was complicated by the development of a
symptomatic lumbar subarachnoid hematoma diagnosed on postoperative day 35.
The patient subsequently underwent a laminectomy, evacuation of the hematoma,
and explanation of the IDDS. This case illustrates a potential unique morbidity
associated with the EBP in a patient with an IDDS. The report concludes with a
brief review of MPH followed by a discussion of possible mechanisms underlying
this complication.
Key words: Epidural blood patch, post dural puncture headache, meningeal
puncture headache, complications, spinal subarachnoid hematoma, intrathecal
drug delivery, implantable pain therapies, ziconotide, tinnitus, pain, pain procedures
Human Umbilical Cord Mesenchymal Stem Cell
Transplantation for the Treatment of Chronic
Discogenic Low Back Pain
Authors: Peng Baogan
Published: February 2021

Background: Chronic low back pain is one of the major causes of disability and thus has a
major socioeconomic impact. Intervertebral disc degeneration is the main cause of chronic low
back pain. Treatment for chronic discogenic low back pain has traditionally been limited to either
conservative management or surgical fusion. If conservative treatment fails, then surgical fusion
is commonly considered. Current treatments are limited to treat the symptoms and not the
underlying biologic alterations of the disc.
Objective: Human umbilical cord tissue-derived mesenchymal stem cells (HUC-MSCs) contain
stem cells and possess the ability to regenerate degenerative discs. Based on the results of previous
in vitro and animal experiments, we conducted a preliminary study to test the feasibility and safety
and to obtain an early indication for the therapeutic value of HUC-MSC transplantation in patients
with chronic discogenic low back pain.
Study Design: This is the first study involving treatment of chronic low back pain using HUCMSC transplantation.
Setting: The study was performed at a spine center in China.
Methods: Two patients with chronic discogenic low back pain were treated with HUC-MSC
transplantation. An 11-point visual analog scale (VAS, 0 – 10) and Oswestry Disability Index (ODI,
0 – 100) were used to assess the back pain symptoms and the lumbar function, respectively.
Results: After transplantation, the pain and function improved immediately in the 2 patients.
The VAS and ODI scores decreased obviously during a 2-year follow-up period.
Limitations: The shortcoming of this study is that it is a preliminary study with only 2 patients.
Conclusion: The clinical outcomes indicated that HUC-MSC transplantation is a favorable
alternative method for the treatment of chronic discogenic low back pain.
Key words: Intervertebral disc degeneration, discogenic low back pain, chronic low back pain,
lumbar discography, mesenchymal stem cells, human umbilical cord mesenchymal stem cells,
transplantation
High Cervical Epidural Neurostimulation for
Post-Traumatic Headache Management
Authors: Elahi Foad
Published: February 2021

Headache following head injuries has been reported for centuries. The majority of post-traumatic
headache (PTH) patients will report resolution of their complaints within a few months from the
time of the initial injury. PTHs can contribute to disability, lost productivity, and health care costs.
In this article we discuss a 40-year-old male with a history of motor vehicle accident and basal
skull fracture. The patient had no headache history prior to the accident. He presented with
more than 3 years persistent daily headache. The patient described constant throbbing and
stabbing quality headaches predominantly on the left hemicranium with constant facial pain.
He denies having aura, nausea, or vomiting, but reported occasional neck tightness.
An extensive workup was carried out under the direction of the patient’s primary neurologist.
Secondary to persistent intractable pain, the patient was referred to the pain clinic for further
evaluation. As his headaches were resistant to all trialed strategies, we decided to turn our
therapeutic focus toward electrical neuromodulation along with continuing multimodal
medications and multidisciplinary approach. During 7 days of high cervical dorsal column
electrical nerve stimulation trial, he reported almost 90% pain reduction and significant
improvement on his quality of life. On 12 months follow-up after he underwent a permanent
implant of high cervical dorsal column electrical nerve stimulation, he reported the same level
of pain reduction along with 100% satisfaction rate.
To the best of our knowledge, there have been no publications to date concerning the
application of high cervical nerve stimulation for PTH.
Key words: Post-traumatic headache, migraine headache, cluster headache, electrical
neurostimulation, neuromodulation, trigeminocervical complex, high cervical spinal cord
stimulation
Local Anesthetic Sympathectomy Restores fMRI
Cortical Maps in CRPS I after Upper Extremity
Stellate Blockade: A Prospective Case Study
Authors: Enax-Krumova Dr. Elena K.
Published: February 2021

Background: Patients with complex regional pain syndrome type I (CRPS I) show a cortical
reorganization with contralateral shrinkage of cortical maps in S1. The relevance of pain and
disuse for the development and the maintenance of this shrinkage is unclear.
Objective: Aim of the study was to assess whether short-term pain relief induces changes in
the cortical representation of the affected hand in patients with CRPS type I.
Study Design: Case series analysis of prospectively collected data.
Methods: We enrolled a case series of 5 consecutive patients with CRPS type I (disease duration
3 – 36 months) of the non-dominant upper-limb and previously diagnosed sympathetically
maintained pain (SMP) by reduction of the pain intensity of more than > 30% after prior
diagnostic sympathetic block. We performed fMRI for analysis of the cortical representation of
the affected hand immediately before as well as one hour after isolated sympathetic block of the
stellate ganglion on the affected side. Statistics: Wilcoxon-Test, paired t-test, P < 0.05.
Results: Pain decrease after isolated sympathetic block (pain intensity on the numerical rating
scale (0 – 10) before block: 6.8 ± 1.9, afterwards: 3.8 ± 1.3) was accompanied by an increase in
the blood oxygenation level dependent (BOLD) response of cortical representational maps only
of the affected hand which had been reduced before the block, despite the fact that clinical and
neurophysiological assessment revealed no changes in the sensorimotor function.
Limitations: The interpretation of the present results is partly limited due to the small number
of included patients and the missing control group with placebo injection.
Conclusions: The association between recovery of the cortical representation and pain relief
supports the hypothesis that pain could be a relevant factor for changes of somatosensory
cortical maps in CRPS, and that these are rapidly reversible.
Key words: Cortical reorganization, cortical plasticity, cortical maps, complex regional pain
syndrome (CRPS), sympathetically maintained pain (SMP), sympathetic block (SB)
Neurolytic Transversus Abdominal Plane Block
with Alcohol for Long-Term Malignancy Related
Pain Control
Authors: Hung Joseph C.
Published: February 2021

There have been several case reports in the literature of neurolytic transversus
abdominis plane (TAP) blocks being used for malignant abdominal wall pain. However,
most used phenol as a neurolytic agent. We found only a single case report by
Sakamoto using alcohol for TAP neurolysis. Unfortunately this patient passed away
only 5 days after performance of the block. We attempt to extend upon the existing
literature by describing neurolytic TAP blockade outcomes using alcohol on 3 cancer
patients with metastatic disease to the abdominal wall. Two of our 3 patients had
colorectal cancer invading the abdominal musculature. The third patient had a
metastatic neuroendocrine nodule in the left rectus muscle. In our case series, all 3
patients had sustained and significant (greater than 50%) relief of abdominal wall pain
after performing TAP neurolysis using alcohol. Ultrasound guidance was used for all
blocks. The concentration of alcohol used varied from 33% to 77% between patients.
Duration of relief lasted between 17 days and 6 months. Opioid use either decreased
or remained relatively stable for prolonged periods of time after neurolysis. Other than
one patient with transient post-procedure pain related to alcohol injection, there were
no significant complications. Addition of a depo steroid for diagnostic TAP blockade
prior to neurolysis did not appear to extend or provide additional analgesia. Based on
our observations, TAP neurolysis using alcohol also offers a feasible option for longterm control of malignant abdominal wall pain. Further investigation is needed to
determine if alcohol offers any significant advantage compared with phenol.
Key words: Transversus abdominis plane block, TAP Block, cancer pain, neurolysis,
alcohol, ultrasound, abdominal pain, interventional pain management
The Incidence and Risk Factors for Lumbar or
Sciatic Scoliosis in Lumbar Disc Herniation and
the Outcomes after Percutaneous Endoscopic
Discectomy
Authors: Kim Chi Heon
Published: February 2021

Background: Some patients with lumbar herniated intervertebral disc disease (HIVD) suffer
from both pain and lateral shift or trunk list. In addition to pain, patients have concerns
regarding whether trunk list is reversible. Surgical treatment is performed when pain is
intractable to conservative management, but a reversal of trunk list is an incidental outcome.
Percutaneous lumbar endoscopic discectomy (PELD) is one of the surgical treatment options
for lumbar HIVD, but no results concerning its effect on trunk list have been reported.
Objectives: The objectives of the present study were to determine the incidence of, and
risk factors for, trunk list scoliosis or lateral shift and to report the outcomes of trunk list after
PELD.
Study Design: Retrospective case study. IRB No. H 1111-025-384
Setting; University medical Center, Seoul, Korea.
Methods: We selected 164 patients who were less than 60 years old, complained of
unilateral leg pain, and underwent PELD. We measured the maximum trunk shift from the
central sacral vertical line (CSVL-max) on preoperative whole spine radiographs and classified
trunk list as CSVL-max ≥ 10 mm. CSVL-max was measured on serial radiographs taken at one,
3, 6, and 12 months postoperatively in patients with trunk list.
Results: Twenty-nine patients (17.9%) had trunk list (M:F=10:19; mean age, 37.1 ± 11.24
years). Female gender (OR 4.28; 95% CI, 1.49 – 12.3) and HIVD at L4-5 (OR 5.6; 95% CI,
1.8 - 16.7) were risk factors for trunk list. Trunk list was normalized (CSVL-max < 10 mm)
in 15 (52%) patients after PELD, and the median time for normalization was 3 – 6 months.
Prognostic factors for the recovery of trunk list were not identified.
Limitations: Selection bias should be considered in interpreting these results.
Conclusion: Trunk list, scoliosis or lateral shift, was observed in 18% of the patients at the
time of surgery. Female gender and L4-5 disc herniation were risk factors for trunk list. Trunk
list was reversible in more than 50% of patients within 6 months of PELD.
Key words: Lumbar, scoliosis, lumbar/sciatic, trunk list, endoscope, disc, discectomy, sciatica,
spine, percutaneous endoscopic discectomy
New Levels of Vertebral Compression Fractures
after Percutaneous Kyphoplasty: Retrospective
Analysis of Styles and Risk Factors
Authors: Wan Shuanglin
Published: February 2021

Background: The causes of subsequent vertebral fractures after kyphoplasty are debated. It is
reported that most new vertebral fractures after kyphoplasty develop in adjacent vertebrae.
Objectives: We explored whether kyphoplasty increases the incidence of adjacent vertebral
fractures and identified risk factors for new vertebral compression fractures (VCFs) after kyphoplasty.
Study Design: Retrospective study.
Setting: Inpatient population of a single center.
Methods: We studied 356 patients treated with kyphoplasty from January 2008 to March 2012.
Among those patients, there were 35 new VCFs after kyphoplasty. Subsequently, these patients
were divided into 2 groups: an “adjacent fracture” group and a “nonadjacent fracture” group. In
addition, all patients treated with kyphoplasty were further assigned to either a “new fracture”
group or a “no fracture” group.
Results: The occurrence of new VCFs in the “nonadjacent fracture” group was significantly
higher than that in the “adjacent fracture” group. The average bone mineral density (BMD) of the
spine was -3.95 in the “new fracture” group and -2.86 in the “no fracture” group. The risk of
new vertebral fracture increased as the bone mineral density decreased (P < 0.05). The morbidity of
women was significantly higher in the “new fracture” group (94.29%) than in the “no fracture”
group (77.88%) (P = 0.025).
Limitations: Retrospective study at a single center.
Conclusion: New VCFs after kyphoplasty occurred most often in nonadjacent vertebrae. VCFs
after kyphoplasty were common in patients with low bone mineral density and in women,
suggesting that osteoporosis is an underlying mechanism.
Institutional Review: This study was approved by the institutional review board.
Key words: Percutaneous kyphoplasty, vertebral compression fractures, bone mineral density,
polymethylmethacrylate, adjacent vertebral fracture
Rat Model of Trigeminal Neuralgia Using
Cobra Venom Mimics the Electron Microscopy,
Behavioral, and Anticonvulsant Drug Responses
Seen in Patients
Authors: An Jian Xiong
Published: February 2021

Background: A new animal model of trigeminal neuralgia produced by injecting cobra venom
into the infraorbital nerve (ION) trunk in rats had been developed. We tested and extended the
model by observing the ultrastructural alterations of neurons and ameliorative effect of pregabalin
in cobra venom-induced pain behaviors of rats.
Objectives: The goal of this study was to prove the feasibility of the cobra venom-induced
model of trigeminal neuralgia and to demonstrate the demyelination change of ION and medulla
oblongata is the major pathological change of trigeminal neuralgia.
Study Design: An experimental study.
Setting: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation
General Hospital of China Medical University.
Methods: Experiments were carried out on male Sprague–Dawley rats. Video recordings were
taken after the cobra venom injection and pregabalin administration. Ultrastructural alterations
of ION and medulla oblongata were observed at the electron microscopic level. We also observed
alteration in pain behaviors by analysis of video recordings.
Results: Compared to the preoperative and sham-operated group rats, experimental group rats
exhibited significant changes in exploratory, resting, face-grooming, and head-shake behaviors on
3, 7, 14 days after operation (P < 0.01). The demyelination changes of ION and medulla oblongata
were evident after administration of cobra venom to the ION. Compared to the pre-treated
(no pregabalin administration) and control group rats, pregabalin group rats showed profound
changes in exploratory, resting, face-grooming, and head-shake behaviors throughout the 14 day
study period after treatment with drugs (P < 0.01).
Limitations: Ultrastructural alterations of ION and medulla oblongata were not examined after
the treatment with pregabalin.
Conclusions: Video recordings of free behaviors and pregabalin application prove the feasibility
of the rat model of trigeminal neuralgia. The results of electron micrographs are consistent
with a previous study in humans showing that the demyelination change of axons is the major
pathological change of trigeminal neuralgia. The central demyelination alterations may explain why
the mechanical threshold was found to be decreased on the non-operated side of experimental
animals.
Key words: Rat model, cobra venom, trigeminal neuralgia, free behavior, pregabalin,
demyelination
Pelvic Neuralgias by Neuro-Vascular Entrapment:
Anatomical Findings in a Series of 97
Consecutive Patients Treated by Laparoscopic
Nerve Decompression
Authors: Possover Marc
Published: February 2021

Background: Some patients have pelvic, pudendal, or low lumbar pain radiating into the legs that
is worse while sitting but differs from pudendal neuralgia. The purpose of this study was to present a
new clinical entity of neuropathic pelvic pain by pelvic neuro-vascular entrapment.
Objectives: To report about the locations of predilection for pelvic neurovascular entrapment.
Study Design: Prospective cohort pre- and post-intervention.
Setting: University referral unit specializing in advanced gynecological surgery and neuropelveology.
Methods: Patients, Intervention: In a prospective study, 97 patients presenting with intractable pelvic
neuropathic pain (pudendal pain, gluteal pain, vulvodynia, coccygodynia, and sciatic pain) underwent
laparoscopic exploration with decompression of compressed pelvic somatic nerves. The population
included 76 (78.3%) women and 21 men. Indication for laparoscopic exploration of pelvic nerves
suspected to be involved in pain has been indicated after neuropelveological work up, pelvic neuromagnetic resonance imaging (MRI) and Doppler-sonography. Pain evolution was recorded over 2 years
after the procedure.
Measurements and Main Results: Three entities were isolated: pudendal neuralgie by
compression at the less sciatic notch, sacral radiculopathy at S2-4 by compression at the infracardinal
level of the sacral plexus, and sciatica L5-S1/2 by compression at the greater sciatic notch. Pain was
worse sitting (98%), during menstrual bleeding in women, and during Valsalva maneuver, but the
pain did not wake the patients up at night and was not accompanied by neurologic dysfunctions. A
decrease in VAS scores (> 50%) at 2 years follow-up was observed in 86 patients (88.6%).
Conclusions: Neuro-vascular entrapment is a pathophysiologic phenomenon implicated in several
pelvic neuropathies. The most common are L5-S1 sciatica, pudendal neuralgia, and sacral radiculopathy.
After intraoperative confirmation, laparoscopic exploration of the entire sacral plexus is essential to
diagnose conflict. Laparoscopic decompression is a treatment of choice, based on the separation
of the offending vessel from the nerves. Those procedures are safe, with a high success rate; the
neuropelveological approach is essential in order to obtain good treatment results. The laparoscopic
approach gives the possibility of reducing morbidity and improving results by providing wider insight
into the operating field with smaller intraoperative injury.
Key words: Vulvodynia, coccygodynia, chronic pelvic pain, pudendal pain, neuro-vascular conflict
Survival Strategies for Tsunami of ICD-10-CM
for Interventionalists: Pursue or Perish!
Authors: Manchikanti Laxmaiah
Published: February 2021

The unfunded mandate for the implementation of International Classification of Diseases, 10th
Revision, Clinical Modification (ICD-10-CM) is scheduled October 1, 2015. The development of
ICD-10-CM has been a complicated process. We have endeavored to keep Interventional Pain
Management doctors apprised via a variety of related topical manuscripts. The major issues
relate to the lack of formal physician participation in its preparation. While the American Health
Information Management Association (AHIMA) and American Hospital Association (AHA) as
active partners in its preparation. Centers for Medicare and Medicaid Services (CMS) and
Centers for Disease Control and Prevention (CDC) are major players; 3M and Blue Cross Blue
Shield Association are also involved.
The cost of ICD-10-CM implementation is high, similar to the implementation of electronic
health records (EHRs), likely consuming substantial resources. While ICD-10, utilized worldwide,
includes 14,400 different codes, ICD-10-CM, specific for the United States, has expanded to
144,000 codes, which also includes procedural coding system.
It is imperative for physicians to prepare for the mandatory implementation. Conversion from
ICD-9-CM to ICD-10-CM coding in interventional pain management is not a conversion of
one to one that can be easily obtained from software packages. It is a both a difficult and
time-consuming task with each physician, early on, expected to spend on estimation at least
10 minutes per visit on extra coding for established and new patients. For interventional pain
physicians, there have been a multitude of changes, including creation of new codes and
confusing conversion of existing codes.
This manuscript describes a variety of codes that are relevant to interventional pain physicians
and often utilized in daily practices. It is our objective that this manuscript will provide coding
assistance to interventional pain physicians.
Key words: ICD-9-CM (International Classification of Diseases, Ninth revision, Clinical
Modification), ICD-10, ICD-10-CM (International Classification of Diseases, 10th Revision),
Health Insurance Portability and Accountability Act (HIPAA), Health Information Technology (HIT)
Effect of the Location of Endplate Cement
Extravasation on Adjacent Level Fracture in
Osteoporotic Patients Undergoing Vertebroplasty
and Kyphoplasty
Authors: Jesse Mary Kristen
Published: February 2021

Background: The most widely researched risk/complication following vertebroplasty (VP) or
kyphoplasty (KP) is that of adjacent level fracture (ALF). Current literature results regarding the
effect of intradiscal extravasation of cement on the risk of ALF is conflicting with about half
of the studies concluding there is no added risk with endplate extravasation and half of the
studies reporting opposite conclusions.
Objective: The purpose of the study is to further stratify the data to determine whether
specifically the location and extent of endplate cement extravasation more strongly affect ALF
risk in osteoporotic patients following either VP or balloon KP.
Study Design: Retrospective cohort study.
Setting: University teaching hospital
Methods: One hundred and fifty-six cemented levels in 80 patients, treated at a single
center between 2008 and 2012 were reviewed. Age, gender, T-score, body mass index, and
osteoporosis type (primary or secondary) were recorded. An ALF was defined as a fracture:
1) in a non-cemented vertebra; 2) adjacent to a cemented level; and 3) not due to trauma or
malignancy. Location of the cement extravasation (anterior, middle, or posterior third of the
vertebral body) and extravasation extent (percentage of the intervertebral disc height occupied
by the bolus) were measured. A logistic modeling strategy permitted examining the association
between the location and extent of extravasation and the odds of ALF.
Results: ALF occurred in 14 of the 52 patients (27%) and 20 of the 98 levels (20.4%)
remaining after exclusions. Odds of ALF were 5.9 times higher (95% CI: 1.6 to 21.2, P = 0.008)
with extravasation when compared to no leakage. Odds of ALF in a given patient were 22.6
times higher (95% CI: 3.0 to 170.9, P = 0.003) with anterior extravasation when compared
to no leakage. Leakage in the middle or posterior thirds and extent of extravasation were not
associated with ALF.
Limitations: Limitations of the study include the retrospective study design and small sample
size as well as the retrospective implementation of follow-up criteria posing risk of selection
bias.
Conclusions: Cement endplate extravasation isolated to the anterior third of the vertebral
body is associated with is significantly higher odds of ALF after VP or KP in patients with
osteoporosis.
Key words: Adjacent vertebral fracture, intradiscal leak, osteoporotic compression