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Abstract Introduction Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. Methods A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS—needle electrodes) and transcutaneous (tVNS—surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. Results A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges’ g/mean difference of − 1.95 (95% confidence interval [CI]: − 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (− 5.40 [− 8.94; − 1.85] vs. − 1.00 [− 1.55; − 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with − 0.70 [− 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. Conclusion This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

ABSTRACT: Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%–90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23–6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

Abstract Background Lumbar foraminal stenosis is a common cause of chronic lower back pain and radiculopathy often treated by epidural steroid injections. In the absence of imaging findings with a positive physical exam demonstrating symptoms, percutaneous neuroplasty (PNP) may be an alternative to transforaminal epidural steroid injections that have otherwise failed. Case Presentation We present two cases (55-year-old man and 65-year-old woman) with chronic low back pain and radiculopathy with otherwise normal imaging demonstrating no lumbar foraminal stenosis refractory to transforaminal epidural steroid injections. PNP was performed using reference spinal needles with both patients achieving sustained > 50–75% pain relief. Conclusion PNP offers interventional chronic pain physicians and patients with refractory chronic low back pain with lumbar radiculopathy due to fibrosis an alternative, safe treatment that offers sustained results. Furthermore, this is the first of its kind to offer a step-by-step procedural step of PNP using a reference spinal needle.

Abstract. Introduction:. Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention. Objectives:. To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool. Methods:. This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis. Results:. The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a “leave-one-out” analysis (all P < 0.001). Conclusion:. The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions.

AbstractComplex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Abstract Introduction Sacroiliac joint (SIJ) pain is a relatively common cause of low back pain. Percutaneous radiofrequency (RF) techniques for SIJ are limited to ablation of the posterior SIJ innervation. Different techniques have been described for SIJ radiofrequency ablation, including conventional thermal, cooled RF, pulsed RF, bipolar RF, and specialized tip RF needle (i.e., multi-tined); however, additional costs may limit these applications. Methods This new technique for SIJ denervation uses anatomical landmarks and a single RF cannula. Two spinal needles are placed lateral to the posterior S1 and S2 sacral foramina; then, with caudal tilt we get a coaxial view of the sacral bone, we advance an 18-G curved 15-mm active tip RF cannula just lateral to the aligned finder needles. Ablation is performed, and then the RF cannula is retracted 2 cm and ablation is repeated for a total of four lesions. Results The two spinal needles placed lateral to the posterior sacral foramina S1 and S2 guide the final needle in the posterior aspect of the sacrum, lateral to the sacral foramina, where the lateral sacral branches are located. Conclusion We introduce a cost and time efficient technique to perform radiofrequency ablation of the sacral lateral branches using a single RF needle. This technique utilizes the sacrum’s reliable anatomy and angulation and maximizes the surface area of the active tip lesioning. This technique creates a strip lesion lateral to the sacral foramina and reduces time and cost efficacy compared to several of the other techniques and/or commercially available special devices designed for sacroiliac denervation.

Chronic low back pain (CLBP) negatively impacts quality of life and contributes to a significant economic burden. One conservative management strategy for CLBP is lumbar back bracing. Despite the benefits of back bracing for improving pain and function, there remains hesitance to use the therapy long term due to unfounded fear related to muscle weakness, deconditioning, or joint contracture. Objective: The purpose of this study was to examine the outcomes for patients with CLBP who were managed with lumbar back bracing and physical therapy. Methods: This was a single-site, retrospective chart review. Results: Patients were included in the study if they were treated for CLBP with back bracing for at least one hour daily and physical therapy for twelve weeks. Pain was assessed at three, six, and twelve months using the 11-point Visual Analogue Scale (VAS). Function was assessed at three months using the Oswestry Disability Index (ODI). The VAS score reduced from 6.28 +/− 2.32 to 3.96 +/− 2.66 at three months (p < 0.001) for 198 patients. At six and twelve months, the VAS score reduced to 3.74 +/− 2.73 (p < 0.001) and 3.23 +/− 2.29 (p < 0.001), respectively. The total ODI score for 199 patients improved from 46.56 +/− 15.30 to 33.13 +/− 19.99 (p < 0.001) at three months. Conclusion: Back bracing in combination with physical therapy is effective for treating low back pain.

Introduction: Knee osteoarthritis (OA) is a highly prevalent and debilitating condition with significant emotional and economic impacts. Current treatment options may only provide temporary pain relief and are not regenerative, thus the progression of knee OA is not deterred and total knee arthroplasty is inevitable. Injection therapies with orthobiologics possess regenerative potential and are an emerging treatment option. We present a prospective study aimed at examining patients with knee OA who had received an autologous platelet concentrate fluid (APCF) injection produced through a fluid volume reducer. Methods: This was an observational review of the results following an APCF injection in a cohort of patients at a single site. Patients were included in the study if they were diagnosed with K/L grade 2–3 knee OA and treated with an APCF knee injection. Patients were excluded if they had obtained an orthobiologic injection in the three months prior to study enrollment or if baseline data were unavailable. Knee score and function score were used to assess patients at the baseline and post-injection follow-ups. Results: Improvements for knee score were statistically significant for the follow-ups at three months, six months, one year, and three years. Function score improved, with statistically significant changes for the three month and three year follow-ups. Conclusions: Our study demonstrates that there is some utility in using APCF injection for knee OA, with improvements that may be sustained up to three years in some patients.

Abstract Introduction Chronic pain is a growing problem across the world, and in the midst of an opioid epidemic, it is imperative that alternative treatment measures are identified to help alleviate the pain experienced by these patients. Chronic pain greatly affects ones quality of life and many patients do not experience adequate relief with conventional treatment measures. The purpose of this retrospective analysis is to assess the efficacy of peripheral nerve stimulation (PNS) therapy in adult patients suffering from chronic pain refractory to conventional treatment measures who underwent therapy on various anatomical locations. Methods This retrospective analysis consisted of data collected from electronic health records for n = 89 patients who underwent PNS therapy. Data collected relates to patient age, sex, weight, height, body mass index (BMI), diagnosis, targeted nerves, follow-up encounters, pain scores from before and after PNS therapy, and duration of improvement. Statistical analysis used SPSS software, version 26 (IBM), using a paired t test to assess significance between pre and post PNS therapy pain scores. P values were significant if found to be ≤ 0.05. Further analysis assessed the correlation between age and BMI with visual analog scale (VAS) pain improvement and subjective percentage pain relief. Results The mean pre-operative (pre-op) pain score before PNS therapy was 6.36 (standard deviation (SD) = 2.18, SEM = 0.23) and the mean post-operative (post-op) pain score after PNS therapy was 4.19 (SD = 2.70, SEM = 0.29). The mean patient-reported percent improvement in pain following PNS therapy was 49.04% (SD = 34.79). The improvement in pain scores between pre-op and post-op was statistically significant (M = 2.17, SD = 2.82, SEM = 0.30, t(88) = 7.26, p

Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management—namely duloxetine, milnacipran, pregabalin, and amitriptyline—which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.

Neuromodulation is an alternative, minimally invasive treatment option that, at times, is used as a last resort for chronic pain conditions that are often refractory to other treatment modalities. Moreover, it offers promising prospects for individuals grappling with the formidable challenges posed by paraplegia and quadriplegia resulting from spinal cord injuries. This review article provides a comprehensive assessment of current treatment modalities specifically tailored for paraplegic and quadriplegic patients. We aim to evaluate the existing surgical and non-surgical interventions while delving into the role of neuromodulation in the restoration of function for individuals afflicted with these debilitating conditions. Additionally, we review the efficacy, limitations, and comparative outcomes of diverse treatment strategies available for the management of paraplegia and quadriplegia. Emphasizing the critical need for effective interventions beyond the initial 24 h surgical window, we elucidate the challenges associated with conventional therapies and their limited success in achieving comprehensive functional restoration. Central to this review is an in-depth exploration of neuromodulation’s transformative potential in ameliorating the deficits caused by spinal cord injuries. With a particular focus on spinal cord stimulation (SCS), we analyze and compare the outcomes of neuromodulation modalities and traditional treatment regimens, shedding light on the promising strides made in fostering sensory perception, motor function, and patient satisfaction.

Abstract Introduction The peripheral nervous system is an increasingly popular target for chronic pain treatment modalities. Noninvasive neuromodulation has shown promise at providing significant chronic pain relief with a much safer side effect profile. This retrospective pilot study is shaped around a noninvasive neuromodulation system over a 2-week treatment timeline. Methods Open-label survey of chronic pain patients recruited from Veteran Affairs, orthopedic, and pain health systems. If a noninvasive neuromodulation system was prescribed the patients were then offered a 2-week follow-up survey. This voluntary survey did not affect their therapy duration or quality. This survey was designed to address similar metrics as smaller noninvasive neuromodulation studies to allow a quality comparison while giving more power with a large population size of 1511 patients. Overall pain scores (including before and after scores), satisfaction level, desire to continue therapy, medication use, effect on functional metrics (mood, sleep, sit, stand, walk, and lift), and activities of daily living (ADL) scores were assessed. Results The results demonstrated an overall pain reduction of 46%. All functional metrics were improved throughout with the largest improvements reported in mood and sleep at over 47%. Medication use was reported as decreased or eliminated in 42% of patients. There were no adverse reactions or complications reported over the 1511 patients. Conclusion This survey is amongst the largest population sizes every studied for noninvasive neuromodulation. Within just 2 weeks patients can see a reduction in overall pain and medication needs. Although survey studies have inherent limitations such as duration and compliance biases with such an overwhelming benefit in every category we believe that noninvasive neuromodulation therapy is a promising, safe, and cost-effective therapy. Future studies should focus on long-term follow-ups and post-therapy pain scores with a placebo group.

Abstract Chronic pain is a debilitating condition with a growing prevalence both in the USA and globally. The complex nature of this condition necessitates a multimodal approach to pain management that extends beyond the established pharmaceutical interventions currently employed. A variety of devices comprising both invasive and noninvasive approaches are available to patients, serving as adjuvants to existing regimens. The benefits of these interventions are notable for their lack of addiction potential, potential for patient autonomy regarding self-administration, minimal to no drug interaction, and overall relative safety. However, there remains a need for further research and more robust clinical trials to assess the true efficacy of these interventions and elucidate if there is an underlying physiological mechanism to their benefit in treating chronic pain or if their effect is predominantly placebo in nature. Regardless, the field of device-based intervention and treatment remains an evolving field with much promise for the future chronic pain management.

This narrative review aims to summarize evidence regarding the current utilization and future applications of neuromodulation in patients with headaches, with special attention paid to migraine and chronic cluster headache. A search was conducted in PubMed in August of 2023 to survey the current literature on neuromodulation for the treatment of headache. In total, the search yielded 1989 results, which were further filtered to include only systematic reviews published between 2022 to 2023 to capture the most up-to-date and comprehensive research on this topic. The citation lists of these articles were reviewed to find additional research on neuromodulation and supplement the results presented in this paper with primary literature. Research on the use of neuromodulation for the treatment of headache has predominantly focused on four neuromodulation techniques: peripheral nerve stimulation (PNS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and spinal cord stimulation (SCS). Outcome measures reported in this article include impact on migraine and headache frequency and/or pain intensity, adverse effects of the neuromodulation technique, and associated costs, when available. We found that neuromodulation has developed utility as an alternative treatment for both chronic cluster headaches and migraines, with a reduction in frequency and intensity of headache most elucidated from the articles mentioned in this review.

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices’ often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were offered for patients to use daily at-home for one week to assess the durability of sham placebo effects before participants were given active treatment in a second office visit followed by another optional week of self-administered active treatment at-home use. Sham treatments reduced pain scores by an average of 31% from 6.0 ± 2.3 to 4.3 ± 3.3, including two participants who fell asleep during the in-office treatment and woke up with no pain, but whose pain recurred after returning home during at-home use of the sham system. In-office active treatments reduced pain scores by 52% from 6.7 ± 2.1 to 3.3 ± 2.9 with sustained pain relief during optional at-home use. Successful blinding for the study was confirmed with an ideal Bang’s Blinding Index of 0 and an ideal James’ Blinding Index of 1. Both the sham and active treatments were viewed by participants as highly credible, and credibility increased from the beginning to end of sham treatments on average.

Headaches and facial pain are highly prevalent diseases but are often difficult to treat. Though there have been significant advances in medical management, many continue to suffer from refractory pain. Neuromodulation has been gaining interest for its therapeutic purposes in many chronic pain conditions, including headaches and facial pain. There are many potential targets of neuromodulation for headache and facial pain, and some have more robust evidence in favor of their use than others. Despite the need for more high-quality research, the available evidence for the use of neuromodulation in treating headaches and facial pain is promising. Considering the suffering that afflicts patients with intractable headache, neuromodulation may be an appropriate tool to improve not only pain but also disability and quality of life.

# Purpose of Review Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials. # Recent Findings Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory to conventional treatment. A meta-analysis in 2016 showed that brivaracetam as adjunctive therapy was statically significant in its reduction of adults with drug-refractory seizure frequency.^1^ The most commonly reported adverse effects that patients who were taking brivaracetam experienced were somnolence, headache, and dizziness. Further studies are necessary to conclude long term efficacy and safety profile of brivaracetam. # Conclusion The treatment of epilepsy with pharmacologic agents is a difficult task due to balancing the efficacy of the drug with the side effect profile that will allow for the best quality of life for the patient. There are approximately 30 antiepileptic agents for clinicians to choose from. Brivaracetam is a novel antiepileptic agent that was approved for use by the FDA in 2016 and is showing promising results as monotherapy and adjunctive therapy in individuals with drug-refractory focal seizures while minimizing adverse drug reactions.

Neuromodulation, through the use of spinal cord stimulation, is an evolving therapeutic alternative for the management of chronic and refractory pain [...]

Objective: The objective of this study was to evaluate discrepancies in prescription trends for analgesic medications in complex regional pain syndrome (CRPS) patients based on recommendations in the literature. Design: We conducted a retrospective case–control study. Subjects: A total of 2510 CRPS patients and 2510 demographic-matched controls participated in this study. Methods: The SlicerDicer feature in Epic was used to find patients diagnosed with CRPS I or II between January 2010 and November 2022. An equal number of age-, gender-, and race-matched controls without a CRPS diagnosis were retracted from Epic. General and CRPS-associated prescription frequencies for the following classes were retrieved for both cases and controls: benzodiazepines, bisphosphonates, calcitonin, capsaicin, neuropathic pain medications, NSAIDs, opioids, and steroids. Results: A total of 740 (29%) CRPS patients and 425 (17%) controls were prescribed benzodiazepines (95% CI 0.1–0.15), 154 (6.1%) CRPS patients and 52 (2.1%) controls were prescribed capsaicin (95% CI 0.03–0.05), 1837 (73%) CRPS patients and 927 (37%) controls were prescribed neuropathic pain medications (95% CI 0.05–0.34), 1769 (70%) CRPS patients and 1217 (48%) controls were prescribed opioids (95% CI 0.19–0.25), 1095 (44%) CRPS patients and 1217 (48%) controls were prescribed steroids (95% CI 0.08–0.14), and 1638 (65%) CRPS patients and 1765 (70%) controls were prescribed NSAIDs (95% CI −0.08–0.02), p < 0.001 for all classes. With CRPS-associated prescriptions, (95% CI 0.05–0.16, p < 0.001) more CRPS patients were prescribed opioids (N = 398, 59%) than controls (N = 327, 49%). Conclusions: CRPS is difficult to treat with significant variance in suggested treatment modalities. Based on the results of our study, there is a divergence between some published recommendations and actual practice.

Work-related injuries are common. The cost of these injuries is around USD 176 billion to USD 350 billion a year. A significant number of work-related injuries involve nerve damage or dysfunction. Injuries may heal with full recovery of function, but those involving nerve damage may result in significant loss of function or very prolonged recovery. While many factors can predispose a person to suffer nerve damage, in most cases, it is a multifactorial issue that involves both intrinsic and extrinsic factors. This makes preventing work-related injuries hard. To date, no evidence-based guidelines are available to clinicians to evaluate work-related nerve dysfunction. While the symptoms range from poor endurance to cramping to clear loss of motor and sensory functions, not all nerves are equally vulnerable. The common risk factors for nerve damage are a superficial location, a long course, an acute change in trajectory along the course, and coursing through tight spaces. The pathophysiology of acute nerve injury is well known, but that of chronic nerve injury is much less well understood. The two most common mechanisms of nerve injury are stretching and compression. Chronic mild to moderate compression is the most common mechanism of nerve injury and it elicits a characteristic response from Schwann cells, which is different from the one when nerve is acutely injured. It is important to gain a better understanding of work-related nerve dysfunction, both from health and from regulatory standpoints. Currently, management depends upon etiology of nerve damage, recovery is often poor if nerves are badly damaged or treatment is not instituted early. This article reviews the current pathophysiology of chronic nerve injury. Chronic nerve injury animal models have contributed a lot to our understanding but it is still not complete. Better understanding of chronic nerve injury pathology will result in identification of novel and more effective targets for pharmacological interventions.

While denervation can occur with aging, peripheral nerve injuries are debilitating and often leads to a loss of function and neuropathic pain. Although injured peripheral nerves can regenerate and reinnervate their targets, this process is slow and directionless. There is some evidence supporting the use of neuromodulation to enhance the regeneration of peripheral nerves. This systematic review reported on the underlying mechanisms that allow neuromodulation to aid peripheral nerve regeneration and highlighted important in vivo studies that demonstrate its efficacy. Studies were identified from PubMed (inception through September 2022) and the results were synthesized qualitatively. Included studies were required to contain content related to peripheral nerve regeneration and some form of neuromodulation. Studies reporting in vivo highlights were subject to a risk of bias assessment using the Cochrane Risk of Bias tool. The results of 52 studies indicate that neuromodulation enhances natural peripheral nerve regeneration processes, but still requires other interventions (e.g., conduits) to control the direction of reinnervation. Additional human studies are warranted to verify the applicability of animal studies and to determine how neuromodulation can be optimized for the greatest functional restoration.

Abstract Introduction Radiofrequency ablation (RFA) is an interventional procedure that provides pain relief by using thermal energy to disrupt peripheral nerves carrying nociceptive signals back to the central nervous system. In the past, having implantable hardware at the planned site of RFA was considered to confer increased risk of adverse outcomes given the theoretical risk of heating of the hardware components. The present study examines patient outcomes to determine whether the efficacy of RFA was affected by the presence of implanted hardware directly at the site. Methods This was a retrospective case–control study that included 52 patients who received RFA procedures in the presence of hardware at the site of RFA and a control group of 170 patients who received RFA procedures in the absence of hardware. Data were collected from electronic medical records entered into an Excel sheet and then analyzed using SPSS version 22. Outcomes tested included post procedure pain scores, percent, and duration of improvement, if any. Results We found no statistically significant difference in measured outcomes between either group. Conclusions This study provides some evidence in support of the theory that RFA procedures performed on patients with pre-existing hardware have similar efficacy when compared to their hardware-free counterparts.

Abstract Background Peripheral Nerve Stimulation has been used to treat human disease including pain for several decades. Innovation has made it a more viable option for treatment of common chronic pain processes, and interest in the therapy is increasing. Main body While clinical data is forthcoming, understanding factors that influence successful outcomes in the use of PNS still needs to be delineated. This article reviews the evolution and bioelectronic principles of peripheral nerve stimulation including patient selection, nerve targets, techniques and guidance of target delivery. We collate the current evidence for outcomes and provide recommendations for salient topics in PNS. Conclusion Peripheral nerve stimulation has evolved from a surgically invasive procedure to a minimally invasive technique that can be used early in the treatment of peripheral nerve pain. This review identifies and addresses many of the variables which influence the success of PNS in the clinical setting.

Abstract Purpose of Review This is a comprehensive literature review of the available evidence and techniques of foot injections for chronic pain conditions. It briefly describes common foot chronic pain syndromes and then reviews available injection techniques for each of these syndromes, weighing the available evidence and comparing the available approaches. Recent Findings Foot and ankle pain affects 20% of the population over 50 and significantly impairs mobility and ability to participate in activities of daily living (ADLs), as well as increases fall risk. It is commonly treated with costly surgery, at times with questionable efficacy. Injection therapy is challenging when the etiology is anatomical or compressive. Morton’s neuroma is a budging of the interdigital nerve. Steroid, alcohol, and capsaicin injections provide some benefit, but it is short lived. Hyaluronic acid (HA) injection provided long-term relief and could prove to be a viable treatment option. Achilles tendinopathy (AT) is most likely secondary to repeat tendon stress—platelet-rich-plasma (PRP) and prolotherapy have been trialed for this condition, but more evidence is required to show efficacy. Similar injections were trials for plantar fasciitis and achieved only short-term relief; however, some evidence suggests that PRP injections reduce the frequency of required therapy. Tarsal tunnel syndrome, a compressive neuropathy carries a risk of permanent neural injury if left untreated. Injection therapy can provide a bridge to surgery; however, surgical decompression remains the definitive therapy. When the etiology is inflammatory, steroid injection is more likely to provide benefit. This has been shown in several studies for gout, as well as osteoarthritis of the foot and ankle and treatment-refractory rheumatoid arthritis. HA showed similar benefit, possibly due to anti-inflammatory effects. Stem cell injections may provide the additional benefit of structure restoration. Summary Chronic foot pain is common in the general population and has significant associated morbidity and disability. Traditionally treated with surgery, these are costly and only somewhat effective. Injections provide an effective alternative financially and some evidence exists that they are effective in pain alleviation. However, current evidence is limited and the benefit described from injection therapy has been short-lived in most cases. Further studies in larger populations are required to evaluate the long-term effects of these treatments.

Abstract Introduction This compilation presents a comprehensive review of the literature on common chronic pain conditions of the hand. It briefly presents these common conditions with their biological background, diagnosis, and common management options. It then presents and compares the latest literature available for injection techniques to treat these diagnoses and compares the available evidence. Methods A comprehensive literature review was performed in MEDLINE, PubMed, and Cochrane databases from 1996 to 2019 using the terms “hand pain”, “injection techniques”, “steroid injection”, “chronic pain”, “osteoarthritis”, “rheumatoid arthritis”, “carpal tunnel syndrome”, “De Quervain’s tenosynovitis”, “ganglion cyst”, “gout”, “Raynaud’s”, and “stenosing tenosynovitis”. Results Hand pain is a common condition with 9.7% prevalence in men and 21.6% in women and can cause significant morbidity and disability. It also carries a significant cost to the individuals and the healthcare system, totaling in $4 billion dollars in 2003. Injection therapy is an alternative when conservative treatment fails. Osteoarthritis is the most common chronic hand pain syndrome and affects about 16% of the population. Its mechanism is largely mechanic, and as such, there is controversy if steroid injections are of benefit. Hyaluronic acid (HA) appears to provide substantial relief of pain and may increase functionality. More studies of HA are required to make a definite judgment on its efficacy. Similarly, steroid ganglion cyst injection may confer little benefit. Carpal tunnel syndrome is a compressive neuropathy, and only temporarily relieved with injection therapy. US-guidance provides significant improvement and, while severe cases may still require surgery, can provide a valuable bridge therapy to surgery when conservative treatment fails. Similar bridging treatments and increased efficacy under US-guidance are effective for stenosing tenosynovitis (“trigger finger”), though, interestingly, inflammatory background is associated with decreased effect in this case. When the etiology of the pain is inflammatory, such as in RA, corticosteroid (CS) injections provide significant pain relief and increased functionality. They do not, however, change the course of disease (unlike DMARDs). Another such example is De-Quervain tenosynovitis that sees good benefit from CS injections, and an increased efficacy with US-guidance, and similarly are CS injections for gout. For Raynaud’s phenomenon, Botox injections have encouraging results, but more studies are needed to determine safety and efficacy, as well as the possible difference in effect between primary and secondary Raynaud’s. Conclusions Chronic hand pain is a prevalent and serious condition and can cause significant morbidity and disability and interferes with independence and activities of daily living. Conservative treatment remains the first line of treatment; however, when first-line treatments fail, steroid injections can usually provide benefit. In some cases, HA or Botox may also be beneficial. US-guidance is increasing in hand injection and almost ubiquitously provides safer, more effective injections. Hand surgery remains the alternative for refractory pain.

This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory input. Genetic research has revealed familial aggregation of fibromyalgia and other related disorders like major depressive disorder. Dysfunctional pain processing may also be influenced by exposure to physical or psychological stressors, abnormal biologic reactions in the autonomic nervous system, and neuroendocrine responses. With more research the pathophysiology of fibromyalgia will be better understood, leading to more logical and focused treatment options for fibromyalgia patients.

Our objective is to present a brief history of the evolution of peripheral nerve stimulation, the current understanding of peripheral nerve stimulation mechanisms in chronic pain, peripheral nerve stimulation applications in upper extremity chronic pain conditions, and complications of peripheral nerve stimulation. The evolution of peripheral nerve stimulation from the early ages to the current status has been facilitated by discoveries in neurobehavioral mechanisms of pain, advances in technology and percutaneous lead development, and the availability of high-quality portable ultrasound units. Peripheral nerve stimulation application in managing upper extremity pain of amputated limbs, post-stroke shoulder pain, complex regional pain syndrome (CRPS), and median, ulnar, and radial neuropathies are discussed. Finally, we describe complications of peripheral nerve stimulation. The availability of ultrasound-guided peripheral nerve stimulation techniques and superior peripheral nerve stimulation technology have opened up new and minimally invasive treatment options for chronic intractable neuropathic pain of the upper extremity. Additionally, the ability to place peripheral nerve stimulation leads percutaneously without open peripheral nerve surgery expands the pool of implanting physicians, while simultaneously decreasing the risks and complications that are associated with open surgery.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

Peripheral nerve stimulation (PNS) is rapidly increasing in use. This interventional pain treatment modality involves modulating peripheral nerves for a variety of chronic pain conditions. This review evaluated its use specifically in the context of chronic lower extremity pain. Studies continue to elucidate the utility of PNS and better define indications, contraindications, as well as short- and long-term benefits of the procedure for the lower extremity. While large, prospective evidence is still lacking, the best available evidence suggests that improvements may be seen in pain scores, functionality, and opioid consumption. Overall, evidence synthesis suggests that PNS for the lower extremities may be a viable option for patients with chronic lower extremity pain.

Background. Spinal cord stimulation (SCS) has been used over decades for pain management, but migration of percutaneous leads has been the most common complication. Better surgical techniques and newer SCS technologies likely reduced the incidence of lead migration requiring surgical revision, although data are sparse. This study aimed to retrospectively evaluate the incidence of clinically significant percutaneous lead migration in patients permanently implanted with a 10 kHz SCS system. Methods. Consecutive patients with chronic trunk and/or limb pain, permanently implanted between January 2016 and June 2019, were included in the analysis. Data were collected from the hospital’s electronic medical records and the manufacturer’s database. Clinically significant lead migration, defined as diminished pain relief followed by surgery to correct lead location, was assessed at the 6-month follow-up. Results. At the 6-month follow-up, there were no cases of clinically significant lead migration, average pain relief was 65.2%, 82% of patients had response (≥50% pain relief), improvement of function was noted in 72% of patients, and decrease of medication was observed in 42% of patients. Therapy efficacy was sustained in patients with >12 months follow-up; the average pain relief was 58.5%, and the response rate was 82%. Conclusions. The surgical techniques in use today are designed to minimise the risk of percutaneous lead migration and may have reduced its incidence. In addition, new SCS systems may give greater opportunity to mitigate cases of minor lead movement using alternative stimulation programs.

With the significant rise in the prevalence of diabetes worldwide, diabetic peripheral neuropathy (DPN) remains the most common complication among type 1 and 2 diabetics. The adverse sequelae of DPN, which include neuropathic pain, diabetic foot ulcers and lower-limb amputations, significantly impact quality of life and are major contributors to the biopsychosocial and economic burden of diabetes at the individual, societal and health system levels. Because DPN is often diagnosed in the late stages of disease progression by electromyography (EMG), and neuropathic pain as a result of DPN is difficult to treat, the need for earlier detection is crucial to better ascertain and manage the condition. Among the various modalities available to aid in the early detection of DPN, functional magnetic resonance imaging (fMRI) has emerged as a practical tool in DPN imaging due to its noninvasive radiation-free nature and its ability to relate real-time functional changes reflecting the local oxygen consumption of regions of the CNS due to external stimuli. This review aims to summarize the current body of knowledge regarding the utility of fMRI in detecting DPN by observing central nervous system (CNS) activity changes among individuals with DPN when compared to controls. The evidence to date points toward a tendency for increased activity in various central neuroanatomical structures that can be detected by fMRI and positively correlates with diabetic neuropathic pain.

Electrical stimulation of peripheral nerves has been utilized for a variety of indications for over five decades [...]

Headaches are one of the most common medical complaints worldwide, and treatment is often made difficult because of misclassification. Peripheral nerve stimulation has emerged as a novel treatment for the treatment of intractable headaches in recent years. While high-quality evidence does exist regarding its use, efficacy is generally limited to specific nerves and headache types. While much research remains to bring this technology to the mainstream, clinicians are increasingly able to provide safe yet efficacious pain control.

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Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus that is associated with a significant decline in quality of life. Like other painful neuropathic conditions, PDN is difficult to manage clinically, and a variety of pharmacological and non-pharmacological options are available for this condition. Recommended pharmacotherapies include anticonvulsive agents, antidepressant drugs, and topical capsaicin; and tapentadol, which combines opioid agonism and norepinephrine reuptake inhibition, has also recently been approved for use. Additionally, several neuromodulation therapies have been successfully used for pain relief in PDN, including intrathecal therapy, transcutaneous electrical nerve stimulation (TENS), and spinal cord stimulation (SCS). Recently, 10 kHz SCS has been shown to provide clinically meaningful pain relief for patients refractory to conventional medical management, with a subset of patients demonstrating improvement in neurological function. This literature review is intended to discuss the dosage and prospective data associated with pain management therapies for PDN.

Background/Aim: Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection. Patients and Methods: Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. Results: Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST) level were 42 ± 7.7 years (range 20-56) and 68 ± 41.7 U/L (range 16-214), respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4) and 5.9 ± 15.2 (range 0.9-136.2), respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis. Conclusions: Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.

Continuous peripheral nerve blocks (CPNB) are commonly used for intraoperative and postoperative analgesia. Our study aimed at describing our experience with ambulatory peripheral nerve catheters. After Institutional Review Board approval, records for all patients discharged with supraclavicular or popliteal catheters between January 1, 2009 and December 31, 2011 were reviewed. A licensed practitioner provided verbal and written instructions to the patients prior to discharge. Daily follow-up phone calls were conducted. Patients either removed their catheters at home with real-time simultaneous telephone guidance by a member of the Acute Pain Service or had them removed by the surgeon during a regular office visit. The primary outcome of this analysis was the incidence of complications, categorized as pharmacologic, infectious, or other. The secondary outcome measure was the average daily pain score. Our study included a total of 1059 patients with ambulatory catheters (769 supraclavicular, 290 popliteal). The median infusion duration was 5 days for both groups. Forty-two possible complications were identified: 13 infectious, 23 pharmacologic, and 6 labeled as other. Two patients had retained catheters, 2 had catheter leakage, and 2 had shortness of breath. Our study showed that prolonged use of ambulatory catheters for a median period of 5 days did not lead to an increased incidence of complications.