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Implantable neuromodulation devices typically have metal in contact with soft, ion-conducting nerves. These neural interfaces excite neurons using short-duration electrical pulses. While this approach has been extremely successful for multiple clinical applications, it is limited in delivering long-duration pulses or direct current (DC), even for acute term studies. When the charge injection capacity of electrodes is exceeded, irreversible electrochemical processes occur, and toxic byproducts are discharged directly onto the nerve, causing biological damage. Hydrogel coatings on electrodes improve the overall charge injection limit and provide a mechanically pliable interface. To further extend this idea, we developed a silicone-based nerve cuff lead with a hydrogel microfluidic conduit. It serves as a thin, soft and flexible interconnection and provides a greater spatial separation between metal electrodes and the target nerve. In an in vivo rat model, we used this cuff to stimulate and record from sciatic nerves, with performance comparable to that of metal electrodes. Further, we delivered DC through the lead in an acute manner to induce nerve block that is reversible. In contrast to most metallic cuff electrodes, which need microfabrication equipment, we built this cuff using a consumer-grade digital cutter and a simplified molding process. Overall, the device will be beneficial to neuromodulation researchers as a general-purpose nerve cuff electrode for peripheral neuromodulation experiments.

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.

Ron Dabby,1,2 Menachem Sadeh,1,2 Ilan Goldberg,1,2 Vitaly Finkelshtein1,2 1Department of Neurology, Wolfson Medical Center, Holon, 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Peripheral neuropathic pain (PNP) is caused by neuronal damage to the peripheral nervous system and usually affects the distal extremities. This open-label study examined the effect of short-term peripheral nerve stimulation (PNS) on individuals with PNP due to polyneuropathy. A total of 12 patients (mean age, 63.0 ± 10.0 years, 41.7% male) with daily bilateral PNP for at least 6 months (mean duration, 7.4 ± 7.8 years) received a total of six direct electrical stimulation therapies to the posterior tibial nerve at 3–4-day intervals. Eight patients completed the study and were included in the efficacy analysis. The average pain at baseline was 36.6 ± 3.80 estimated by the Short-Form McGill Pain Questionnaire. After the last stimulation, pain was significantly reduced by 85.5% to 4.88 ± 3.1 (p = 0.008). Six patients (75%) had over 50% decrease in pain after the first stimulation therapy and 99.2% after the final stimulation therapy. The patients also reported statistically significant decreases in pain level (measured by visual analog scale), ranging from 54.85% to 87.50% after each of the stimulations as compared to the pain experienced prior to the stimulations. The procedure was safe without any serious adverse events. PNS has demonstrated excellent efficacy and improvement of PNP symptoms. Further studies in larger patient populations are warranted. Keywords: peripheral nerve stimulation, posterior tibial nerve stimulation, peripheral neuropathic pain, quality of life

Paweł Sokal,1 Marek Harat,2 Piotr Zieliński,3 Sara Kierońska1 1Department of Neurosurgery, Military Research Hospital, Bydgoszcz, 2Department of Public Health, Ludwik Rydygier Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, Toruń, 3Department of Sports Medicine, University of Physical Education and Sport, Gdansk, Poland Abstract: Peripheral neuropathic pain (PNP) and complex regional pain syndrome (CRPS) can be effectively treated with peripheral nerve stimulation. In this clinical trial report, effectiveness of novel, miniature, wirelessly controlled microstimulator of tibial nerve in PNP and CRPS was evaluated. In this pilot study the average preoperative visual analog scale (VAS) score in six patients was 7.5, with 1, 3 and 6 months: 2.6 (p=0.03), 1.6 (p=0.03), and 1.3 (p=0.02), respectively. The mean average score in the six patients a week preceding the baseline visit was 7.96, preceding the 1, 3 and 6 month visits: 3.32 (p=0.043), 3.65 (p=0.045), and 2.49 (p=0.002), respectively. The average short-form McGill pain score before surgery was 23.8, and after 1, 3 and 6 months it was 11.0 (p=0.45), 6.3 (p=0.043), and 4.5 (p=0.01), respectively. Applied therapy caused a reduction of pain immediately after its application and clinical improvement was sustained on a similar level in all patients for six months. No complications of the treatment were observed. Intermittent tibial nerve stimulation by using a novel, miniature, wirelessly controlled device can be effective and feasible in PNP and CRPS. It is a safe, minimally invasive, and convenient neuromodulative method. Keywords: tibial nerve stimulation, peripheral nerve stimulation, miniature stimulator, peripheral neuropathic pain, complex regional pain syndrome

Aijun Liu, Yongcheng Jiao, Huijun Ji, Zhiwen Zhang Department of Neurosurgery, First Affiliated Hospital of PLA General Hospital, Beijing, People’s Republic of China Objectives: The aim of this study is to present a case of successful relief of bilateral occipital neuralgia (ON) using unilateral occipital nerve stimulation (ONS) and to discuss the possible underlying mechanisms. Materials and methods: We present the case of a 59-year-old female patient with severe bilateral ON treated with unilateral ONS. We systematically reviewed previous studies of ONS for ON, discussing the possible mechanisms of ONS in the relief of ON. Results: The patient reported complete pain relief after consistent unilateral ONS during the follow-up period. The underlying mechanisms may be linked to the relationship between pain and several brain regions, including the pons, midbrain, and periaqueductal gray. Conclusion: ONS is an effective and safe option for treating ON. Future studies will be required to clarify the mechanisms by which unilateral occipital stimulation provided relief for bilateral neuralgia in this case. Keywords: occipital neuralgia, neuromodulation, peripheral nerve stimulation

A 54-year-old man was admitted to the intensive care unit with an aneurysmal subarachnoid hemorrhage and subsequently underwent mechanical ventilation and received neuromuscular blocking drugs to control refractory elevated intracranial pressure. During quantitative EEG monitoring, an automated alert was triggered by the train of four peripheral nerve stimulation artifacts. Real-time feedback was made possible due to remote monitoring. This case illustrates how computerized, automated artificial intelligence algorithms can be used beyond typical seizure detection in the intensive care unit for remote monitoring to benefit patient care.

Abstract Determining a single compound maximal motor response (MMAX) or an average superimposed MMAX response (MSUP) are commonly used reference values in experiments eliciting raw electromyographic, motor evoked potentials, H‐reflexes, and V‐waves. However, existing literature is limited in detailing the most appropriate method to normalize these electrophysiological measures. Due to the accessibility of assessment from a cortical and spinal perspective, the tibialis anterior is increasingly used in literature and hence investigated in this study. The aims of the present study were to examine the differences and level of agreement in MMAX/MSUP under different muscle actions and contraction intensities. Following a familiarization session, 22 males visited the laboratory on a single occasion. MMAX was recorded under 10% isometric and 25% and 100% shortening and lengthening maximal voluntary contractions (MVC) at an angular velocity of 15° sec−1. MSUP was also recorded during 100% shortening and lengthening with an average of five responses recorded. There were no differences in MMAX or MSUP between contraction types. All variables showed large, positive correlations (P

Objective: Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates.Approach: Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses.Main Results: One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and followed stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes.Significance: These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a animal model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Together, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.

Peripheral electrical stimulation (PES), which encompasses several techniques with heterogeneous physiological responses, has shown in some cases remarkable outcomes for pain treatment and clinical rehabilitation. However, results are still mixed, mainly because there is a lack of understanding regarding its neural mechanisms of action. In this study, we aimed to assess its effects by measuring cortical activation as indexed by functional near infrared spectroscopy (fNIRS). fNIRS is a functional optical imaging method to evaluate hemodynamic changes in oxygenated (HbO) and de-oxygenated (HbR) blood hemoglobin concentrations in cortical capillary networks that can be related to cortical activity. We hypothesized that non-painful PES of accessory spinal nerve (ASN) can promote cortical activation of sensorimotor cortex (SMC) and dorsolateral prefrontal cortex (DLPFC) pain processing cortical areas. Fifteen healthy volunteers received both active and sham ASN electrical stimulation in a crossover study. The hemodynamic cortical response to unilateral right ASN burst electrical stimulation with 10 Hz was measured by a 40-channel fNIRS system. The effect of ASN electrical stimulation over HbO concentration in cortical areas of interest (CAI) was observed through the activation of right-DLPFC (p = 0.025) and left-SMC (p = 0.042) in the active group but not in sham group. Regarding left-DLPFC (p = 0.610) and right-SMC (p = 0.174) there was no statistical difference between groups. As in non-invasive brain stimulation (NIBS) top-down modulation, bottom-up electrical stimulation to the ASN seems to activate the same critical cortical areas on pain pathways related to sensory-discriminative and affective-motivational pain dimensions. These results provide additional mechanistic evidence to develop and optimize the use of peripheral nerve electrical stimulation as a neuromodulatory tool (NCT 03295370— www.clinicaltrials.gov).

Electrical stimulation of the cervical vagus nerve is an emerging treatment for inflammatory bowel disease (IBD). However, side effects from cervical vagal nerve stimulation (VNS) are often reported by patients. Here we hypothesized that stimulating the vagus nerve closer to the end organ will have fewer off-target effects and will effectively reduce intestinal inflammation. Specifically, we aimed to: (i) compare off-target effects during abdominal and cervical VNS; (ii) verify that VNS levels were suprathreshold; and (iii) determine whether abdominal VNS reduces chemically-induced intestinal inflammation in rats. An electrode array was developed in-house to stimulate and record vagal neural responses. In a non-recovery experiment, stimulation-induced off-target effects were measured by implanting the cervical and abdominal vagus nerves of anaesthetized rats (n = 5) and recording changes to heart rate, respiration and blood pressure during stimulation (10 Hz; symmetric biphasic current pulse; 320 nC per phase). In a chronic experiment, the efficacy of VNS treatment was assessed by implanting an electrode array onto the abdominal vagus nerve and recording in vivo electrically-evoked neural responses during the implantation period. After 14 days, the intestine was inflamed with TNBS (2.5% 2,4,6-trinitrobenzene sulphonic acid) and rats received therapeutic VNS (n = 7; 10 Hz; 320 nC per phase; 3 h/day) or no stimulation (n = 8) for 4.5 days. Stool quality, plasma C-reactive protein and histology of the inflamed intestine were assessed. Data show that abdominal VNS had no effect (two-way RM-ANOVA: P ≥ 0.05) on cardiac, respiratory and blood pressure parameters. However, during cervical VNS heart rate decreased by 31 ± 9 beats/minute (P ≥ 0.05), respiration was inhibited and blood pressure decreased. Data addressing efficacy of VNS treatment show that electrically-evoked neural response thresholds remained stable (one-way RM ANOVA: P ≥ 0.05) and therapeutic stimulation remained above threshold. Chronically stimulated rats, compared to unstimulated rats, had improved stool quality (two-way RM ANOVA: P < 0.0001), no blood in feces (P < 0.0001), reduced plasma C-reactive protein (two-way RM ANOVA: P < 0.05) and a reduction in resident inflammatory cell populations within the intestine (Kruskal–Wallis: P < 0.05). In conclusion, abdominal VNS did not evoke off-target effects, is an effective treatment of TNBS-induced inflammation, and may be an effective treatment of IBD in humans.

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.

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., (© 2024. The Author(s).)

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., Competing Interests: DT has a patent on the CFINE: US20140364879A1. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chowdhury and Tyler.)

The psoas muscle is the largest muscle in the lower lumbar spine and is innervated by the ipsilateral lumbar spinal nerve roots (L2-L4). Here, we present a 44-year-old female with left hip pain in the posterolateral aspect of the left hip radiating to the ipsilateral hamstring, and psoas atrophy (based on imaging). She is now reported to have over 50% improvement in pain scores after underdoing temporary peripheral nerve stimulation of the psoas muscle as well as significant improvement in muscle atrophy based on an electromyography (EMG) study. This case study is the first to report documented improvement in muscle atrophy based on EMG after peripheral nerve stimulation of the targeted area.

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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2023 World Institute of Pain.)

Phantom limb pain (PLP) is a distressing and persistent sensation that occurs after the amputation of a limb. While medication-based treatments have limitations and adverse effects, neurostimulation is a promising alternative approach whose mechanism of action needs research, including electroencephalographic (EEG) recordings for the assessment of cortical manifestation of PLP relieving effects. Here we collected and analyzed high-density EEG data in 3 patients (P01, P02, and P03). Peripheral nerve stimulation suppressed PLP in P01 but was ineffective in P02. In contrast, transcutaneous electrical nerve stimulation was effective in P02. In P03, spinal cord stimulation was used to suppress PLP. Changes in EEG oscillatory components were analyzed using spectral analysis and Petrosian fractal dimension. With these methods, changes in EEG spatio-spectral components were found in the theta, alpha, and beta bands in all patients, with these effects being specific to each individual. The changes in the EEG patterns were found for both the periods when PLP level was stationary and the periods when PLP was gradually changing after neurostimulation was turned on or off. Overall, our findings align with the proposed roles of brain rhythms in thalamocortical dysrhythmia or disruption of cortical excitation and inhibition which has been linked to neuropathic pain. The individual differences in the observed effects could be related to the specifics of each patient's treatment and the unique spectral characteristics in each of them. These findings pave the way to the closed-loop systems for PLP management where neurostimulation parameters are adjusted based on EEG-derived markers., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors declare that they have no competing interests., (© 2024 Radkowski et al.)

The treatment of neuropathic pain (NeP) often leads to partial or incomplete pain relief, with up to 40 % of patients being pharmaco-resistant. In this chapter the efficacy of neuromodulation techniques in treating NeP is reviewed. It presents a detailed evaluation of the mechanisms of action and evidence supporting the clinical use of the most common approaches like transcutaneous electrical nerve stimulation (TENS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), invasive motor cortex stimulation (iMCS), spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). Current literature suggests that motor cortex rTMS is effective for peripheral and central NeP, and TENS for peripheral NeP. Evidence for tDCS is inconclusive. DBS is reserved for research settings due to heterogeneous results, while iMSC has shown efficacy in a small randomized trial in neuropathic pain due to stroke and brachial plexus avulsion. SCS has moderate evidence for painful diabetic neuropathy and failed back surgery syndrome, but trials were not controlled with sham. DRG-S and PNS have shown positive results for complex regional pain syndrome and post-surgical neuropathic pain, respectively. Adverse effects vary, with non-invasive techniques showing local discomfort, dizziness and headache, and DBS and SCS hardware-related issues. To date, non-invasive techniques have been more extensively studied and some are included in international guidelines, while the evidence level for invasive techniques are less robust, potentially suggesting their use in a case-by-case indication considering patient´s preferences, costs and expected benefits., (Copyright © 2024. Published by Elsevier Inc.)

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.

Aim: This real-world analysis aims to quantify improvements in multiple health domains in patients who received 60-day peripheral nerve stimulation (PNS) for shoulder pain. Materials & methods: Patients reported percent pain relief and Patient Global Impression of Change in quality of life, physical function and sleep at the end of treatment (EOT), 3 months, and 6 months. Results: Of 768 patients, 80.7% were responders in at least one domain at EOT. In a subset who were followed up, a cumulative 75% continued to respond in at least one domain through 6 months (85% [n = 140/165] at 3 months and 88% [n = 53/60] at 6 months). Conclusion: 60-day PNS used for shoulder pain produced multi-dimensional improvements across health domains at EOT and through 6 months.

Background: Chronic craniofacial pain can be difficult to manage clinically. This technical report documents the peripheral nerve stimulation of the C2 dorsal root ganglion as an effective modality to treat refractory atypical facial pain., Materials and Methods: In this case series, three patients with chronic refractory atypical facial pain and p >50% pain relief following diagnostic C2 dorsal root ganglion blockade underwent ultrasound-guided percutaneous placement of a peripheral nerve stimulator adjacent to the C2 dorsal root ganglion. Patients were then observed clinically and monitored for improvement in symptoms and adverse events., Results: Three patients underwent peripheral nerve stimulator placement. At follow-up, there were no reported adverse events, and all patients reported satisfactory improvement in pain., Conclusion: The neuromodulation of C2 dorsal root ganglion via ultrasound-guided percutaneously implanted peripheral nerve stimulator is a novel and potentially effective approach for the management of chronic refractory craniofacial pain., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with an underlying cancer diagnosis may experience pain from many sources. Temporary, percutaneous peripheral nerve stimulation (PNS) is a minimally invasive procedure that can control pain in those who have failed conservative management. The purpose of this retrospective review is to show the use of PNS in managing pain in the oncologic setting., Materials and Methods: Temporary, percutaneous PNS was placed under fluoroscopic or ultrasound guidance for 15 patients at a cancer pain facility. Cases were grouped by subtypes of cancer pain (ie, tumor-related, treatment-related, cancer-associated conditions, and cancer-independent). Before PNS, patients were refractory to medical management or previous interventional treatments. Patients were observed with routine clinic visits to monitor pain levels via visual analog scale (VAS) and quality-of-life measures. PNS was removed after the indicated 60-day treatment period., Results: This retrospective review presents ten successful cases of oncologic-related pain treated with PNS. Patients with subtypes of pain that were tumor related, from cancer-associated conditions, and cancer independent all experienced a similar degree of pain relief. However, patients with cancer-treatment-related pain experienced the least analgesia from PNS. We also present six cases in which PNS did not provide adequate pain relief., Conclusion: PNS is an emerging technology in neuromodulation that may be useful in managing pain, especially in the oncologic population. Patients with cancer-related and non-cancer-related pain localized to a specific nerve distribution should be considered appropriate candidates for PNS. Further research is needed to optimize patient selection and indications for PNS in the population with cancer., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Peripheral neuropathy has several causes, with diabetes being the most common. Conservative management may fail to control pain. Our study aimed at evaluating the use of peripheral nerve stimulation of the posterior tibial nerve for treating peripheral neuropathy., Materials and Methods: This was an observational study of 15 patients who received peripheral nerve stimulation at the posterior tibial nerve to treat peripheral neuropathy. Outcomes measured were improvement of pain scores and Patient Global Impression of Change (PGIC) at 12 months compared with before the implant., Results: Mean pain scores with the verbal rating scale were 3 ± 1.8 at >12 months compared with 8.6 ± 1.2 at baseline, a reduction of 65% (p < 0.001). Median satisfaction with the PGIC at >12 months was 7 of 7, with most subjects reporting a 6 (better) or a 7 (a great deal better)., Conclusion: Peripheral nerve stimulation of the posterior tibial nerve can be a safe and effective modality for treating chronic pain symptoms related to peripheral neuropathy of the foot., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The percutaneous technique of electrode insertion in the vicinity of the greater occipital nerves to treat occipital neuralgia was first described in the 1990s by Weiner and Reed. This subsequently stimulated awareness of peripheral nerve stimulation (PNS). The more recent advent emergence of a minimally invasive percutaneous approach by way of using ultrasound has further increased the interest in PNS as a viable alternative to more invasive techniques. PNS has become more popular recently and is increasingly used to treat various pain conditions. Its foundation is fundamentally based on the gate control theory, although the precise mechanism underlying its analgesic effect is still indefinite. Studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and the involvement of the cortical and subcortical areas. Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the modulation of PNS mechanisms can help guide stimulation approaches and parameters to optimize the use of PNS. his chapter aims to review the background and mechanisms of PNS modulation. PNS is becoming one of the most diverse therapies in neuromodulation due to rapid evolution and expansion. It is an attractive option for clinicians due to the simplicity and versatility of procedures that can be combined with other neuromodulation treatments or used alone. It has a distinct role in the modulation of functional conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This case report presents an application of percutaneous peripheral nerve stimulation to the right superficial peroneal nerve to treat a patient with chronic intractable L5–S1 radiculopathy pain that conventional treatment failed to ameliorate. Methods: The patient underwent an uneventful implantation of a percutaneous peripheral nerve stimulator. The implanted lead (15 cm in length and 1.2 mm in diameter) containing the receiver coil and 3 stimulation electrodes (Bioness Stimrouter®, Valencia, CA, U.S.A.) was implanted parallel with the trajectory of the right superficial peroneal nerve. Results: Two weeks after implantation of the percutaneous peripheral nerve stimulator, the patient experienced excellent pain relief and reported a significant increase in mobility. At the 3‐month follow‐up consultation, the patient reported maintenance of the reduction of pain in his right lower extremity as well as improved performance in his daily activities. Conclusion: Percutaneous peripheral nerve stimulation offers an alternative treatment option for intractable pain associated with chronic radiculopathy, especially for patients in whom conventional treatment options have been exhausted. Further clinical series involving larger numbers of patients are warranted in order to assess the definitive role of percutaneous peripheral nerve stimulation for the treatment of chronic intractable radiculopathy pain. [ABSTRACT FROM AUTHOR]

Improved understanding of the monitoring and dosing practices of anesthesia providers regarding neuromuscular blockade is necessary. The use of subjective methods such as peripheral nerve stimulation and clinical assessment tests can increase the risk of residual neuromuscular blockade and adverse postoperative outcomes. Quantitative monitoring of neuromuscular blockade is an alternative tool to peripheral nerve stimulation to guide neuromuscular blockade; however, it is rarely used by providers. We developed an initiative to improve anesthesia providers' knowledge of neuromuscular blockade pharmacology, physiology, monitoring, and management. After the initiative, an analysis assessed for practice change regarding the use of quantitative monitoring and dosing of neuromuscular blocking agents and neostigmine. The use of quantitative monitoring increased significantly from 14.0% in the preinitiative group to 48.0% after the initiative (P < .001). The least squares mean 95% effective dose (ED95) neuromuscular blocking agents dose was compared between pre-initiative and postinitiative groups, and case length was a significant predictor for patients receiving the highest neuromuscular blocking agents doses. Neostigmine doses were compared between preinitiative and postinitiative groups, and body mass index was a significant predictor of the least squares mean neostigmine dose (P = .002) and the likelihood of receiving a high neostigmine dose (odds ratio = 0.911, 95% CI = 0.870-0.955). [ABSTRACT FROM AUTHOR]

Background: Complex regional pain syndrome (CRPS) is a chronic disabling painful disorder with limited options to achieve therapeutic relief. CRPS type I which follows trauma, may not show obvious damage to the nervous structures and remains dubious in its pathophysiology and also its response to conservative treatment or interventional pain management is elusive. Spinal cord and dorsal root ganglion stimulation (SCS, DRGS) provide good relief, mainly for causalgia or CRPS I of lower extremities but not very encouraging for upper extremity CRPS I. we reported earlier, a case of CRPS I of right arm treated successfully by wireless peripheral nerve stimulation (WPNS) with short term follow up. Here we present 1-year follow-up of this patient. Objective: To present the first case of WPNS for CRPS I with a year follow up. The patient had minimally invasive peripheral nerve stimulation (PNS), without implantable pulse generator (IPG) or its accessories. Case report: This was a case of refractory CRPS I after blunt trauma to the right forearm of a young female. She underwent placement of two Stimwave electrodes (Leads: FR4A-RCV-A0 with tines, Generation 1 and FR4A-RCV-B0 with tines, Generation 1) in her forearm under intraoperative electrophysiological and ultrasound guidance along radial and median nerves. This WPNS required no IPG. At high frequency (HF) stimulation (HF 10 kHz/32 μs, 2.0 mA), patient had shown remarkable relief in pain, allodynia and temperature impairment. At 5 months she started driving without opioid consumption, while allodynia disappeared. At 1 year follow up she was relieved of pain [visual analogue scale (VAS) score of 4 from 7] and Kapanji Index (Score) improved to 7–8. Both hands look similar in color and temperature. She never made unscheduled visits to the clinic or visited emergency room for any complications related to the WPNS. Conclusions: CRPS I involving upper extremity remain difficult to manage with conventional SCS or DRGS because of equipment related adverse events. Minimally invasive WPNS in this case had shown consistent relief without any complications or side effects related to the wireless technology or the technique at the end of 1 year. Implications: This is the first case illustration of WPNS for CRPS I, successfully treated and followed up for 1 year. [ABSTRACT FROM AUTHOR]

Prosthetic hands, today, have anthropomorphic, multifinger design. A common control method uses pattern recognition of electromyogram signals. However, these prostheses do not capture the human hand’s sensory perception, which is critical for prosthesis embodiment and dexterous object manipulation. This problem can be solved by sensorized electronic skin (e-skin) composed of various sensors that transduce sensory percepts such as touch, pressure, temperature, and pain, just as human skin does. This review will present the physiology of the receptors that encode tactile, thermal, nociceptive, and proprioceptive information. The e-skin is designed to mimic these receptors and their responses. We review each sensor subtype, and its design and performance when embedded in the e-skin. Next, we review the spiking response of the receptors, which are then relayed to sensory nerves and encoded by the brain as sensory percepts. The e-skin system is designed to produce neuromorphic or receptorlike spiking activity. Computational models to mimic these sensory nerve signals are presented and then various methods to interface with the nervous system are explored and compared. We conclude the review with the state of the art in e-skin design and deployment in closed-loop applications that demonstrate the benefits of sensory feedback for amputees. [ABSTRACT FROM AUTHOR]

Peripheral nerve blocks (PNBs) using local anesthetics either via single injection or continuous perineural catheter have been the mainstay for regional anesthesia and are a vital component of postoperative multimodal opioid-sparing pain management. There are some limitations to PNBs, however, mainly its limited duration of action, but also risk of catheter-associated infection and dislodgements. Furthermore, local anesthetic-based blocks can induce sensory deficits and motor weakness, possibly increasing the risk of falling and/or decreasing the ability to participate in postoperative rehabilitation. In this review, we first discuss various local anesthetic-based PNB techniques for major surgery and then review newer modalities, including liposome bupivacaine, cryoanalgesia, and peripheral nerve stimulation; all of which may offer advantages over single and continuous local anesthetic-based PNBs. [ABSTRACT FROM AUTHOR]

Objective: Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates. Approach: Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses. Main Results: One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and followed stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes. Significance: These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a animal model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Together, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain and reduced function are significant problems for Military Service members and Veterans following amputation. Peripheral nerve stimulation (PNS) is a promising therapy, but PNS systems have traditionally been limited by invasiveness and complications. Recently, a novel percutaneous PNS system was developed to reduce the risk of complications and enable delivery of stimulation without surgery.Materials and Methods: Percutaneous PNS was evaluated to determine if stimulation provides relief from residual and phantom limb pain following lower-extremity amputation. PNS leads were implanted percutaneously to deliver stimulation to the femoral and/or sciatic nerves. Patients received stimulation for up to 60 days followed by withdrawal of the leads.Results: A review of recent studies and clinical reports found that a majority of patients (18/24, 75%) reported substantial (≥50%) clinically relevant relief of chronic post-amputation pain following up to 60 days of percutaneous PNS. Reductions in pain were frequently associated with reductions in disability and pain interference.Conclusions: Percutaneous PNS can durably reduce pain, thereby enabling improvements in quality of life, function, and rehabilitation in individuals with residual or phantom limb pain following amputation. Percutaneous PNS may have additional benefit for Military Service members and Veterans with post-surgical or post-traumatic pain. [ABSTRACT FROM AUTHOR]