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Conventionally, peripheral nerve stimulation (PNS) for treatment of chronic pain has involved a two-stage process: a short-term (e.g., 7 days) trial and, if significant pain relief is achieved, a permanent PNS system is implanted. A percutaneous PNS treatment is now available where a coiled lead may be implanted for up to 60 days with the goal of producing sustained relief. In the present review, published prospective trials using percutaneous PNS treatment were identified and synthesized. The collected evidence indicates that percutaneous PNS treatment for up to 60 days provides durable clinically significant improvements in pain and pain interference. Similar efficacy across diverse targets and etiologies supports the broad applicability for use within the chronic pain population using this nonopioid technology.

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). PAS can induce long‐term potentiation (LTP)‐like plasticity in humans, manifested as motor‐evoked potential (MEP) enhancement. We have developed a variant of PAS (“high‐PAS”), which consists of high‐frequency PNS and high‐intensity TMS and targets spinal plasticity and promotes rehabilitation after spinal cord injury (SCI). Vagus nerve stimulation (VNS) promotes LTP‐like plasticity and enhances recovery in SCI and stroke in humans and animals when combined with repetitive motor training. We combined high‐PAS with simultaneous noninvasive transcutaneous auricular VNS (aVNS) to determine if aVNS enhances the extent of PAS‐induced MEP amplitude increase. Sixteen healthy participants were stimulated for 20 min in four different sessions (PAS, PAS + aVNS, PAS + shamVNS, and aVNS) in a randomized single‐blind setup. MEPs were measured before, immediately after, and at 30, 60, and 90 min post‐stimulation. Stimulation protocols with PAS significantly potentiated MEPs (p = 0.005) when compared with aVNS (p = 0.642). Although not significant, MEP enhancement observed after PAS (43.5%) is further increased by aVNS (49.7%) and electrical earlobe stimulation (63.9%). Our aVNS setup failed to significantly enhance the effect of PAS, but sham VNS revealed a trend towards enhanced plasticity. Optimization of auricular VNS stimulation setup is required for possible tests of patients with SCI. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the performance of gradient array coils in minimizing switched‐gradient‐induced electric fields (E‐fields) and improving peripheral nerve stimulation (PNS) thresholds while generating gradient fields with adjustable linearity across customizable regions of linearity (ROLs). Methods: A body gradient array coil is used to reduce the induced E‐fields on the surface of a body model by modulating applied currents. This is achieved by performing an optimization problem with the peak E‐field as the objective function and current amplitudes as unknown variables. Coil dimensions and winding patterns are fixed throughout the optimization, whereas other engineering metrics remain adjustable. Various scenarios are explored by manipulating adjustable parameters. Results: The array design consistently yields lower E‐fields and higher PNS thresholds across all scenarios compared with a conventional coil. When the gradient array coil generates target gradient fields within a 44‐cm‐diameter spherical ROL, the maximum E‐field is reduced by 10%, 18%, and 61% for the X, Y, and Z gradients, respectively. Transitioning to a smaller ROL (24 cm) and relaxing the gradient linearity error results in further E‐field reductions. In oblique gradients, the array coil demonstrates the most substantial reduction of 40% in the Z–Y direction. Among the investigated scenarios, the most significant increase of 4.3‐fold is observed in the PNS thresholds. Conclusion: Our study demonstrated that gradient array coils offer a promising pathway toward achieving high‐performance gradient coils regarding gradient strength, slew rate, and PNS thresholds, especially in scenarios in which linear magnetic fields are required within specific target regions. [ABSTRACT FROM AUTHOR]

Introduction: We recently showed that sub-kilohertz electrical stimulation of the afferent somata in the dorsal root ganglia (DRG) reversibly blocks afferent transmission. Here, we further investigated whether similar conduction block can be achieved by stimulating the nerve trunk with electrical peripheral nerve stimulation (ePNS). Methods: We explored the mechanisms and parameters of conduction block by ePNS via ex vivo single-fiber recordings from two somatic (sciatic and saphenous) and one autonomic (vagal) nerves harvested from mice. Action potentials were evoked on one end of the nerve and recorded on the other end from teased nerve filaments, i.e., single-fiber recordings. ePNS was delivered in the middle of the nerve trunk using a glass suction electrode at frequencies of 5, 10, 50, 100, 500, and 1000 Hz. Results: Suprathreshold ePNS reversibly blocks axonal neural transmission of both thinly myelinated Aδ-fiber axons and unmyelinated C-fiber axons. ePNS leads to a progressive decrease in conduction velocity (CV) until transmission blockage, suggesting activity-dependent conduction slowing. The blocking efficiency is dependent on the axonal conduction velocity, with Aδ-fibers efficiently blocked by 50-1000 Hz stimulation and C-fibers blocked by 10-50 Hz. The corresponding NEURON simulation of action potential transmission indicates that the disrupted transmembrane sodium and potassium concentration gradients underly the transmission block by the ePNS. Discussion: The current study provides direct evidence of reversible Aδ- and C-fiber transmission blockage by low-frequency (<100 Hz) electrical stimulation of the nerve trunk, a previously overlooked mechanism that can be harnessed to enhance the therapeutic effect of ePNS in treating neurological disorders. [ABSTRACT FROM AUTHOR]

Purpose of Review: Recent research has shown the effectiveness of peripheral nerve stimulators (PNS) in managing chronic pain conditions. Ongoing studies aim to explore its potential application in treating acute postoperative pain states. The purpose of this systematic review is to assess the role of PNS in providing relief for postoperative pain. Recent Findings: Clinical studies investigating the use of peripheral nerve stimulators (PNS) for analgesia following various surgeries, such as total knee arthroplasty, anterior cruciate ligament repair, ankle arthroplasty, rotator cuff repair, hallux valgus correction, and extremity amputation, have shown promising results. Lead placement locations include the brachial plexus, sciatic, femoral, tibial, genicular, perineal, sural, radial, median, and ulnar nerves. These studies consistently report clinically significant reductions in pain scores, and some even indicate a decrease in opioid consumption following PNS for postoperative pain. Summary: PNS involves the subcutaneous placement of electrode leads to target peripheral nerve(s) followed by delivery of an electric current via an external pulse generator. While the precise mechanism is not fully understood, the theory posits that PNS modulates electrical stimulation, hindering the signaling of nociceptive pain. PNS presents itself as an alternative to opioid therapy, holding promise to address the opioid epidemic by offering a nonpharmacologic approach for both acute and chronic pain states. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted the immunomodulatory effects of acupuncture on sepsis and proposed novel non-pharmacological or bioelectronic approaches to managing inflammatory illnesses. Establishing rules for selectively activating sympathetic or vagal nerve-mediated anti-inflammatory pathways using acupuncture has valuable clinical applications. Over the years, studies have revealed the segmental modulatory role of acupuncture in regulating visceral function by targeting the autonomic nervous system (ANS). In this review, we aim to summarize recent findings on acupuncture in treating sepsis, focusing on the underlying ANS mechanism, as well as the rules of acupoint specificity, intensity, frequency, and other parameters utilized in these studies. Mechanistically, the immunomodulatory properties of the sympathetic nervous system have been highlighted. Furthermore, we explore the immunotherapeutic benefits of acupuncture in treating sepsis. A better understanding of the immunoregulatory mechanism of sympathetic nervous system may offer novel approaches for the development of therapeutics to treat or prevent a variety of inflammatory diseases. [ABSTRACT FROM AUTHOR]

John Hatheway,1 Alexander Perry Hersel,2 Jonathan Song,3 Mitchell P Engle,4 Genaro Gutierrez,5 Vishal Khemlani,6 Leonardo Kapural,7 Gregory Moore,8 Reginald Chinaedu Ajakwe,9 Drew M Trainor,10 Jennifer M Hah,11 Peter Staats,12 Paul Lynch,13 James Makous,14 Gary Heit15 ,† Shilpa Kottalgi,16 Mehul J Desai17 1Pain Management, Northwest Pain Care, Spokane, WA, USA; 2Pain Management, Pain Management and Injury Relief, Thousand Oaks, CA, USA; 3Pain Management, Arizona Pain Specialists, Scottsdale, AZ, USA; 4Pain Management, Institute of Precision Pain Medicine, Corpus Christi, TX, USA; 5Pain Management, Pain Specialists of America, Austin, TX, USA; 6Pain Management, Columbia Pain Management, Portland, OR, USA; 7Pain Management, Center for Clinical Research, Carolinas Pain Institute, Winston-Salem, NC, USA; 8Pain Management, Pacific Sports and Spine, Eugene, OR, USA; 9Pain Management, Comprehensive Spine & Pain, Burbank, CA, USA; 10Pain Management, Denver Spine and Pain Institute, Denver, CO, USA; 11Pain Management, Division of Pain Medicine, Stanford University, Palo Alto, CA, USA; 12Pain Management, Premier Pain Centers, Shrewsbury, NJ, USA; 13Pain Management, US Pain Care, Scottsdale, AZ, USA; 14Pain Management, Makous Research, LLC, Carlsbad, CA, USA; 15Department of Neurosurgery, Hue University of Medicine and Pharmacy, Hue, Vietnam; 16Clinical Affairs, Nalu Medical, Inc., Carlsbad, CA, USA; 17Pain Management, International Spine Pain & Performance Center, Washington, DC, USA†Gary Heit passed away in February 2023Correspondence: Shilpa Kottalgi, Nalu Medical, Inc., 2320 Faraday Ave, Carlsbad, CA, 92008, USA, Tel +1 858 344 1591, Fax +1 760 448 2379, Email skottalgi@nalumed.comBackground: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM).Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study.Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.Plain Language Summary: Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm3 in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (< 1.5 cm3 in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥ 50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months.Keywords: peripheral nerve stimulation, PNS, chronic pain, neuropathy, neuralgia, micro-IPG, battery-free

Mansoor M Aman,1 Yussr M Ibrahim,2 Merve Buluk Figueira,1 Ahish Chitneni,3 Ammar Mahmoud2 1Department of Anesthesiology, Division of Pain Medicine, Advocate Health, Oshkosh, WI, USA; 2Department of Anesthesiology, Division of Pain Medicine, Northern Light Eastern Maine Medical Center, Bangor, ME, USA; 3Department of Rehabilitation and Regenerative Medicine, New York-Presbyterian Hospital - Columbia and Cornell, New York, NY, USACorrespondence: Mansoor M Aman, Interventional Pain Medicine, Advocate Aurora Health, 700 N. Westhaven Drive, Oshkosh, WI, 54904, USA, Email mansoor.aman@aah.orgPurpose: This retrospective review evaluates pain and patient-defined functional goal improvement utilizing bipolar peripheral nerve stimulation (PNS) in chronic neuropathic and nociceptive pain states.Patients and Methods: Our dataset includes 24 patients who underwent implantation of a permanent peripheral nerve stimulator from January 2018 through December 2022. A total of 29 leads were implanted amongst 24 patients, with 5 patients having leads at 2 different dermatomes. Fifteen leads were placed for primarily neuropathic pain, and 14 leads were placed for nociceptive pain. Inclusion criteria were the following: pain duration greater than 6 months, documented peri-procedural Numerical Pain Rating Scale (NPRS) and greater than 60 days follow-up post implant.Results: Data was collected and analyzed showing that 89.6% of implants at 6 months follow-up and 70% at 12 months follow-up achieved 50% or greater pain relief. A significant reduction in NPRS scores when comparing pre-procedure pain scores (Median = 7, n = 29) to 6-month follow-up data (Median = 2, n = 29), p< 0.001 with a large effect size, r = 0.61. Ninety-three percent of patients reported achieving their personal functional goal. Twelve of the fourteen (86%) leads implanted for primary nociceptive pain and fourteen of the fifteen (93%) leads implanted for neuropathic pain achieved ≥ 50% relief at 6 months. At twelve months, seven leads in each group provided ≥ 50% sustained pain relief. Of the 14 patients that were on opioids, 6 discontinued, while another 2 had a reduction in oral morphine milligram equivalents (MME) at the 12-month follow-up.Conclusion: This retrospective review demonstrates the potential clinical application of PNS in both nociceptive and neuropathic pain states. Further prospective studies are warranted to validate the effectiveness of PNS in the treatment of refractory nociceptive and neuropathic pain states.Keywords: peripheral nerve stimulation, neuromodulation, neuropathic pain, nociceptive pain, chronic pain

There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham −2.17; mean difference (MD) = −4.42; 95 % confidence interval [CI] −1.57 to −7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = −4.50; p = 0.02) and medication-naïve (MD = −4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = −4.30; 95 % CI -1.36 to −7.24; p = 0.004). The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants. • Tonic motor activation (TOMAC) reduces restless legs syndrome (RLS) symptoms. • TOMAC is efficacious for both medication-refractory and -naïve RLS patients. • TOMAC is safe and well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: Peripheral nerve stimulation (PNS) limits the usability of state‐of‐the‐art whole‐body and head‐only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole‐body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. Methods: We designed, constructed, and tested two actively shielded whole‐body Y‐axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS‐optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head‐imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). Results: The PNS‐optimized design YG2 achieved 46% higher average experimental thresholds for a head‐imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (−3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. Conclusion: The PNS‐optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans. [ABSTRACT FROM AUTHOR]

Leonardo Kapural,1 Jim Melton,2 Billy Kim,3 Priyesh Mehta,4 Abindra Sigdel,5 Alexander Bautista,6 Erika A Petersen,7 Konstantin V Slavin,8,9 John Eidt,10 Jiang Wu,11 Said Elshihabi,12 Jason Matthew Schwalb,13 H Edward Garrett Jr,14 Elias Veizi,15 Giancarlo Barolat,16 Ravi R Rajani,17 Peter C Rhee,18 Maged Guirguis,19 Nagy Mekhail20 1Carolinas Pain Institute and Center for Clinical Research, Winston-Salem, NC, USA; 2Department of Vascular Surgery, Cardiovascular Health Clinic, Oklahoma City, OK, USA; 3Department of Vascular Surgery, The Surgical Clinic, Nashville, TN, USA; 4Department of Pain Medicine, Meta Medical Research Institute, Dayton, OH, USA; 5Department of Surgery, University of Louisville, Louisville, KY, USA; 6Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA; 7Department of Neurosurgery, University of Arkansas, Little Rock, AR, USA; 8Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA; 9Department of Neurology, Jesse Brown VA Medical Center, Chicago, IL, USA; 10Department of Vascular Surgery, Baylor Scott and White Heart and Vascular Hospital Dallas, Dallas, TX, USA; 11Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA, USA; 12Department of Neurosurgery, Legacy Brain & Spine Surgical Center, Atlanta, GA, USA; 13Department of Neurosurgery, Henry Ford Medical Group, Detroit, MI, USA; 14Department of Vascular Surgery, University of Tennessee-Memphis, Memphis, TN, USA; 15Department of Pain Medicine, VA Northeast OH Healthcare System, Cleveland, OH, USA; 16Department of Neurosurgery, Barolat Neuroscience, Presbyterian/St Luke’s Medical Center, Denver, CO, USA; 17Department of Vascular Surgery, Emory University and Grady Memorial Hospital, Atlanta, GA, USA; 18Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 19Department of Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 20Department of Pain Management, Cleveland Clinic, Cleveland, OH, USACorrespondence: Leonardo Kapural, Carolinas Pain Institute and Center for Clinical Research, 145 Kimel Park Dr &num;330, Winston-Salem, NC, 27103, USA, Email lkapuralmd@gmail.comPurpose: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain.Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥ 50% pain relief 30 min after treatment in ≥ 50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined.Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups.Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.Keywords: post-amputation pain, phantom limb pain, neuromodulation, peripheral nerve stimulation, high-frequency nerve block

Sailesh Arulkumar,1 Elisa E Neuchat,2 Eric Ly,3 Austin Ingwei Ly,4 Kiana Fahimipour,5 Mehul J Desai6,7 1Department of Anesthesiology, SSM Health, St. Anthony’s Hospital, Oklahoma City, OK, USA; 2School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA; 3Department of Anesthesiology, Brown University, Rhode Island Hospital, Providence, RI, USA; 4The University of Tennessee Health Science Center College of Medicine, Memphis, TN, USA; 5Department of Anesthesiology; Louisiana State University Health Sciences Center at New Orleans, New Orleans, LA, USA; 6International Spine Pain & Performance Center, Washington, DC, USA; 7George Washington University School of Medicine and Health Sciences, Washington, DC, USACorrespondence: Mehul J Desai, International Spine Pain and Performance Center, 2021 K Street NW Suite 615, Washington, DC, 20006, USA, Tel +1.202.808.8295, Fax +1.202.808.8296, Email drdesai@isppcenter.comAbstract: Scapulalgia or shoulder pain accounts for 16% of all musculoskeletal complaints in the healthy adult population and becomes more common as we age. When this pain exceeds 3 months in duration, it is deemed to be chronic, and typically treated in an escalating manner. Spanning a continuum of conservative and non-conservative measures, chronic shoulder pain treatments range from rest and physical therapy to surgery. Since each patient presents with a unique spectrum of symptoms a customized treatment plan is often required. Over the lifetime of many of these patients, a variety of treatment options are required. One of these treatment options, peripheral nerve stimulation (PNS), is a minimally invasive procedure in which an electrical impulse is delivered through a percutaneously implanted, small caliber electrode to a peripheral nerve proximal to the lesion which interferes with the pain signals. Over the past several years, significant growth of PNS in the treatment of chronic neuropathic pain has been observed. However, the procedural techniques have not been well described. The foundation of long-term, minimally invasive percutaneous PNS in patients with chronic shoulder pain, and procedural techniques for stimulating the suprascapular and axillary nerves using fluoroscopy or ultrasonography will be described in this report.Keywords: scapulalgia, shoulder pain, chronic pain, suprascapular nerve, axillary nerve, peripheral nerve stimulation

Purpose of Review: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. Recent Findings: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. Summary: PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain. [ABSTRACT FROM AUTHOR]

Spinal cord injuries (SCI) often result in motor impairment and lifelong disability. This systematic review, conducted in agreement with PRISMA guidelines, aimed to evaluate the effects of cortico-spinal paired associative stimulation (PAS) on motor outcomes in individuals with SCI. PubMed, Scopus/EMBASE, Pedro, and Cochrane databases were consulted from inception to 2023/01/12. In 1021 articles, 10 studies involving 84 patients meet the inclusion criteria, 7 case series/study, and 3 clinical trials. Despite light differences, the included studies performed a cortico-peripheral PAS using a single transcranial magnetic stimulation and high frequency electrical peripheral nerve stimulation for a consistent number of sessions (>20). All included studies reported improvement in motor outcomes recorded via clinical and/or neurophysiological assessment. Available evidence showed an increase in motor outcomes after PAS stimulation. Indeed, both clinical and neurophysiological outcomes suggest the effectiveness of a high number of PAS sessions in chronic individuals with SCI. Due to a limited number of studies and an unsatisfactory study design, well-designed RCTs are needed to confirm the potentiality of these approaches and clarify the adequate dose-response of PAS in the SCI population. The protocol was registered on the PROSPERO database (CRD42023485703). [ABSTRACT FROM AUTHOR]

Chronic pain, a complex and debilitating condition, poses a significant challenge to both patients and healthcare providers worldwide. Conventional pharmacological interventions often prove inadequate in delivering satisfactory relief while carrying the risks of addiction and adverse reactions. In recent years, electric neuromodulation emerged as a promising alternative in chronic pain management. This method entails the precise administration of electrical stimulation to specific nerves or regions within the central nervous system to regulate pain signals. Through mechanisms that include the alteration of neural activity and the release of endogenous pain-relieving substances, electric neuromodulation can effectively alleviate pain and improve patients' quality of life. Several modalities of electric neuromodulation, with a different grade of invasiveness, provide tailored strategies to tackle various forms and origins of chronic pain. Through an exploration of the anatomical and physiological pathways of chronic pain, encompassing neurotransmitter involvement, this narrative review offers insights into electrical therapies' mechanisms of action, clinical utility, and future perspectives in chronic pain management. [ABSTRACT FROM AUTHOR]

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short‐latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise‐induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing–remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3‐min 15% MVC, immediately followed by a low‐intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p <.001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between‐group differences in SSEPs, MS‐related SAI differences during the fatiguing contractions were most likely associated with disease‐related changes in central integration. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries often result in severe personal and social burden, and even with surgical treatment, patients continue to have poor clinical outcomes. Over the past two decades, electrical stimulation has been shown to promote axonal regeneration and alleviate refractory neuropathic pain. The aim of this study was to analyse this field using a bibliometric approach. Literature was searched through Web of Science Core Collection (WOSCC) for the years 2002–2023. Literature analysis included: (1) Describing publication trends in the field. (2) Exploring collaborative network relationships. (3) Finding research advances and research hotspots in the field. (4) Summarizing research trends in the field. With the number of studies in this field still increasing, a total of 693 publications were included in the analysis. This field of research is interdisciplinary in nature. Research hotspots include peripheral nerve regeneration, the treatment of neuropathic pain, materials for nerve injury repair, and the restoration of sensory function in patients with peripheral nerve injury. Correspondingly, the development of nerve conduits and systems for peripheral nerve electrical stimulation, clinical trials of peripheral nerve electrical stimulation, and tactile recovery and movement for amputees have shown significant promise as future research trends in this field. [ABSTRACT FROM AUTHOR]

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE) on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) in individuals with supraspinatus tendinopathy. Participants (n = 50) were divided into two groups; they received 4 treatment sessions, 1 per week, of PE and PNS (n = 25) or 10 treatment sessions of TENS and US (n = 25). Both groups performed the EE program consisting of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p < 0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment with PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied. [ABSTRACT FROM AUTHOR]

Acupuncture is increasingly used to manage high blood pressure (BP) as a complementary therapy. However, the mechanisms underlying its hypotensive effects remain unclear. Our previous studies have shown that electroacupuncture (EA) at the ST36-37 acupoints, overlying the deep peroneal nerve, attenuates pressor responses through adenosine A2A receptors (A2AR) in the rostral ventrolateral medulla (rVLM). However, it is uncertain whether rVLM A2AR contributes to EAs BP-lowering effect in sustained hypertension. We hypothesized that a course of EA treatment lowers BP, in part, through the activation of adenosine A2AR in the rVLM in hypertensive rats. To mimic essential hypertension in the clinic, we performed EA in conscious Dahl salt-sensitive hypertensive rats (DSHRs). EA (0.1-0.4 mA, 2 Hz) was applied at ST36-37 for 30 min twice weekly for four weeks, while sham-EA was conducted in a similar manner but without electrical input. In hypertensive rats, BP was reduced by EA (n = 14) but neither by sham-EA (n = 14) nor in the absence of needling (n = 8). Following four weeks of eight treatments and then under anesthesia, EAs modulatory effect on elevated BP was reversed by unilateral rVLM microinjection of SCH 58261 (1 mM in 50 nl; an A2AR antagonist; n = 7; P

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Abstract Background The prevalence of sacroiliac joint pain (SIJP) is estimated to be 10–30% in patients with chronic low back pain. Numerous conservative and surgical treatment modalities for SIJP have been described with limited evidence regarding long-term pain relief. Spinal cord stimulation (SCS) is a well-established technique to treat patients with chronic low back pain. However, the effect on patients with SIJP is not consistent. Therefore, peripheral nerve stimulation (PNS) for chronic SIJP was implemented in experimental trials. Clinical data on PNS for SIJP is still lacking. The authors present a case series and a protocol for a prospective, multicenter study to determine the effect of PNS in patients with chronic intractable SIJP. Method A multicenter, prospective randomized controlled trial was designed. Patients with chronic intractable SIJP will be recruited and randomized in a 4:3 ratio to either the peripheral nerve stimulation group or to the best medical treatment group. A total of 90 patients are planned to be enrolled (52 in the PNS group and 38 in the BMT group). Patients in the intervention group receive a percutaneous implantation of a unilateral or bilateral lead which is externalized for a trial phase for 3–14 days. After trial phase only patients with at least 50% reduction of pain receive an impulse generator for permanent stimulation. Regular visits for participants are planned on day 0, after 3 months (± 30 days), 6 months (± 30 days), and 12 months (± 60 days). The primary outcome measurements is the difference in Numeric Pain Rating Scale (NRS) between baseline and after 6 months. Secondary outcomes is improvement of pain associated disability (ODI) and improvement of health-related quality of life after 6 and 12 months. Discussion We have described the protocol for a prospective, multicenter, randomized trial evaluating the influence of PNS on patients with chronic sacroiliac joint syndrome. We believe that PNS on patients with chronic sacroiliac joint syndrome will show promising results regarding pain relief and quality of life in comparison to BMT after 12 months. The design of this trial promises high evidence in comparison to the data to date. Trial registration ClinicalTrials.gov, NCT05357300. Registered on April 26, 2022.

Nerve stimulation is a rapidly developing field, demonstrating positive outcomes across several conditions. Despite potential benefits, current nerve stimulation devices are large, complicated, and are powered via implanted pulse generators. These factors necessitate invasive surgical implantation and limit potential applications. Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications. However, device miniaturization presents a serious engineering challenge. This review presents significant advancements from several groups that have overcome this challenge and developed millimetric-sized nerve stimulation devices. These are based on antennas, mini-coils, magneto-electric and opto-electronic materials, or receive ultrasound power. We highlight key design elements, findings from pilot studies, and present several considerations for future applications of these devices.

Pawe&lstrok; Radkowski,1– 3 Agnieszka Bara&nacute;ska,1 Marcin Mieszkowski,1,2 Justyna Dawidowska-Fidrych,4 Katarzyna Podhorodecka1 1Department of Anaesthesiology and Intensive Care, Regional Specialist Teaching Hospital, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland; 3Department of Anaesthesiology and Intensive Care, Hospital zum heiligen Geist, Fritzlar, Germany; 4Pediatric Department, Hospital Pro-Medica, E&lstrok;k, PolandCorrespondence: Katarzyna Podhorodecka, Email k.podhorodecka1@gmail.comAbstract: The administration of general anesthesia is a crucial aspect of surgery. However, it can pose significant risks to patients, such as respiratory depression and prolonged neuromuscular blockade. To avoid such complications, it is essential to monitor neuromuscular transmission during anesthesia. While clinical tests have been used for decades to evaluate muscle function, they are now known to be unreliable, and relying on them increases the risk of postoperative complications. Thankfully, there are now six methods available for neuromuscular monitoring during anesthesia: mechanomyography, acceleromyography, electromyography, kinemyography, phonomyography, and compressomyography. Each of these methods differs in terms of their approach and methodology, and their importance in clinical practice varies accordingly. Mechanomyography involves measuring the mechanical response of a muscle to nerve stimulation, while acceleromyography measures the acceleration of muscle contraction. Electromyography records the electrical activity of muscles, while kinemyography tracks muscle movement. Phonomyography records the sound waves produced by contracting muscles, and compressomyography involves monitoring the pressure changes in a muscle during contraction. Overall, understanding the differences between these methods and their clinical significance is crucial for anesthesiologists. This review aims to provide an updated understanding of the current methods available for neuromuscular monitoring during anesthesia, so that anesthesiologists can make informed decisions about patient care and reduce the risk of postoperative complications.Keywords: neuromuscular monitoring, neuromuscular blockade, peripheral nerve stimulation, anesthesiology, review

Background: The prevalence of sacroiliac joint pain (SIJP) is estimated to be 10–30% in patients with chronic low back pain. Numerous conservative and surgical treatment modalities for SIJP have been described with limited evidence regarding long-term pain relief. Spinal cord stimulation (SCS) is a well-established technique to treat patients with chronic low back pain. However, the effect on patients with SIJP is not consistent. Therefore, peripheral nerve stimulation (PNS) for chronic SIJP was implemented in experimental trials. Clinical data on PNS for SIJP is still lacking. The authors present a case series and a protocol for a prospective, multicenter study to determine the effect of PNS in patients with chronic intractable SIJP. Method: A multicenter, prospective randomized controlled trial was designed. Patients with chronic intractable SIJP will be recruited and randomized in a 4:3 ratio to either the peripheral nerve stimulation group or to the best medical treatment group. A total of 90 patients are planned to be enrolled (52 in the PNS group and 38 in the BMT group). Patients in the intervention group receive a percutaneous implantation of a unilateral or bilateral lead which is externalized for a trial phase for 3–14 days. After trial phase only patients with at least 50% reduction of pain receive an impulse generator for permanent stimulation. Regular visits for participants are planned on day 0, after 3 months (± 30 days), 6 months (± 30 days), and 12 months (± 60 days). The primary outcome measurements is the difference in Numeric Pain Rating Scale (NRS) between baseline and after 6 months. Secondary outcomes is improvement of pain associated disability (ODI) and improvement of health-related quality of life after 6 and 12 months. Discussion: We have described the protocol for a prospective, multicenter, randomized trial evaluating the influence of PNS on patients with chronic sacroiliac joint syndrome. We believe that PNS on patients with chronic sacroiliac joint syndrome will show promising results regarding pain relief and quality of life in comparison to BMT after 12 months. The design of this trial promises high evidence in comparison to the data to date. Trial registration: ClinicalTrials.gov, NCT05357300. Registered on April 26, 2022. [ABSTRACT FROM AUTHOR]

Introduction: Sensorimotor integration is important, if not required, when using our hands. The integration of the tactile and motor systems is disrupted in individuals with upper limb amputations because their connection to their fingertips is lost. Direct cortical stimulation allows for modality and location matched perceptions; however, studies show that the time to process and act upon direct cortical feedback significantly exceeds the time to do the same with naturally produced tactile feedback. Direct cortical stimulation does not engage multiple parallel structures in the brain stem meant to integrate tactile feedback with signals from the motor system at a sub-perceptual or pre-perceptual level before the somatosensory cortex is involved. While reasonable to assume, it is not known if the artificially generated signals will engage the same peripheral tactile pathways to the pre-perceptual and perceptual structures as natural tactile sensation. Our hypothesis is that pre-perceptual structures will process the electrically generated neural activity as it would naturally generated neural activity. Methods: In this study, stimulation of the median nerve in multiple subjects' residual limbs produced modal, and location matched sensory perceptions in their hands. We found the time to process different stimuli using simple reaction time tests in three different formats. Results: We showed the minimum time to process peripheral nerve stimulation and initiate a motor plan is similar to naturally generated tactile feedback and is processed upwards of 50 - 175 ms faster than visual feedback alone. We also found the effect of stimulation intensity on the rate of feedback processing follows the same trend of natural sensory feedback, Piéron's law indicating that the unimodal processing of PNS is similar to natural touch. Finally, we found that tactile feedback given to a pre-perceptual level is again used in the motor plan. Discussion: Taken together, we conclude that peripheral nerve stimulation engages the pre-perceptual pathways of the brain, and hence demonstrate advantages of peripheral restoration of sensory inputs. [ABSTRACT FROM AUTHOR]

Postherpetic neuralgia (PHN) is a debilitating complication of varicella-zoster virus infection. This case report presents a novel approach to treating refractory trigeminal maxillary postherpetic neuralgia using digital subtraction angiography (DSA)-guided peripheral nerve stimulation via the foramen rotundum. A 72-year-old female with severe, treatment-resistant pain underwent this intervention. The results demonstrated the disappearance of tactile allodynia, a significant reduction in oral analgesic requirements, and no observed complications or side effects during a 3-year follow-up period. This case highlights the potential effectiveness of DSA-guided peripheral nerve stimulation using a new dorsal root ganglion (DRG) stimulator as an alternative therapy for refractory trigeminal postherpetic neuralgia (TPHN). [ABSTRACT FROM AUTHOR]

The enigmatic benefits of acute limb ischemic preconditioning (IP) in enhancing muscle force and exercise performance have intrigued researchers. This study sought to unravel the underlying mechanisms, focusing on increased neural drive and the role of spinal excitability while excluding peripheral factors. Soleus Hoffmann (H)‐reflex /M‐wave recruitment curves and unpotentiated supramaximal responses were recorded before and after IP or a low‐pressure control intervention. Subsequently, the twitch interpolation technique was applied during maximal voluntary contractions to assess conventional parameters of neural output. Following IP, there was an increase in both maximum normalized force and voluntary activation (VA) for the plantar flexor group, with negligible peripheral alterations. Greater benefits were observed in participants with lower VA levels. Despite greater H‐reflex gains, soleus volitional (V)‐wave and sEMG amplitudes remained unchanged. In conclusion, IP improves muscle force via enhanced neural drive to the muscles. This effect appears associated, at least in part, to reduced presynaptic inhibition and/or increased motoneuron excitability. Furthermore, the magnitude of the benefit is inversely proportional to the skeletal muscle's functional reserve, making it particularly noticeable in under‐recruited muscles. These findings have implications for the strategic application of the IP procedure across diverse populations. [ABSTRACT FROM AUTHOR]

Background: Chronic pelvic pain is a burdensome condition that involves multiple medical sub‐specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large‐scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. Materials and Methods: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. Results: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. Conclusions: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short‐term benefit, but long‐term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful. [ABSTRACT FROM AUTHOR]

Peripheral nerve stimulators have emerged as a crucial instrument in the realm of neurological disease, capable of modulating nerve activity through precisely targeted electrical stimulation to specific sites within the nervous system. Herein, a new wireless battery‐free peripheral nerve stimulation device for remote muscle activation is developed. The device with conch‐inspired bionic design can be wirelessly powered and controlled by a mobile phone playing audio via the piezoelectric effect. The device consists of two parts: a conch‐like signal‐intensifying piezoelectric resonator for converting acoustic wave into electrostimulation signal; and a pedestal with stimulation electrodes for transmitting the electrostimulation signal to a peripheral nerve. For remote nerve intervention, a programmed audio tone from one mobile phone can be tele‐transmitted from other phones according to the desired stimulation protocols. In‐vivo experiments in stimulating the sciatic nerve in mice showed that the device can activate muscles (e.g., 1 Hz 920 mV for 26 degree of leg movement), and the neuron‐muscle interaction has been confirmed by electromyogram (EMG). The wireless peripheral nerve stimulation conch achieves feasible remote muscle activation without batteries, and can extend the scope of self‐powered techniques for telemedicine and limb/trunk rehabilitation. [ABSTRACT FROM AUTHOR]

The article focuses on the use of peripheral nerve stimulation (PNS) for pain relief and dermatological changes in patients with complex regional pain syndrome (CRPS). Topics discussed include the clinical presentation of CRPS, the challenges in its management, and the therapeutic efficacy of PNS in addressing both pain and associated dermatological symptoms.

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Abstract Background There is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS. Methods This prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2–3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5. Results On average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity. Conclusions For refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS. Trial registration ClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.

Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channel–mediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].

Effective pain control of herpes zoster ophthalmicus (HZO) is not only essential to attenuate the clinical symptoms but to reduce the risk of postherpetic neuralgia development. Recently, neuromodulation therapy has been one promising option for neuropathic pain and increasingly applied in management of zoster-related pain. One key factor of neuromodulation treatment is the therapeutic site for the impaired nerves. In this study we aim to investigate one novel dual-neuromodulation strategy, targeting the level of the peripheral branch and trigeminal ganglion, in the pain management of HZO. Dual neuromodulation strategy combining short-term peripheral nerve stimulation (PNS) with pulsed radiofrequency (PRF) of trigeminal ganglion was compared with single PNS treatment for HZO-related pain. Clinical recordings of patients were retrospectively reviewed. The primary outcome was the pain severity, assessed by the visual analogue scale (VAS) before and after neuromodulation therapy. PNS achieved significant relief of pain with or without PRF treatment before discharge, which provided enduring therapeutic effect up to 12-month follow-up. The mean reduction of VAS was 6.7 ± 1.4 in dual modulation therapy (n = 13) at last follow-up and 5.4 ± 1.5 in PNS subgroup (n = 20), respectively. Moreover, dual modulation strategy provided better control of pain compared with PNS therapy alone at each time point. It is feasible and effective to combine the PNS and PRF in pain management of HZO. This novel dual modulation strategy of trigeminal pathway may provide additional therapeutic effects of pain symptoms in HZO population. Dual neuromodulation strategy for pain management of herpes zoster ophthalmicus is proposed, with regard to stimulation site (peripheral and trigeminal ganglion) and apparatus (electrical nerve stimulation and pulsed radiofrequency). Superior clinical outcome was associated with novel neuromodulation therapy with dual therapeutic targets, when compared with peripheral nerve stimulation in treatment of herpes zoster ophthalmicus. We conducted literature review to compare distinct pattern of neuromodulation (peripheral nerve stimulation and radiofrequency) in treatment of trigeminal neuropathic pain caused by herpes zoster. [ABSTRACT FROM AUTHOR]

Objective Chronic low back pain (CLBP) is multifactorial in nature, with recent research highlighting the role of multifidus dysfunction in a subset of nonspecific CLBP. This review aimed to provide a foundational reference that elucidates the pathophysiological cascade of multifidus dysfunction, how it contrasts with other CLBP etiologies and the role of restorative neurostimulation. Methods A scoping review of the literature. Results In total, 194 articles were included, and findings were presented to highlight emerging principles related to multifidus dysfunction and restorative neurostimulation. Multifidus dysfunction is diagnosed by a history of mechanical, axial, nociceptive CLBP and exam demonstrating functional lumbar instability, which differs from other structural etiologies. Diagnostic images may be used to grade multifidus atrophy and assess other structural pathologies. While various treatments exist for CLBP, restorative neurostimulation distinguishes itself from traditional neurostimulation in a way that treats a different etiology, targets a different anatomical site, and has a distinctive mechanism of action. Conclusions Multifidus dysfunction has been proposed to result from loss of neuromuscular control, which may manifest clinically as muscle inhibition resulting in altered movement patterns. Over time, this cycle may result in potential atrophy, degeneration and CLBP. Restorative neurostimulation, a novel implantable neurostimulator system, stimulates the efferent lumbar medial branch nerve to elicit repetitive multifidus contractions. This intervention aims to interrupt the cycle of dysfunction and normalize multifidus activity incrementally, potentially restoring neuromuscular control. Restorative neurostimulation has been shown to reduce pain and disability in CLBP, improve quality of life and reduce health care expenditures. [ABSTRACT FROM AUTHOR]

The study evaluated the reliability and repeatability of the force and surface electromyography activity (EMG) outcomes obtained through voluntary and electrically evoked contractions of knee extensors in females (n = 18) and males (n = 20) and compared these data between sexes. Maximal isometric voluntary contractions (iMVCs) of knee extensors associated with electrical stimulation of the femoral nerve were performed over 4 days (48-h interval), with the first day involving familiarization procedures, the second involving three trials (1-h interval), and the third and fourth involving just one trial. The intraclass correlation coefficient (ICC), coefficient of variation (CV), and repeatability of outcomes from within- and betweenday trials were determined for each sex. Females presented lower maximal voluntary force during iMVC (iMVCForce) and associated vastus lateralis EMG activity (root mean square, RMSVL), force evoked by potentiated doublet high-frequency (Db100Force) and single stimuli (Qtw), and M-wave amplitude than males (P - 0.01, partial eta squared -0.94). Voluntary activation (VA) and RMSVL/M-wave amplitude did not differ between sexes. iMVCForce, VA, Db100Force, Qtw, and M-wave amplitude were the most reliable outcomes in within-day trials, with similar results between sexes (ICC > 0.62; CV < 6.4%; repeatability: 12.2%-22.6%). When investigating between-day trials, the iMVCForce, VA, Db100Force, and Qtw were the most reliable (ICC > 0.66; CV < 7.5%; repeatability: 13.2%-33.45%) with similar results between sexes. In conclusion, females presented lower iMVCForce and evoked response than males. Although reliability and repeatability statistics vary between trials, data (e.g., from EMG or force signal), and sexes, most of the outcomes obtained through this technique are reliable in females and males. [ABSTRACT FROM AUTHOR]

Background: There is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS. Methods: This prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2–3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5. Results: On average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity. Conclusions: For refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS. Trial registration: ClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021. [ABSTRACT FROM AUTHOR]

Purpose of Review: Neurostimulation treatment options have become more commonly used for chronic pain conditions refractory to these options. In this review, we characterize current neurostimulation therapies for chronic pain conditions and provide an analysis of their effectiveness and clinical adoption. This manuscript will inform clinicians of treatment options for chronic pain. Recent Findings: Non-invasive neurostimulation includes transcranial direct current stimulation and repetitive transcranial magnetic stimulation, while more invasive options include spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), dorsal root ganglion stimulation, motor cortex stimulation, and deep brain stimulation. Developments in transcranial direct current stimulation, repetitive transcranial magnetic stimulation, spinal cord stimulation, and peripheral nerve stimulation render these modalities most promising for the alleviating chronic pain. Summary: Neurostimulation for chronic pain involves non-invasive and invasive modalities with varying efficacy. Well-designed randomized controlled trials are required to delineate the outcomes of neurostimulatory modalities more precisely. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. Methods: This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180 days, and 1, 2 and 3 years after the activation visit. Results: Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3 years. After 3 years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. Conclusions: The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. Trial Registration: ClinicalTrials.gov Identifier: NCT01985230. [ABSTRACT FROM AUTHOR]

Although there are many biochemical methods to measure amyloid-β (Aβ)42 concentration, one of the critical issues in the study of the effects of Aβ42 on the nervous system is a simple physiological measurement. The in vitro rat sciatic nerve model is employed and the nerve action potential (NAP) is quantified with different stimuli while exposed to different concentrations of Aβ42. Aβ42 predominantly reduces the NAP amplitude with minimal effects on other parameters except at low stimulus currents and short inter-stimulus intervals. The effects of Aβ42 are significantly concentration-dependent, with a maximum reduction in NAP amplitude at a concentration of 70 nM and smaller effects on the NAP amplitude at higher and lower concentrations. However, even physiologic concentrations in the range of 70 pM did reduce the NAP amplitude. The effects of Aβ42 became maximal 5–8 h after exposure and did not reverse during a 30 min washout period. The in vitro rat sciatic nerve model is sensitive to the effects of physiologic concentrations of Aβ42. These experiments suggest that the effect of Aβ42 is a very complex function of concentration that may be the result of amyloid-related changes in membrane properties or sodium channels. [ABSTRACT FROM AUTHOR]

Purpose of Review: Though peripheral nerve stimulation has long been utilized in the field of chronic pain management, its use in acute pain management in the postoperative period is relatively novel and warrants further consideration. Recent Findings: In the postsurgical period, peripheral nerve stimulation may offer an additional low-risk, opioid-sparing analgesic option, which is particularly pertinent in the setting of the ongoing opioid epidemic, as inadequate postsurgical analgesia has been shown to increase the risk of developing persistent or chronic postsurgical pain. Summary: In this review, we discuss the current literature that illustrate the emerging role of peripheral nerve stimulation as an effective treatment modality in the postoperative period for the management of acute pain, as various studies have recently been conducted evaluating the feasibility of utilizing percutaneous peripheral nerve stimulation as an adjunct in postsurgical analgesia. Nonetheless, future studies are necessary to continue to elucidate the short- and long-term impacts of peripheral nerve stimulation use in acute postsurgical analgesia. [ABSTRACT FROM AUTHOR]

IntroductionSensorimotor integration is important, if not required, when using our hands. The integration of the tactile and motor systems is disrupted in individuals with upper limb amputations because their connection to their fingertips is lost. Direct cortical stimulation allows for modality and location matched perceptions; however, studies show that the time to process and act upon direct cortical feedback significantly exceeds the time to do the same with naturally produced tactile feedback. Direct cortical stimulation does not engage multiple parallel structures in the brain stem meant to integrate tactile feedback with signals from the motor system at a sub-perceptual or pre-perceptual level before the somatosensory cortex is involved. While reasonable to assume, it is not known if the artificially generated signals will engage the same peripheral tactile pathways to the pre-perceptual and perceptual structures as natural tactile sensation. Our hypothesis is that pre-perceptual structures will process the electrically generated neural activity as it would naturally generated neural activity.MethodsIn this study, stimulation of the median nerve in multiple subjects’ residual limbs produced modal, and location matched sensory perceptions in their hands. We found the time to process different stimuli using simple reaction time tests in three different formats.ResultsWe showed the minimum time to process peripheral nerve stimulation and initiate a motor plan is similar to naturally generated tactile feedback and is processed upwards of 50 – 175 ms faster than visual feedback alone. We also found the effect of stimulation intensity on the rate of feedback processing follows the same trend of natural sensory feedback, Piéron’s law indicating that the unimodal processing of PNS is similar to natural touch. Finally, we found that tactile feedback given to a pre-perceptual level is again used in the motor plan.DiscussionTaken together, we conclude that peripheral nerve stimulation engages the pre-perceptual pathways of the brain, and hence demonstrate advantages of peripheral restoration of sensory inputs.