bluuebunny/crossref_metadata_2025 huggingface dataset:
Occipital Nerve Stimulation with the Bion®
Microstimulator for the Treatment of Medically
Refractory Chronic Cluster Headache
Authors: Trentman Terrence L.
Published: March 2021

Background: Chronic cluster headache is a severely disabling neurological disorder.
Evidence from open-label case series suggest that occipital nerve stimulation may be
effective for the treatment of chronic cluster headache.
Objective: To evaluate the effectiveness of a microstimulator for chronic cluster
headache.
Study Design: Prospective, observational feasibility study plus medical record review.
Settings: Academic medical center.
Methods: Four patients with medically refractory chronic cluster headache underwent
implantation of a unilateral bion microstimulator. In-person follow-up was conducted
for 12 months after implantation, and a prospective follow-up chart review was carried
out to assess long term outcome.
Results: Three of the participants returned their headache diaries for evaluation. The
mean duration of chronic cluster headache was 14.3 years (range 3 to 29 years). Pain
was predominantly or exclusively retroocular/periocular. One participant demonstrated
a positive response (> 50% reduction in cluster headache frequency) at 3 months postimplant, while there were 2 responders at 6 months. At least one of the participants
continued to show > 60% reduction in headache frequency at 12 months. A chart
review showed that at 58-67 months post-implant, all 3 participants reported continued
use and benefit from stimulation. No side-shift in attacks was noted in any participant.
Adverse events were limited to 2 participants with neck pain and/or cramping with
stimulation at high amplitudes; one required revision for a faulty battery.
Limitations: Small patient population without control group. Not blinded or
randomized.
Conclusion: Unilateral occipital nerve stimulation, using a minimally invasive
microstimulator, may be effective for the treatment of medically refractory chronic
cluster headache. This benefit may occur immediately after implantation, remain
sustained up to 5 years after implantation, and occur despite the anterior location
of the pain. Prospective, randomized controlled trials of occipital nerve stimulation in
chronic cluster headache should proceed.
Key words: chronic headache, bion, peripheral nerve stimulation, cluster headache,
migraine, occipital
Preoperative Fasting Before Interventional
Techniques: Is It Necessary or Evidence-Based?
Authors: Manchikanti Laxmaiah
Published: March 2021

Background: Interventional pain management is an evolving specialty. Multiple issues
including preoperative fasting, sedation, and infection control have not been well investigated
and addressed. Based on the necessity for sedation and also the adverse events related to
interventional techniques, preoperative fasting is considered practical to avoid postoperative
nausea and vomiting. However, there are no guidelines for interventional techniques for sedation
or fasting. Most interventional techniques are performed under intravenous or conscious
sedation.
Objective: To assess the need for preoperative fasting and risks without fasting in patients
undergoing interventional techniques.
Study Design: A prospective, non-randomized study of patients undergoing interventional
techniques from May 2008 to December 2009.
Study Setting: An interventional pain management practice, a specialty referral center, a
private practice setting in the United States.
Methods: All patients presenting for interventional techniques from May 2008 to December
2009 are included with documentation of various complications related to interventional
techniques including nausea and vomiting.
Results: From May 2008 to December 2009 a total of 3,179 patients underwent 12,000
encounters with 18,472 procedures, with patients receiving sedation during 11,856 encounters.
Only 189, or 1.6% of the patients complained of nausea and 3 of them, or 0.02%, experienced
vomiting. There were no aspirations. Of the 189 patients with nausea, 80 of them improved
significantly prior to discharge without further complaints. Overall, 109 patients, or 0.9% were
minimally nauseated prior to discharge. The postoperative complaints of continued nausea were
reported in only 26 patients for 6 to 72 hours. There were only 2 events of respiratory depression,
which were managed with brief oxygenation with mask without any adverse consequence of
nausea, vomiting, aspiration, or other adverse effects.
Limitations: Limitations include the nonrandomized observational nature of the study.
Conclusion: This study illustrates that postoperative nausea, vomiting, and respiratory
depression are extremely rare and aspiration is almost nonexistent, despite almost all of
the patients receiving sedation and without preoperative fasting prior to provision of the
interventional techniques.
Key words: Interventional pain management, interventional techniques, complications,
relative risk, evidence-based medicine, preoperative fasting, nausea, vomiting, aspiration
Effect of Addition of Epidural Ketamine to
Steroid in Lumbar Radiculitis: One-Year
Follow-Up
Authors: Amr Yasser Mohamed
Published: March 2021

Background: Treating sciatica with epidural steroid injection has been a common
practice worldwide. N-methyl-D-aspartate (NMDA) receptors are an important component
of pain pathways.
Objectives: The aim of this study was to evaluate the safety and efficacy of epidurally
administered NMDA receptor antagonists (ketamine) for the treatment of chronic low
back pain secondary to radiculopathy and its effect on patients’ quality of life.
Study Design: Randomized, double blind controlled trial.
Setting: Hospital outpatient setting.
Methods: Two hundred participants aged 25 to 50 years old with a diagnosis of lumbar
radiculopathic pain secondary to disc herniation were randomized into 2 equal groups.
Group I received 80 mg of triamcinolone (2 mL) and 0.25% bupivacaine (3 mL) plus
30 mg (3 mL) of preservative free ketamine. Group II received 80 mg of triamcinolone
(2 mL) and 0.25% bupivacaine (3 mL) plus 3 mL of 0.9% saline. Pain scores were
obtained before injection, immediately after injection, one week, one month, 3 months,
6 months , 9 months and one year post injection. The Oswestry Low Back Pain Disability
Questionnaire was used at baseline and at one month, 3, 6, 9, and 12 months after
injection for assessment of quality of life. Patients were asked to report any side effects,
particularly those related to ketamine, including nausea, vomiting, visual or auditory
hallucinations, and delirium.
Results: Immediately after injection there was no statistically significant difference
between Group I and II regarding pain scale scores. After one week of injection, pain
relief was significantly better in Group I compared to Group II and then at all evaluation
times. The Oswestry Low Back Pain Disability Questionnaire score decreased significantly
(P < 0.05) from 72 (range 62- 83) and 70 (range 57- 82) to 8 (range 2 – 12) and 17 (range
9 – 27) at one month; 6 (range 4 – 12) and 18 (range 14 – 22) at 3 months; 12 (range
9 – 16) and 28 (range 22 – 34) at 6 months; 17 (range 9 – 24) and 31 (range 21 – 35)
at 9 months; and 17 (range 8 – 22) and 33 (range 20 – 37) at 12 months in the groups,
respectively. Six patients in the ketamine group showed short-lasting delusions lasting for
45 ± 12 minutes after injection.
Limitations: The limitations include a lack of placebo control.
Conclusion: Epidurally administrated ketamine seems to be a safe and useful adjunct
to epidural corticosteroid therapy in chronic lumbar radicular pain.
Key words: Ketamine, epidural, radiculopathic, pain, steroid
An Introduction to Trialing Intrathecal Baclofen
in Patients with Hemiparetic Spasticity:
A Description of 3 Cases
Authors: Harned Michael E.
Published: March 2021

Background: Intrathecal baclofen has been an effective therapy in the management of
spasticity. As interventional pain physicians are rapidly becoming the experts in intrathecal
drug delivery, they are now frequently asked to trial and implant intrathecal baclofen therapy.
While some physicians might be very comfortable with the process of trialing and implanting,
others will have next to no experience until the first consult appears on their desks. While
uncomplicated lower extremity spasticity can usually be trialed with a single-shot bolus injection,
more complicated cases of upper and lower extremities or hemiparetic spasticity need a more
delicate approach. This is the first case series in the literature reporting a trial using an indwelling
temporary catheter and inpatient admission. Moreover, while the technical aspects of intrathecal
therapy trialing and implantation might be familiar for the interventional physician, we review
the indications and goals of therapy, about which the physician may be less familiar.
Objective: To present a technique for trialing intrathecal baclofen in patients with severe
upper and lower extremities spasticity complication for which a single shot technique may be
inadequate.
Design: Case report of three patients.
Setting: Tertiary-care referral medical center.
Patients: A 30-year-old man with severe spasticity of the right upper and lower extremities
with preserved left-sided function due to diffuse axonal injury. A 45-year-old woman with
traumatic brain injury and severe spasticity of the left upper extremity with minimal dysfunction
in the right upper extremity. A 34-year-old woman with Multiple Sclerosis and severe spasticity
in the right upper extremity and bilateral lower extremities.
Intervention: Placement of a temporary intrathecal catheter and an inpatient trial of
intrathecal baclofen.
Results: In all patients, there was significant improvement in spasticity as documented by
decreased Modified Ashworth Scale scores while preserving motor strength and coordination in
the unaffected extremities.
Limitations: Retrospective review of 3 cases in a single center.
Conclusions: Trialing for baclofen is usually performed as a single shot bolus. For patients
with severe hemiparetic spasticity or in patients where weakness in the unaffected limb might
significantly affect quality of life, this trialing technique may be inadequate. In these patients,
placement of a temporary intrathecal catheter and inpatient admission may be a more effective
trial method.
Key words: Baclofen, intrathecal drug delivery, spasticity, multiple sclerosis, traumatic brain
injury
Interlaminar Versus Transforaminal Epidural
Steroids for the Treatment of Subacute Lumbar
Radicular Pain: A Randomized, Blinded,
Prospective Outcome Study
Authors: Gharibo Christopher G.
Published: March 2021

Background: There is uncertainty in the literature over the relative effectiveness of lumbar
epidural interlaminar (IL) steroid injection versus transforaminal (TF) steroid injection for
lumbar radiculopathy. Most studies to date have been retrospective, or technically focused.
Objective: To complete a randomized, blinded, prospective outcome study of the
short-term benefit for IL versus TF epidural steroids for the treatment of subacute lumbar
radicular pain.
Study design: Prospective, randomized, blinded, subacute efficacy trial.
Setting: Tertiary care pain management center, major metropolitan city, United States
Methods: After institutional review board approval, 42 age-matched patients with
similar lower back pain and unilateral radicular symptoms were enrolled and randomized
in a patient and evaluating physician blinded trial to IL or TF epidural steroids from 2007
through 2009. Prior to intervention and 10-16 days after injection, each participant was
evaluated by questionnaire and physical exam by an independent physician. All injections
were performed by the same physician. Thirty-eight participants completed the study, 18
in the IL group and 20 in the TF group. Four participants required a repeat injection, and 2
participants crossed over to the alternative injection type (IL to TF).
Results: Overall, physical exam, diagnostic testing, disability, activity, depression measures,
and opioid pill use were similar between the 2 groups, both pre-injection baseline and postinjection improvement. In primary outcomes, the post-injection follow-up Numeric Rating
Scale (NRS) was more greatly reduced in the TF group. The NRS decreased from 7.0 ± 1.9 to
3.9 ± 3.1 (mean values +/- standard deviation) in the IL group and 6.4 ± 2.1 to 1.7 ± 1.4 in
the TF group. The Oswestry Disability Index was reduced from 37.5 ± 12.6 to 19.0 ± 16.7
in the IL group and 38.3 ± 6.4 to 21.6 ± 16.8 in the TF group. In secondary outcomes, the
depression scale was reduced from 4.39 ± 3.22 to 2.28 ± 3.20 in the IL group and 4.10 ±
1.94 to 1.65 ± 1.63 in the TF group. Walking tolerance was increased from 8.1 ± 4.6 blocks
to 10.6 ± 4.4 in the IL group and 8.9 ± 5.3 blocks to 11.8 ± 4.2 in the TF group.
Limitations: The study did not examine long-term outcomes. A single experienced
interventionalist performed all injections.
Conclusion: Results suggest that patients may experience greater subjective relief, at
least initially, from TF epidural steroid injections over IL. However, more objective, and likely
subacute, therapeutic effects are similar.
Key words: epidural, steroids, interlaminar, transforaminal, lumbar, lumbosacral,
radicular, low back pain
Spinal Cord Stimulation for the Treatment of
Chronic Renal Pain Secondary to Uretero-Pelvic
Junction Obstruction
Authors: Kim Chong H.
Published: March 2021

Background: Chronic renal pain secondary to uretero-pelvic junction obstruction (UPJO) is common
but remains poorly understood. Patients with UPJO experience frequent infections, renal calculi
and pain. Management options for patients with this condition are traditionally limited to surgical
interventions to eliminate the obstruction.
Spinal Cord Stimulation (SCS) has gained widespread popularity for the treatment of numerous
conditions from complex regional pain syndrome to failed back syndrome. With continued success,
the possible use of SCS has steadily increased.
Although a significant number of patients with severe chronic renal pain will transiently respond to
analgesics and physical interventions such as autonomic sympathetic blocks, substantial long-term
pain relief is usually lacking. SCS therefore might be a welcome addition to the treatment of moderate
to severe chronic renal pain. .
Objective: This article presents a case of using spinal cord stimulation in the management of chronic
renal pain secondary to Uretero-pelvic junction obstruction.
Design: Case report
Setting: Academic University Pain Management Center
Methods: A 38-year old female presented with a 15-year history of persistent right sided flank pain
secondary to congenital uretero-pelvic junction obstruction. After failing to respond adequately to
stenting, medications and nerve blocks, a trial of spinal cord stimulation and subsequent permanent
implantation of a spinal cord stimulator (SCS) were performed.
Results: The patient reported significant improvement in pain, overall functioning and no
consumption of opioids during the SCS trial and following system implant.
Limitations: A case report.
Conclusion: Spinal cord stimulation might be an option in the management of chronic renal pain
secondary to Uretero-pelvic junction obstruction.
Key words: spinal cord stimulation, renal pain, uretero-pelvic jnction obstruction, visceral pain, flank
pain, pelvic pain
Predictors for Persistent Neuropathic Pain
– A Delphi Survey
Authors: Boogaard Sabine
Published: March 2021

Background: Chronic neuropathic pain has a major effect on quality of life. In order to
prevent neuropathic pain from becoming chronic and improve neuropathic pain care, it is
important to identify predictors associated with the persistence of neuropathic pain.
Objective: To identify potential predictors associated with the persistence of neuropathic
pain.
Study Design: A 2-round Delphi study.
Setting: University Medical Center and Pain Management Research Center
Methods: A 2-round Delphi study was conducted among 17 experts in the field of
neuropathic pain. Selection of the panel was based on the citation index ranking for
neuropathic pain-related research and/or membership in the neuropathic pain special
interest group of the International Association for the Study of Pain (IASP), complemented
with experts with demonstrated field knowledge.
Potential predictors were categorized according to the International Classification of
Functioning, Disability and Health model. Participants were asked to identify important
predictors, suggest new predictors, and grade the importance on a 0-10 scale. For the
second round, predictors were considered important if the median score was ≥ 7 and the
interquartile range (IQR) ≤ 3.
Results: In the first round, 20 predictors were selected and 58 were added by the
experts (patient characteristics [15], environmental factors [25], functions & structure [4],
participation & health related quality of life [14]). In the second round, 12 predictors were
considered important (patient characteristics [4; e.g., depression, pain catastrophizing],
environmental factors [surgery as treatment for neuropathic pain], functions & structure
[6; e.g., allodynia, duration of the complaints], participation & trait anxiety/depression as a
part of health related quality of life). Presence of depression and pain catastrophizing were
considered the most important predictors for chronic neuropathic pain (median ≥ 8;IQR ≤ 2).
Limitations: The study design did not include plenary discussion among the experts. The
meaning of the individual topics used in this study could have been subject to interpretation bias.
Conclusions: Overall, psychological factors and factors related to sensory disturbances
were considered important predictors for persistence of neuropathic pain. Activity related
factors and previously received paramedical and alternative treatment were considered to be
less important. The list of possible predictors obtained by this study may serve as a basis for
development of a clinical prediction rule for chronic neuropathic pain.
Key words: Neuropathic pain, chronic pain, persistence, Delphi study, opinion, predictors,
ICF model.
Painful Rheumatoid Arthritis
Authors: Seidner Pya
Published: March 2021

Rheumatoid arthritis is a crippling disease that is often associated with severe pain,
suffering, and diminished function, thereby detracting from an optimal quality of life.
Over the past decade a greater appreciation of the pathophysiology of rheumatoid
arthritis has been gained. In the past “decade of pain research,” biologic agents which
may modify rheumatoid arthritis have emerged as potent therapeutic antirheumatic drugs.
Biologic agents include 5 tumor necrosis factor alpha inhibitors (etanercept, infliximab,
adalimumab, golimumab, certolizumab pegol), interleukin-1 blockers (anakinra),
monocloncal antibodies against B cells (rituximab), T cell costimulation blocker (abatacept),
and interleukin-6 inhibitors (tocilizumab).
Currently, utilizing therapy aimed at targeting various abnormalities of rheumatoid arthritis
may be possible. It appears that the combined use of etanercept and methotrexate may
improve the imbalance of Th1/Th2 and Th17/regulatory T cells (Treg) (and related cytokines)
often seen in rheumatoid arthritis. Furthermore, this improvement in Tcell ratios/cytokines
is also associated with improvement in clinical indicators of rheumatoid arthritis severity.
Although rheumatologists are generally the specialists “called on” to manage complex
patients with rheumatoid arthritis, pain specialists may be asked to join interdisciplinary
teams managing patients with advanced refractory rheumatoid arthritis with severe pain
since one of the most common and debilitating symptoms of rheumatoid arthritis is pain.
Thus, pain specialists should have some appreciation of the current thoughts regarding
rheumatoid arthritis pathophysiology and treatment.
This narrative review of rheumatoid arthritis is intended to familiarize the interventional
pain specialist with current concepts surrounding rheumatoid arthritis.
Key words: Rheumatoid Arthritis, Pain, DMARDs, biological agengs, TNF inhibitors
A Systematic Review of Observational Studies
on the Effectiveness of Opioid Therapy for
Cancer Pain
Authors: Colson James
Published: March 2021

Background: The prevalence of cancer-related pain and residual pain in cancer
survivors is high. Opioids serve as the gold standard for treating moderate to severe
cancer pain. The evaluation of the effectiveness of opioids in chronic non-cancer pain
has shown a lack of effectiveness, or rather weak evidence for some of the drugs. In
contrast, in cancer pain, opioids are expected to be very effective. Due to the nature
of the disease, there is evidence of a paucity of randomized trials investigating opioid
effectiveness in cancer pain on a long-term basis. Consequently, the effectiveness
of opioids in managing cancer-related pain warrants further evidence-based review
beyond randomized trials, including observational studies and case reports.
Methods: The comprehensive literature search was conducted for the period 1996
through June 2010. Databases for the search included PubMed, EMBASE, Cochrane
Reviews, and clinicaltrails.gov, along with reviews and cross references.
Methodologic quality assessment of the observational studies managing chronic
cancer pain with opioids was conducted utilizing the Agency for Healthcare
Research and Quality (AHRQ) criteria for observational studies. Analysis of evidence
included 5 levels of evidence developed by the United States Preventive Services Task
Force (USPSTF) ranging from Level I to III with 3 subcategories in Level II. Grading
recommendations were based on Guyatt et al’s recommendations with 6 levels: 3 in
the strong category and 3 in the weak category.
Results: This evaluation is of 18 manuscripts considered for inclusion; 7 manuscripts
met the inclusion criteria based on AHRQ quality assessment. Level of evidence for
opioid therapy in cancer pain was Level II-3, and recommendations were 1C/strong
recommendation based on observational studies, which could change based on
future evidence.
Conclusion: This systematic review of observational studies indicates Level II3 evidence for effectiveness of opioids in cancer pain therapy, with 1C/strong
recommendation based on observational studies, which could change based on
future evidence.
Key words: Chronic pain, cancer pain, non-cancer pain, randomized trials,
observational studies, case reports, opioids, effectiveness
Effect of Fluoroscopically Guided Caudal
Epidural Steroid or Local Anesthetic Injections
in the Treatment of Lumbar Disc Herniation and
Radiculitis: A Randomized, Controlled, Double
Blind Trial with a Two-Year Follow-Up
Authors: Manchikanti Laxmaiah
Published: March 2021

Background: Lumbar disc herniation and radiculitis are common elements of low back and
lower extremity pain. Among minimally invasive treatments, epidural injections are one of the most
commonly performed interventions. However, the literature is mixed about their effectiveness in
managing low back and lower extremity pain. In general, individual studies and systematic reviews of
epidural steroid injections have been hampered by their study design, baseline differences between
treatment groups, inadequate sample sizes, highly controlled settings, lack of validated outcome
measures, and the inability to confirm the injectate location because fluoroscopy was not used.
Study Design: A randomized, controlled, double blind, active control trial.
Setting: A private, interventional pain management practice, specialty referral center in the
United States.
Objectives: To assess the effectiveness of fluoroscopically directed caudal epidural injections with
local anesthetic with or without steroids in managing chronic low back and lower extremity pain
in patients with disc herniation and radiculitis.
Methods: One hundred twenty patients were randomized to two groups: Group I received 10
mL caudal epidural injections of local anesthetic, lidocaine 0.5%; Group II patients received caudal
epidural injections of 0.5% lidocaine, 9 mL, mixed with 1 mL of steroid.
Outcome Assessment: Multiple outcome measures were utilized. The primary outcome
measures were Numeric Rating Scale (NRS) and the Oswestry Disability Index 2.0 (ODI). Secondary
outcome measures were employment status and opioid intake.
Significant pain relief improvement was defined as 50% or more improvement in NRS and ODI scores.
Results: In the successful category, 77% of Group I had significant pain relief of ≥ 50% and functional
status improvement of ≥ 50% reduction in ODI scores; in Group II it was 76%, whereas overall it was
60% and 65% in Groups I and II. Over the two years, Group I had an average number of procedures
of 5.5 ± 2.8; Group II was 5.3 ± 2.4. Even though there was no significant difference in overall relief
between the two groups, the average relief for each procedure was superior for steroids.
Limitations: Presumed limitations of this evaluation include lack of a placebo group.
Conclusion: Caudal epidural injections of local anesthetic with or without steroids might be an
effective therapy for patients with disc herniation or radiculitis. The present evidence illustrates the
potential superiority of steroids compared with local anesthetic at two year follow up based on
average relief per procedure.
Key words: Chronic low back pain, caudal epidural injections, disc herniation, radiculitis, lower
extremity pain, local anesthetic, steroids
Removal of a Vertebral Metastatic Tumor
Compressing the Spinal Nerve Roots via
a Single-Port, Transforaminal, Endoscopic
Approach Under Monitored Anesthesia Care
Authors: Kim Kyung-Hoon
Published: March 2021

Spinal cord or nerve root compression from an epidural metastasis occurs in 5-10% of patients with
cancer and in up to 40% of patients with preexisting nonspinal bone metastases. Most metastatic
spine diseases arise from the vertebral column, with the posterior half of the vertebral body being
the most common initial focus, and/or the paravertebral region, tracking along the spinal nerves to
enter the spinal column via the intervertebral foramina.
An 82-year-old man diagnosed with sigmoid colon cancer and liver metastases experienced
intractable pain described as being like an electric shock on the right T11 dermatome. Imaging
studies revealed a huge metastatic mass destroying the right posterior T11 body and pedicle and
compressing the right posterior spinal cord and nerve roots.
Even after using neuropathic medication and a neural blockade, the extreme paroxysmal pain
continued. Considering his elderly, debilitated state and life expectancy, removal of the vertebral
metastatic tumor compressing the spinal nerve roots via a single-port, transforaminal, endoscopic
approach and percutaneous vertebroplasty (PVP) under monitored anesthetic care (MAC), rather
than 3-port endoscopic surgery and corpectomy with or without fusion under general anesthesia
with lung deflation, was decided upon and scheduled prior to radiotherapy.
A needle was placed into the intervertebral foramen under fluoroscopy in the same manner as a
transforaminal epidural block at T11. A guidewire was inserted into the needle after the needle
stylet had been removed. An obturator dilator was inserted over theguidewire, and a working
sleeve was inserted over the dilator. After the dilator was removed, a spinal endoscope with a 2.7
mm working channel was placed over the guidewire. Careful removal of the tumor emboli during
verbal interaction with the patient was performed under MAC using dexmedetomidine, fentanyl,
and ketorolac. PVP at T11 was performed through the right osteolytic pedicle. The paroxysmal pain
disappeared immediately after the operation without any complications.
Removal of a vertebral metastatic tumor compressing the spinal nerve roots via a single-port,
transforaminal, endoscopic approach under monitored anesthesia care without lung deflation may be
an effective and safe modality for minimally invasive pain management of a single-level spinal tumor
metastasis causing intractable radicular pain in patients with cancer who have generalized debilitation.
Key words: Combined anesthetics, endoscope, intractable pain, minimally invasive, neoplasm
metastasis, palliative care, radiotherapy, spinal nerve roots, surgical procedures, vertebroplasty
Efficacy of Intrathecally Administered
Dexmedetomidine Versus Dexmedetomidine
With Fentanyl in Patients Undergoing Major
Abdominal Cancer Surgery
Authors: Mohamed Sahar A.
Published: March 2021

Background: Most of the clinical experience gained in the use of intrathecal α2- adrenoceptor
agonists has been described with clonidine. Human studies using a combination of intrathecal
dexmedetomidine and local anesthetics are lacking.
Objectives: A safety investigation and comparison of the analgesic efficacy of intrathecally
administered dexmedetomidine or dexmedetomidine combined with fentanyl 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 intrathecally either 10 mg
bupivacaine 0.5% (control group, n = 30), or 10 mg bupivacaine 0.5% plus 5 µg dexmedetomidine
(dexmedetomidine group, n = 30), or 10 mg bupivacaine 0.5% plus 5 µg dexmedetomidine and
25µg fentanyl (dexmedetomidine+ group, n = 30). Assessment parameters included hemodynamics,
sedation score, pain severity, time of first analgesics request, total analgesic consumption, and side
effects in the first 24 hours.
Results: The mean intraoperative heart rate was significantly reduced in the dexmedetomidine
group (P < 0.05) and the dexmedetomidine+ group (P < 0.05) compared with the control group.
Also, there was a significant reduction in mean intraoperative systolic and diastolic blood pressure
in the dexmedetomidine group (P < 0.05) and the dexmedetomidine+ group (P < 0.05) compared
with the control group, with no significant differences in postoperative hemodynamics or sedation
scores among all the study groups.
The mean visual analog scale scores showed a significant reduction immediately and at 12 hours
postoperatively in both the dexmedetomidine and dexmedetomidine+ groups compared to the
control group.
The mean time of the first analgesic request was significantly prolonged in the dexmedetomidine
group (3.30 ± 0.87 hours, P < 0.01) and the dexmedetomidine+ group (5.41 ± 1.23 hours, P <
0.01) compared with the control group (0.23 ± 0.11 hours). Moreover, postoperative tramadol
consumption was significantly reduced in the dexmedetomidine (142.85 ± 13.04 mg, P < 0.01)
and the dexmedetomidine+ (131.25 ± 11.96 mg, P < 0.01) groups, compared with the control
group (310.0 ± 12.08 mg). No significant serious adverse effects were recorded during the study.
Limitations: This study is limited by its sample size.
Conclusion: Dexmedetomidine 5 µg given intrathecally improves the quality and the duration of
postoperative analgesia and also provides an analgesic sparing effect in patients undergoing major
abdominal cancer surgery. Furthermore, the addition of intrathecal fentanyl 25 µg has no valuable
clinical effect.
Key words: dexmedetomidine, fentanyl, intrathecal, postoperative pain
The Efficacy of Patient Education in Whiplash
Associated Disorders: A Systematic Review
Authors: Meeus Mira
Published: March 2021

Background: Until now, there is no firm evidence for conservative therapy in patients with chronic
Whiplash Associated Disorders (WAD). While chronic WAD is a biopsychosocial problem, education
may be an essential part in the treatment and the prevention of chronic WAD. However, it is still
unclear which type of educative intervention has already been used in WAD patients and how
effective such interventions are.
Objective: This systematic literature study aimed at providing an overview of the literature regarding
the currently existing educative treatments for patients with whiplash or WAD and their evidence.
Study Design: Systematic review of the literature
Methods: A systematic literature search was conducted in the following databases: Pubmed,
Springerlink, and Web of Science using different keyword combinations. We included randomized
controlled clinical trials (RCT) that encompass the effectiveness of education for patients with WAD.
The included articles were evaluated on their methodological quality.
Results: Ten RCT’s of moderate to good quality remained after screening. Both oral and written
advice, education integrated in exercise programs and behavioral programs appear effective
interventions for reducing pain and disability and enhancing recovery and mobility in patients with
WAD. In acute WAD, a simple oral education session will suffice. In subacute or chronic patients
broader (multidisciplinary) programs including education which tend to modulate pain behavior and
activate patients seems necessary.
Limitations: Because of limited studies and the broad range of different formats and contents of
education and different outcome measures, further research is needed before solid conclusions can
be drawn regarding the use and the modalities of these educational interventions in clinical practice.
Conclusion: Based on this systematic literature study is seems appropriate for the pain physician to
provide education as part of a biopsychosocial approach of patients with whiplash. Such education
should target removing therapy barriers, enhancing therapy compliance and preventing and treating
chronicity. Still, more studies are required to provide firm evidence for the type, duration, format, and
efficacy of education in the different types of whiplash patients.
Key words: Systematic review, whiplash, whiplash associated disorders, education, patient advice,
information, chronic pain, biopsychosocial approach
A Predictive Model for Intrathecal Opioid Dose
Escalation for Chronic Non-Cancer Pain
Authors: Duarte Rui V.
Published: March 2021

Background: Tolerance is defined as a phenomenon in which exposure to a drug results in a
decrease of an effect or the requirement of a higher dose to maintain an effect. The fear of a
patient developing opioid tolerance contributes regularly to the stigmatization and withholding
of intrathecal opioid therapy for chronic pain of non-cancer origin.
Objectives: The aim of this study was to describe the intrathecal opioid dose escalation
throughout the years in chronic non-cancer pain patients. A secondary objective was the
development of an intrathecal opioid dose predictive model.
Study Design: Retrospective assessment of medical records.
Setting: Department of Pain Management, Russells Hall Hospital, Dudley, United Kingdom.
Methods: Medical records were reviewed and pump refill notes screened from the date of
implant through November 2010 for 31 patients undertaking continuous intrathecal opioid
therapy. All the patients included had undertaken a minimum of 6 years of intrathecal therapy
when the data were collected.
Results: Significant increases in the intrathecal morphine dose were verified between follow-up
at one year and all subsequent observations, F (2.075, 62.238) = 13.858, 0 < 0.001, but ceased
to be significant from year 3 onwards, indicating stability of the morphine dose, F (3, 90) = 2.516,
P = 0.63. A model that accounts for 76% of the variability of morphine doses at year 6 based on
year 2 assessment combined with duration of pain prior to initiation of intrathecal therapy was
developed: year 6 dose = -0.509 + (1.296 x [year 2 dose]) + (0.061 x [duration of pain]).
Limitations: Retrospective study.
Conclusion: The opioid dose escalation observed throughout the years was modest and not
significant following year 3 of therapy. The model developed has the potential to assist the
physician in the identification of a need for alternative treatment strategies. Furthermore, since
many of the pump replacements are performed prior to year 6, it can also assist in the informed
decision of the benefits and risks of the maintenance of this therapy.
Key words: Chronic pain, non-cancer pain, intrathecal opioid therapy, opioid dose escalation,
predictive mode
Central Adaptation of Pain Perception in
Response to Rehabilitation of Musculoskeletal
Pain: Randomized Controlled Trial
Authors: Lars L. Andersen
Published: March 2021

Background: Understanding the mechanisms of long-standing musculoskeletal pain
and adaptations in response to physical rehabilitation is important for developing optimal
treatment strategies. The influence of central adaptations of pain perception in response
to rehabilitation of musculoskeletal pain remains unclear.
Objectives: To investigate the effect of neck/shoulder resistance training on pressure
pain threshold (PPT) of the painful neck/shoulder muscles (upper trapezius) and a nonpainful reference muscle of the leg (tibialis anterior) in adults with neck/shoulder pain.
Study Design: Examiner-blinded, parallel-group randomized controlled trial with
allocation concealment. Trial registration: ISRCTN60264809
Setting: Office workplaces in the capital of Denmark
Methods: The study contained 198 adults with frequent neck/shoulder pain (174
women and 24 men, mean: age 43 years, duration of pain 186 days during the previous
year, computer use 93% of work time) were randomly allocated to 10 weeks of specific
resistance training for the neck/shoulder muscles for 2 or 12 minutes per day 5 times a
week, or weekly information on general health (control group). Primary outcomes were
changes in PPT of the painful neck/shoulder muscles (upper trapezius) and a distant nonpainful reference muscle (tibialis anterior) at 10 weeks.
Results: PPT of both the trained painful trapezius and the non-trained reference muscle
of the leg increased more in the training groups compared with the control group (P
< 0.05), providing evidence of central adaptations. The change in PPT of the reference
muscle was of similar magnitude to that of the painful muscle. Compared with the control
group, the change in PPT of the trapezius and tibialis anterior was 31 (95% CI 3 to 60)
kPa and 36 (8 to 65) kPa in the 2 min group, respectively, and 29 (1 to 58) kPa and 36 (7
to 64) kPa in the 12 min group.
Limitations: Blinding of participants is not possible in behavioural interventions.
Conclusion: Central adaptations of pain perception occur in response to rehabilitation of
musculoskeletal pain. Thus, treating pain in one region of the body reduces sensitivity to
pressure in other regions of the body. Clinicians and researchers may use this knowledge
to better understand adaptations of pain perception in patients with musculoskeletal pain.
Key words: Hyperalgesia, neck pain, trapezius myalgia, pressure pain threshold, physical
exercise
Ziconotide Adverse Events in Patients with
Cancer Pain: A Multicenter Observational Study
of a Slow Titration, Multidrug Protocol
Authors: Dupoiron Denis
Published: March 2021

Background: Ziconotide is a new analgesic agent administered intrathecally. It is challenging
to use and can induce several and sometimes serious adverse events. A low initial dosage
followed by slow titration may reduce serious adverse events.
Objective: To determine whether a low starting dosage of ziconotide, followed by slow
titration, decreases the incidence of major adverse events associated with ziconotide when
used for intractable cancer pain.
Study Design: Observational cohort study.
Setting: Three French cancer centers.
Methods: Patients with incurable cancer causing chronic pain rated above 6/10 on
a numerical scale while receiving high-dose opioid therapy (more than 200 mg/d of oral
morphine equivalent) and/or exhibiting severe opioid-related adverse events received
intrathecal infusions of ziconotide combined with morphine, ropivacaine, and clonidine.
Results: Seventy-seven patients were included. Adverse events were recorded in 57%
of them; moderate adverse events occurred in 51%. Adverse events required treatment
discontinuation in 7 (9%) including 5 (6%) for whom a causal role for ziconotide was highly
likely; among them 4 (5%) were serious. All patients experienced a significant and lasting
decrease in pain intensity (by 48%) in response to intrathecal analgesic therapy that included
ziconotide.
Limitations: Limitations include the nonrandomized, observational nature of the study.
Determining the relative contributions of each drug to adverse events was difficult, and some
of the adverse events manifested as clinical symptoms of a subjective nature.
Conclusions: The rates of minor and moderate adverse events were consistent with
previous reports. However, the rate of serious adverse events was substantially lower. Our
study confirms the efficacy of intrathecal analgesia with ziconotide for relieving refractory
cancer pain. These results indicate that multimodal intrathecal analgesia in patients with
cancer pain should include ziconotide from the outset in order to provide time for subsequent
slow titration.
Key words: Ziconotide, adverse events, intrathecal therapy, cancer pain, morphine,
ropivacaine, clonidine.
Altered Perception of Distorted Visual
Feedback Occurs Soon After Whiplash Injury:
An Experimental Study of Central Nervous
System Processing
Authors: Nijs Jo
Published: March 2021

Background: Sensory and motor system dysfunctions have been documented in a proportion of
patients with acute whiplash associated disorders (WAD). Sensorimotor incongruence may occur and
hence, may explain pain and other sensations in the acute stage after the trauma.
Objectives: The present study aimed at 1) evaluating whether a visually mediated incongruence
between sensory feedback and motor output increases symptoms and triggers additional sensations
in patients with acute WAD, 2) investigating whether the pattern of sensations in response to
sensorimotor incongruence differs among patients suffering from acute and chronic WAD, and
healthy controls.
Study Design: Experimental study.
Setting: Patients with acute WAD were recruited within one month after whiplash injury via the
emergency department of a local Red Cross medical care unit, the Antwerp University Hospital, and
through primary care practices. Patients with chronic WAD were recruited through an advertisement
on the World Wide Web and from the medical database of a local Red Cross medical care unit.
Healthy controls were recruited from among the university college staff, family members, and
acquaintances of the researchers.
Methods: Thirty patients with acute WAD, 35 patients with chronic WAD, and 31 healthy persons
were subjected to a coordination test. They performed congruent and incongruent arm movements
while viewing a whiteboard or mirror.
Results. Twenty-eight patients with acute WAD reported sensations such as pain, tightness, feeling
of peculiarity, and tiredness at some stage of the test protocol. No significant differences in frequencies
and intensities of sensations were found between the various test stages (P > .05). Significantly more
sensations were reported during the incongruent mirror stage compared to the incongruent control
stage (P < .05). The pattern in intensity of sensations across the congruent and incongruent stages
was significantly different between the WAD groups and the control group.
Limitations: The course and prognostic value of susceptibility to sensorimotor incongruence after
an acute whiplash trauma are not yet clear from these results. A prospective longitudinal study with
an expanded study population is needed to investigate if those with a lowered threshold to visually
mediated sensorimotor incongruence in the acute stage are at risk to develop persistent pain and
disability.
Conclusion: Patients with acute WAD present an exacerbation of symptoms and additional
sensations in response to visually mediated changes during action. These results indicate an altered
perception of distorted visual feedback and suggest altered central sensorimotor nervous system
processing in patients with acute WAD.
Key words: Sensorimotor incongruence, visually mediated changes, whiplash, sensations, acute
pain, chronic pain, altered central sensorimotor processing, central nervous system.
The Efficacy of Transforaminal Epidural Steroid
Injection by the Conventional Technique in FarLateral Herniation of Lumbar Disc
Authors: Park Joon-Hee
Published: March 2021

Background: Owing to the anatomical difference between the far lateral herniation of
the lumbar disc (FHLD) and the intraspinal herniation of lumbar disc (iHLD), the outcome of
transforaminal epidural steroid injections (TFESI) in patients with FHLD seems to be different
from that in patients with iHLD. However, few studies have evaluated the efficacy of TFESI in
FHLD.
Objective: To evaluate and compare the efficacy of TFESI in FHLD and iHLD patients.
Study Design: A retrospective design.
Methods: There were 15 and 70 patients in the FHLD and iHLD groups, respectively.
Patients received a fluoroscopically guided TFESI. Failure rates of TFESI were recorded, and
questionnaires, including a visual analog scale (VAS) for leg pain and Oswestry Disability Index
(ODI) were administered before the initial injection, at 2 weeks, 6 weeks, and 12 weeks after
the injections.
Results: There was no failure for TFESI in the iHLD group, while 9 patients had to undergo
alternative blocks in the FHLD group due to lancinating leg pain when the needle was advanced
for TFESI. In the iHLD group, there was a statistically significant improvement in the VAS and
ODI score 12 weeks after injection. Considering only successful cases of the FHLD group,
significant improvement in the VAS and ODI score was also demonstrated in the FHLD group
12 weeks after injection. Moreover, there was no statistically significant difference of the VAS
and ODI between the both groups.
Limitations: A relatively small numbers of cases were included in the FHLD group.
Conclusion: The current study suggests that an alternative needle placement technique for
TFESI appears to be necessary for FHLD patients.
Key words: Far lateral herniation of lumbar disc, intraspinal herniation of lumbar disc,
transforaminal epidural steroid injection, safe triangle, herniated lumbar disc, visual analog
pain scale, Oswestry disability index, radiculopathy
Salivary Cortisol Concentration Changes After
Epidural Steroid Injection
Authors: Moon Ho Sik
Published: March 2021

Background: Epidural steroid injections (ESI) are therapeutically useful for the treatment of
herniated intervertebral discs and spinal stenosis. However, there is a lack of evidence-based data
about the safety of steroids.
Objectives: The aim of this study was to determine the period of hypothalamus-pituitary-adrenal
(HPA) axis suppression by salivary cortisol measurements after a single epidural injection of 40 mg
of triamcinolone.
Study Design: Clinical observational pilot study.
Setting: Outpatient follow-up.
Methods: In this study, 8 patients with lumbar intervertebral disc herniation or spinal stenosis were
enrolled. All patients had received ESI (triamcinolone 40 mg) under C-arm guidance. Salivary cortisol
concentrations were assessed between 8:00 am and 9:00 am; both before and after ESI (Day 0
[the day prior to injection], 1, 3, 5, 7, 14, 21, 28). Additionally, body weight, blood pressure, 0–10
numeric rating scale (NRS), and fasting blood sugar levels were evaluated.
Results: HPA axis suppression was observed in all patients for 19.9 ± 6.8 days after ESI (salivary
cortisol < 0.1 μg/mL). In total, 5 of 8 patients reached baseline salivary cortisol concentrations
within the clinical trial period. The time taken to reach baseline concentrations after ESI was 19.4
± 8.3 days. The period of HPA axis suppression was not correlated with baseline salivary cortisol
concentrations, and NRS scores.
Limitations: Adrenal insufficiency cannot be confirmed by simple salivary cortisol measurements.
Furthermore, the period studied was too short for all patients’ HPA axis function to reach the
baseline value. Finally, the study design does not allow for the confounding effects of pain and
stress on cortisol levels.
Conclusions: HPA axis function was suppressed after ESI until Day 21 and returned to the normal
range after 19.9 ± 6.8 days. Therefore, we suggest that the minimal interval between ESI treatments
should be at least one month. In addition, we report that salivary cortisol measurements are very
useful diagnostic predictors of HPA function.
Key words: Epidural injections, salivary, steroids, HPA, complications, cortisol, herniated discs,
spinal stenosis.