Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats.

BACKGROUND: Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity. METHODS: Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarisation, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques. RESULTS: SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarisation and decreased macrophage infiltration and Schwann cell loss were downregulated. CONCLUSION: SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.

The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Intraoperative neurophysiological monitoring and spinal cord stimulator implantation.

INTRODUCTION: Spinal cord injury (SCI) is one of the most dreaded complications after spinal cord stimulation (SCS) implantation surgery. As a result, intraoperative neurophysiological monitoring (IONM) has been proposed to avoid accidental damage to nervous structures under anesthesia and confirm positioning for optimal stimulation. Our study uses a large administrative claims database to determine the 30-day risk of SCI after SCS implantation. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare Supplemental Databases from 2016 to 2019. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up, IONM use, the type of sedation used during the procedure, and subsequent SCI were identified using administrative codes. In addition, logistic regression was used to examine the relationship between various risk factors and subsequent SCI. RESULTS: A total of 9676 patients underwent SCS surgery (64.7% percutaneous implants) during the study period. Nine hundred and forty-four (9.75%) patients underwent SCS implantation with IONM. Conscious sedation, Monitored Anesthesia Care anesthesia, and general anesthesia were used in patients with 0.9%, 60.2%, and 28.6%, respectively. Eighty-one (0.8%) patients developed SCI within 30 days after SCS implant surgery. The SCI rate was higher in the group that underwent IONM (2% vs 0.7%, p value <0.001) during the implantation procedure, reflecting the underlying risk. After adjustment for other factors, the OR of SCI is 2.39 (95% CI: 1.33 to 4.14, p value=0.002) times higher for those with IONM than those without IONM. CONCLUSIONS: Increased SCI risk among patients with IONM likely reflects higher baseline risk, and further research is needed for risk mitigation.

Intrathecal Drug Delivery Systems for Cancer Pain Control: Insights on Current Contemporary Practices in the US.

OBJECTIVES: Among patients with cancer with moderate to severe, intractable pain, intrathecal drug delivery using an intrathecal drug delivery system (IDDS) offers effective pain control. In this study, we evaluate the trends of IDDS therapy among patients with cancer, associated comorbidities, complications, and outcomes, using a large representative US administrative inpatient data base. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) data base contains data from 48 states and the District of Columbia. The NIS was used to identify patients with cancer who underwent IDDS implantation between 2016 and 2019. Patients with cancer with intrathecal pumps for the treatment of chronic pain were identified using administrative codes. Baseline demographics, hospital characteristics, type of cancer associated with IDDS implantation, palliative care encounters, hospitalization costs, length of stay, and prevalence of bone pain were evaluated in the study. RESULTS: A total of 22,895 (0.32%) individuals with hospital admission for IDDS surgery were included for analysis among 7.06 million individuals with cancer in the final cohort. The IDDS cohort consisted of patients predominantly in the 65-to-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). The top five cancers in patients receiving IDDS were lung (27.15%), colorectal (24.9%), liver (16.44%), bone (8.01%), and liver (7.99%) cancer. In addition, the length of stay was six days (interquartile range [IQR] four-nine days) and the median cost of hospital admission was $29,062 (IQR $19,413-$42,261) in the patients who received an IDDS. These factors were greater than those in patients without IDDS. CONCLUSIONS: A very few patients with cancer received IDDS in the US during the study period. Despite recommendations supporting its use, there are significant racial and socioeconomic disparities in IDDS use.

Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain.

Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced postsurgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals. PERSPECTIVE: This study provides a potential additional therapy to decrease postsurgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.

Lead and Pulse Generator Migration After Spinal Cord Stimulation Implantation: Insights From an Analysis of 7322 Patients.

OBJECTIVES: Lead migration (LM) after spinal cord stimulation (SCS) implantation surgery is the most common device-related complication. Our study of lead and implantable pulse generator (IPG) migration using a large administrative claims data base aims to understand rates, risk factors, and outcomes after SCS implantation. MATERIALS AND METHODS: This retrospective cohort study used the IBM® MarketScan® (Armonk, NY) Commercial and Medicare Supplemental Databases from 2016 to 2018. Adult patients who underwent SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Patients with LM and IPG migration after SCS surgery were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) codes. Patients who underwent revision surgery after SCS implantation were identified using the CPT codes and ICD-10 CM codes. In addition, patient characteristics associated with LM or IPG migration, the temporal relationship of migration diagnosis, and revision surgery were evaluated in the cohort. Continuous outcomes were compared between groups using the two-sample Student t-test. The Fisher exact test was used to compare categorical outcomes between groups. RESULTS: A total of 7322 patients (64.4% percutaneous SCS) underwent SCS surgery during the study period. A total of 141 patients (1.9%) had LM or IPG migration. Of those, 116 patients (1.6%) had LM only; 18 patients (0.2%) had IPG migration; and seven patients (0.1%) had LM and IPG migration. The mean duration for migration diagnosis after initial SCS implantation was 168 (±163.1) days. The mean duration to revision surgery after the migration diagnosis was 12.3 (±35.2) days only. Most patients with migration (105, 74.5%) underwent revision surgery. Only younger age (p = 0.02) was associated with migration in this study. CONCLUSIONS: LM and pulse generator migration that required revision surgery occurred in a small proportion of patients who underwent SCS surgical procedures.

Postoperative Oral Antibiotic Use and Infection-Related Complications After Spinal Cord Stimulator Surgery.

OBJECTIVES: Spinal cord stimulation (SCS) is considered a minimally invasive and reversible neuromodulation therapy for various chronic pain disorders. The rates of infection following SCS surgery reported in the literature range from 2.8% to 10%. Several studies indicated no potential benefit of postoperative antibiotics (beyond 24 hours) on subsequent device infection. This study aimed to understand the characteristics of postoperative antibiotic prescriptions and subsequent infections following SCS surgery. MATERIALS AND METHODS: The study was a retrospective cohort using the IBM® MarketScan® Commercial and Medicare Supplemental Databases from 2013 to 2018. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Postprocedural oral antibiotics within 14 days and preprocedural corticosteroid use within seven days were identified using National Drug Codes (NDC). Administrative claims were analyzed to understand the characteristics of prescribed postoperative antibiotics. Infection-related complications within 90 days were identified using administrative codes. RESULTS: A total of 18,105 patients (age 55.5 ± 13.1 years, 40.2% male) underwent SCS surgery during the study period. Postprocedural oral antibiotics and preprocedural steroids were prescribed for 35.3% and 2.6%, respectively, for SCS surgery patients. The most commonly used postprocedural antibiotics were cephalexin (55.4%) and sulfamethoxazole-trimethoprim (10.6%). The most common duration of antibiotic prescriptions was seven, ten, and five days in our study, from most to least common duration. Superficial surgical site infection (SSI), deep SSI, device infection, or any infection within 90 days occurred in 2.9%, 1.0%, 1.8%, and 4%, respectively, of the patients undergoing SCS surgery. CONCLUSIONS: Prospective studies are needed to understand the reasons for noncompliance with expert consensus recommendations on postoperative antibiotic use beyond 24 hours of SCS surgery. Neuromodulation team members should play an important role in antibiotic stewardship.

Procedure-Related Outcomes Including Readmission Following Spinal Cord Stimulator Implant Procedures: A Retrospective Cohort Study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to reduce opioid consumption, reduce pain, improve quality of life compared to conventional therapy, and be more effective than spine reoperation in carefully selected patients. In this study, we evaluate readmissions after SCS implantation procedures, costs, predictors, and etiologies for readmission following implantation procedures. METHODS: The study was a retrospective cohort using the National Readmissions Database from 2013 to 2017. Administrative billing codes were used to identify patients undergoing SCS implantation procedures. The primary outcome of our study was 30-day readmission following the SCS implantation procedure. Continuous outcomes were compared between groups using the Student t test or Wilcoxon rank sum test. In addition, multivariable predictors of 30-day readmission were assessed by hierarchical logistic regression analysis. RESULTS: A total of 3737 (26.7% open surgical SCS implants [OS-SCS]) individuals admitted to the hospital for SCS implantation were included in the final cohort analysis. The cohort consisted of predominantly female patients (58.71%) and in the 50- to 64-year age group (35.46%). Patients who underwent open surgical SCS implantation had a longer length of stay during the initial admission and a higher 30-day readmission rate (9.4% vs 7% P = .01). OS-SCS, older age, lower socioeconomic status, patients with specific comorbidities (ie, hypertension or chronic obstructive pulmonary disease [COPD]), and home discharge are associated with readmission. CONCLUSIONS: Readmission rates after SCS implantation are around 7.7% in the United States. Infection and postoperative complications remain the top etiologies for readmission. Open surgical SCS implantation is associated with more extended initial hospitalization and a higher rate of readmission when compared to percutaneous SCS implantation procedures.

Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation.

Benefits of phototherapy were characterized in multiple diseases including depression, circadian rhythm disruptions, and neurodegeneration. Studies on migraine and fibromyalgia patients revealed that green light-emitting diodes (GLED) exposure provides a pragmatic and safe therapy to manage chronic pain. In rodents, GLED reversed hypersensitivity related to neuropathic pain. However, little is known about the underlying mechanisms of GLED efficacy. Here, we sought to understand how green light modulates the endogenous opioid system. We first characterized how exposure to GLED stimulates release of ß-endorphin and proenkephalin in the central nervous system of male rats. Moreover, by individually editing each of the receptors, we found that µ- and δ-opioid receptors are required for green light's antinociceptive effect in naïve rats and a model of HIV-induced peripheral neuropathy. We investigated how GLED could increase pain thresholds, and explored its potential in reversing hypersensitivity in a model of HIV-related neuropathy. Through behavioral and gene editing approaches, we identified that green light provides antinociception via modulation of the endogenous opioid system in the spinal cord. This work identifies a previously unknown mechanism by which GLED can improve pain management. Clinical translation of these results will advance the development of an innovative therapy devoid of adverse effects. PERSPECTIVE: Development of new pain management therapies, especially for HIV patients, is crucial as long-term opioid prescription is not recommended due to adverse side effects. Green light addresses this necessity. Characterizing the underlying mechanisms of this potentially groundbreaking and safe antinociceptive therapy will advance its clinical translation.

Evaluating the efficacy of nitazoxanide in uncomplicated amebic liver abscess.

BACKGROUND: Amebic liver abscess is treated successfully with metronidazole or another nitroimidazole drug followed by a luminal amebicide. Metronidazole has long been preferred, but has been associated with several adverse effects including intolerance in certain clinical situations. Mechanisms of metronidazole resistance and mutagenic potential have been described. Effects of the use of drug in pregnant women and infants of lactating women are unknown. Nitazoxanide was proven to be efficacious in treating invasive intestinal amebiasis. Therefore, the present study was undertaken to assess the efficacy and safety of nitazoxanide as compared to metronidazole in patients with uncomplicated amebic liver abscess. METHODS: Patients with clinical and ultrasonography features suggestive of liver abscess, positive amebic serology, and/or anchovy sauce appearance on aspiration of the pus were included in the study and randomized into two parallel treatment groups. Group M received metronidazole, 2-2.5 g/day intravenous (IV), for inpatients, or 2-2.4 g/day oral, for outpatients in three divided doses for 14 days. Group N received nitazoxanide 500 mg BD per oral for 10 days. RESULTS: A total of sixty subjects fulfilling the inclusion criteria were randomized equally into two groups, group M and group N. Number of patients achieving symptomatic clinical response (SCR) was similar in the two groups (80% vs. 76.7%, p = 1.00), though time to achieve symptomatic clinical response was significantly lower in metronidazole group as compared to that in nitazoxanide group. Greater proportion of patients achieved early clinical response (ECR) in metronidazole group as compared to nitazoxanide group. Complete resolution of abscess, at 6 months, was noted in 18 (60%) patients in the M group and 22 (73.3%) patients in the N group (p = 0.273). Metronidazole was associated with significantly greater frequency of adverse effects than nitazoxanide. CONCLUSIONS: This study shows equivalent efficacy of nitazoxanide in uncomplicated amebic liver abscess as compared to metronidazole, with better tolerability and advantage of simultaneous luminal clearance, thus reducing chances of recurrence. TRIAL REGISTRATION: CTRI/2019/01/017249.

Industry Payments to Pain Medicine Physicians: An Analysis of the Centers for Medicare and Medicaid Services Open Payments Program.

OBJECTIVE: To analyze industry payments to pain medicine physicians in the United States. DESIGN: Retrospective cohort study using publicly available databases. SUBJECTS: The study includes U.S. pain medicine physicians (PMPs) with reports in the Open Payments program from 2013 to 2018. METHODS: The Centers for Medicare and Medicaid Services Open Payments program was analyzed for general, investment, and ownership payments to PMPs reported from 2013 to 2018. The nature, type, and geographic variation of payments were analyzed. RESULTS: The main findings of the study are as follows: 1) Payments made to PMPs constituted a small proportion of the payments made to all physicians in the United States, and the number of transactions and the total dollar amount seem to have decreased from 2016 to 2018. 2) The median number of payments among physicians with reported payments was around 4 (interquartile range: 18), and the majority of them were under $20. 3) The majority of payments were for in-kind items and services (85%) and were made for food and beverages (91%), travel and lodging (5.5%). 4) Some of the ownership and investment interest payments exceeded $500,000. 5) The top five drugs associated with physician payments included medications with opioids. 6) A very small minority of payments were made for entertainment or gifts. 7) A third of PMPs with reports had payments reported under more than one taxonomy. CONCLUSIONS: Overall payments made to PMPs seem to be decreasing since 2016. The majority of the payments are made for the food, beverage, and travel categories. Public and physician awareness of the Open Payments system reports is essential to promote transparency and to minimize adverse effects of financial relationships on patient care.

Opioid Prescriptions by Pain Medicine Physicians in the Medicare Part D Program: A Cross-Sectional Study.

BACKGROUND: Pain medicine physicians (PMP) are a group of physicians with background training in various primary specialties with interest and expertise in managing chronic pain disorders. Our objective is to analyze prescription drug (PD) claims from the Medicare Part D program associated with PMP to gain insights into patterns, associated costs, and potential cost savings areas. METHODS: The primary data source for Part D claims data is the Centers for Medicare and Medicaid Services (CMS) Chronic Conditions Data Warehouse, which contains Medicare Part D prescription drug events (PDE) records received through the claims submission cutoff date. Only providers with taxonomies of pain management (PM) and interventional pain management (IPM) were included in the study. The analysis of PDE was restricted to drugs with >250 claims. The distribution of claims and costs were analyzed based on drug class and provider specialty. Subsequently, we explored claims and expenses for opioid drug prescriptions in detail. Prescribing characteristics of the top 5% of providers by costs and claims were examined to gain additional insights. The costs and claims were explored for the top 10 drugs prescribed by PMP in 2017. RESULTS: There were a total of unique 3280 PMP-prescribed drugs with an associated expense of 652 million dollars in the 2017 Medicare Part D program. Prescriptions related to PMP account for a tiny fraction of the program's drug expenditure (0.4%). Opioids, anticonvulsants, and gabapentinoids were associated with the largest number of claims and the largest expenses within this fraction. Among opioid drug prescriptions, brand-named drugs account for a small fraction of claims (8%) compared to generic drugs. However, the expenses associated with brand name drugs were higher than generic drugs. Prescribers in the top 5% by PD costs had a higher number of claims, prescribed a higher proportion of branded medications, and had prescriptions associated with longer day supply compared to an average PMP. There were several opioid medications in the top 10 PD list by cost associated with PMP. CONCLUSIONS: Opioids were the most common medications among Medicare part D claims prescribed by PMP. Only 12% of the total opioid PD claims were by PMP. The top 5% of PMP prescribers had 10 times more claims than the average PMP.

Liposomal bupivacaine during subcutaneous implantable cardioverter defibrillator implantation for pain management.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has a larger generator and its implantation involves more dissection and tunneling compared to traditional transvenous defibrillator system. Liposomal bupivacaine, an extended-release bupivacaine with 72 h of duration has been used for postoperative pain management in patients undergoing S-ICD implantation. Our aim was to compare postoperative pain and opioid prescription patterns among patients undergoing S-ICD implantation who received intraprocedural liposomal bupivacaine and those who did not. METHODS: We performed a retrospective analysis of all patients who underwent subcutaneous ICD implantation from January 1, 2013 to March 30, 2018 at the Mayo Clinic in Rochester, Minnesota. Patients were categorized into those who received liposomal bupivacaine and those who did not. Data on inpatient pain score, outpatient opioid prescription rates at discharge, and doses based on oral morphine equivalents (OME) were collected. RESULTS: A total of 104 patients underwent S-ICD implantation. Intraprocedural liposomal bupivacaine was used in 69% of patients. Patients who received intraprocedural liposomal bupivacaine had similar mean inpatient pain scores (2.9 vs. 2.9, p = .786). There was also no difference in the rate of inpatient opioid administration (79.2% vs. 87.5%, p = .4139), outpatient opioid prescription (23.6% vs. 12.5%, p = .29), or mean OME (41.7-mg vs. 16.6-mg, p = .188) when comparing patients those who received intraprocedural liposomal bupivacaine and those who did not. CONCLUSION: Intraprocedural liposomal bupivacaine administration was not associated with any significant impact on postoperative pain scores, inpatient opioid administration, and outpatient opioid prescription rates or OME amounts at discharge.

Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial.

BACKGROUND: Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine. MATERIAL AND METHODS: We recruited (29 total) patients, of whom seven had episodic migraine and 22 had chronic migraine. We used a one-way cross-over design consisting of exposure for 1-2 hours daily to white light emitting diodes for 10 weeks, followed by a 2-week washout period followed by exposure for 1-2 hours daily to green light emitting diodes for 10 weeks. Patients were allowed to continue current therapies and to initiate new treatments as directed by their physicians. Outcomes consisted of patient-reported surveys. The primary outcome measure was the number of headache days per month. Secondary outcome measures included patient-reported changes in the intensity and frequency of the headaches over a two-week period and other quality of life measures including ability to fall and stay asleep, and ability to perform work. Changes in pain medications were obtained to assess potential reduction. RESULTS: When seven episodic migraine and 22 chronic migraine patients were analyzed as separate cohorts, white light emitting diodes produced no significant change in headache days in either episodic migraine or chronic migraine patients. Combining data from the episodic migraine and chronic migraine groups showed that white light emitting diodes produced a small, but statistically significant reduction in headache days from (days ± SEM) 18.2 ± 1.8 to 16.5 ± 2.01 days. Green light emitting diodes resulted in a significant decrease in headache days from 7.9 ± 1.6 to 2.4 ± 1.1 and from 22.3 ± 1.2 to 9.4 ± 1.6 in episodic migraine and chronic migraine patients, respectively. While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes. Conclusions regarding pain medications reduction with green light emitting diode exposure were not possible. No side effects of light therapy were reported. None of the patients in the study reported initiation of new therapies. DISCUSSION: Green light emitting diodes significantly reduced the number of headache days in people with episodic migraine or chronic migraine. Additionally, green light emitting diodes significantly improved multiple secondary outcome measures including quality of life and intensity and duration of the headache attacks. As no adverse events were reported, green light emitting diodes may provide a treatment option for those patients who prefer non-pharmacological therapies or may be considered in complementing other treatment strategies. Limitations of this study are the small number of patients evaluated. The positive data obtained support implementation of larger clinical trials to determine possible effects of green light emitting diode therapy.This study is registered with clinicaltrials.gov under NCT03677206.

Outcomes Associated With Infection of Chronic Pain Spinal Implantable Electronic Devices: Insights From a Nationwide Inpatient Sample Study.

OBJECTIVES: Chronic pain spinal implantable electronic devices (CPSIEDs) include devices that provide spinal cord stimulation and intrathecal drug therapy. In this study, we sought to evaluate the trends of CPSIED infections, related complications, and outcomes following the treatment of infection. MATERIALS AND METHODS: The Nationwide Inpatient Sample database contains data from 48 states, and the District of Columbia was used to identify patients with a primary diagnosis of CPSIED infection during the years 2005-2014. Patients with intrathecal pumps for the treatment of spasticity were excluded to limit the study population to patients with chronic pain disorders. Treatments were categorized as: 1) without device removal, 2) pulse generator or pump only removal, 3) intrathecal pump system removal, and 4) spinal cord stimulation system removal. Complications associated with CPSIED infections were identified using administrative billing codes. RESULTS: During the study period 2005-2014, a total of 11,041 patients were admitted to the hospital with CPSIED infections. The majority of the patients were treated without surgical intervention (56%), and a smaller proportion underwent complete system explantation (22.7%). In-hospital mortality or permanent disability due to paralysis after CPSIED infection was around 1.83% and 2.77%, respectively. Infectious complications such as meningitis, abscess formation, and osteomyelitis occurred in 4.93%, 5.08%, and 1.5%, respectively. The median cost of hospitalization was around US $14,118.00, and the median length of stay was approximately six days (interquartile range = 4-13 days). CONCLUSIONS: The complications of CPSIED infection were higher among patients that did not undergo device removal.

Personalizing Dual-Target Cortical Stimulation with Bayesian Parameter Optimization Successfully Treats Central Post-Stroke Pain: A Case Report.

Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.

Adverse Events and Complications Associated With Intrathecal Drug Delivery Systems: Insights From the Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND: Modern intrathecal drug delivery systems (IDDS) are technologically advanced to deliver medication through various automated and patient-controlled programs. They also are associated with unique complications ranging from post-operative complications, medication-related adverse events (AE), device malfunction, to refill associated AE. OBJECTIVES: To systematically analyze real-world complications and AE reported on the Food and Drug Administration's Manufacturer and User Facility Device Experience database (MAUDE) associated with IDDS among patients predominantly with chronic pain disorders. MATERIALS AND METHODS: MAUDE database was sampled for a month four times a year during the study period, February 2018 to February 2019. The database was resampled every six months till August 2020 to evaluate for any additional reported cases during the index months. The two FDA approved IDDS, were included. AE were broadly classified into causes related to catheter malfunction, pump malfunction, biologic, and medication-related AE. RESULTS: A total of 1001 reports were included in the final analysis. The top three reasons for adverse report are infection/erosion (15.7%, n = 157), motor stall (12.4%, n = 125) and adverse medication reactions (11.8%, n = 119), respectively. There were five deaths among patients with IDDS. Epidural hematoma (n = 3) after IDDS surgery resulted in a death and residual neurological deficits after surgical evacuation. Programming errors, medication concentration discrepancy, and failure to turn on the pump after reprogramming are various preventable causes of medication-related IDDS AEs. CONCLUSIONS: Analysis of AE associated with IDDS from the MAUDE database provided a real-world perspective different from reported registry complications. Awareness and vigilance of preventable IDDS-related complications is the first step toward mitigating risks to provide safe and effective intrathecal drug delivery for chronic pain management.

Green Light Exposure Improves Pain and Quality of Life in Fibromyalgia Patients: A Preliminary One-Way Crossover Clinical Trial.

OBJECTIVE: Fibromyalgia is a functional pain disorder in which patients suffer from widespread pain and poor quality of life. Fibromyalgia pain and its impact on quality of life are not effectively managed with current therapeutics. Previously, in a preclinical rat study, we demonstrated that exposure to green light-emitting diodes (GLED) for 8 hours/day for 5 days resulted in antinociception and reversal of thermal and mechanical hypersensitivity associated with models of injury-related pain. Given the safety of GLED and the ease of its use, our objective is to administer GLED as a potential therapy to patients with fibromyalgia. DESIGN: One-way crossover clinical trial. SETTING: United States. METHOD: We enrolled 21 adult patients with fibromyalgia recruited from the University of Arizona chronic pain clinic who were initially exposed to white light-emitting diodes and then were crossed over to GLED for 1 to 2 hours daily for 10 weeks. Data were collected by using paper surveys. RESULTS: When patients were exposed to GLED, but not white light-emitting diodes, they reported a significant reduction in average pain intensity on the 10-point numeric pain scale. Secondary outcomes were assessed by using the EQ-5D-5L survey, Short-Form McGill Pain Questionnaire, and Fibromyalgia Impact Questionnaire and were also significantly improved in patients exposed to GLED. GLED therapy was not associated with any measured side effects in these patients. CONCLUSION: Although the mechanism by which GLED elicits pain reduction is currently being studied, these results supporting its efficacy and safety merit a larger clinical trial.