Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Use of Temporary Percutaneous Peripheral Nerve Stimulation in an Oncologic Population: A Retrospective Review.

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.

The Untold Story of Occipital Nerve Stimulation in Patients With Cluster Headache: Surgical Technique in Relation to Clinical Efficacy.

OBJECTIVES: Approximately one in every 1000 adults experiences cluster headache (CH). Although occipital nerve stimulation (ONS) appears encouraging in treatment for most patients with refractory CH, some patients do not reach adequate pain relief with ONS. A reason for failure of ONS might be anatomical variations and different surgical approaches. Therefore, an extensive literature analysis was performed, and cadaveric experimentation was combined with our clinical experience to provide a standardized proposal for ONS and obtain optimal management of patients with refractory CH. MATERIALS AND METHODS: Data from 36 articles published between 1998 and 2023 were analyzed to retrieve information on the anatomical landmarks and surgical technique of ONS. For the cadaveric experimentation (N = 1), two electrodes were inserted from the region over the foramen magnum and projected toward the lower third of the mastoid process. RESULTS: The existence of multiple approaches of ONS has been confirmed by the present analysis. Discrepancies have been found in the anatomical locations and corresponding landmarks of the greater and lesser occipital nerve. The surgical approaches differed in patient positioning, electrode placement, and imaging techniques, with an overall efficacy range of 35.7% to 90%. CONCLUSIONS: Reports on the surgical approach of ONS remain contradictory, hence emphasizing the need for standardization. Only if all implanting physicians perform the ONS surgery using a standardized protocol, can future data be combined and outcomes compared and analyzed.

Peripheral Nervous System Pain Modulation.

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.

Photobiomodulation and Vascularization in Conduit-Based Peripheral Nerve Repair: A Narrative Review.

Background: Peripheral nerve injuries pose a significant clinical issue for patients, especially in the most severe cases wherein complete transection (neurotmesis) results in total loss of sensory/motor function. Nerve guidance conduits (NGCs) are a common treatment option that protects and guides regenerating axons during recovery. However, treatment outcomes remain limited and often fail to achieve full reinnervation, especially in critically sized defects (>3 cm) where a lack of vascularization leads to neural necrosis. Conclusions: A multitreatment approach is, therefore, necessary to improve the efficacy of NGCs. Stimulating angiogenesis within NGCs can help alleviate oxygen deficiency through rapid inosculation with the host vasculature, whereas photobiomodulation therapy (PBMT) has demonstrated beneficial therapeutic effects on regenerating nerve cells and neovascularization. In this review, we discuss the current trends of NGCs, vascularization, and PBMT as treatments for peripheral nerve neurotmesis and highlight the need for a combinatorial approach to improve functional and clinical outcomes.

Application of a physiotherapeutic protocol associated with photobiomodulation for the treatment of leprosy patients.

Leprosy is a chronic infectious disease characterized by acute inflammatory episodes that affect the skin and peripheral nerves and can develop progressive and irreversible disabilities and deformities. In addition, drug therapy and physiotherapy offer resources and techniques capable of mitigating the consequences of neural lesions, but neural lesions can occur before, during, and even after drug treatment. Thus, new treatments are needed. Photobiomodulation (PBM) might be a promissor therapy since it aims to reduce the inflammatory process and restore motor and sensory functions in the affected area. This study aims to compare the evolution of neural status, pain, and functionality in patients with leprosy and neuritis after a physiotherapeutic protocol and PBM treatment. This was a randomized controlled clinical trial that analyzed a group of patients receiving a physiotherapeutic protocol (PPG) and another receiving physiotherapeutic protocol associated with PBM (PLG) (wavelength 904 nm, potency 70 mW, time per point 9 s). Our results showed when evaluating functional capacity limitations with the SALSA scale, the PLG patients improved from moderate to mild limitations. On the other hand, the PPG remained as moderate limitations. Also, the PLG showed a significant reduction in pain on the VAS scale. The neurological assessment showed that PLG improved palpation of the median, radial, and peroneal nerves. In the strength test, PLG patients improved in the 5th finger abduction and ankle dorsiflexion. Assessing sensitivity, it was identified an improvement in PLG for the ulnar nerve and tibial nerve. All those changes were statistically significant when compared to the PPG patients. Finally, the PLG patients improved disabilities, identified by the neurological assessment of the eyes, hands, and feet. In conclusion, this study demonstrated that combining a physiotherapeutic protocol with PBM treatment effectively improved functional status and reduced pain in leprosy patients.

Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation.

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.

Peripheral nerve stimulation for chronic knee pain following total knee arthroplasty: a systematic review.

Chronic knee pain following total knee arthroplasty (TKA) affects a subset of patients that is refractory to pharmacological and non-pharmacological modalities. Peripheral nerve stimulation (PNS) has been used in patients with chronic knee pain following TKA and has shown some efficacy. Methods: Comprehensive search of Ovid Medline, Elsevier Embase, Cochrane Central Register of Controlled Trials, CINAHL Plus with Full Text, Scopus, SPORTDiscus with Full Text and the Web of Science platform. From inception to August 2022, for studies using PNS to treat chronic knee pain following TKA. Primary outcomes included pain scores, functional status and medication usage. Results: Nine studies were extrapolated with all demonstrating effectiveness of PNS for patients with chronic knee pain following TKA. Discussion: PNS for chronic knee pain following TKA has been shown to be an efficacious treatment modality. The level of evidence is low and more research is needed to assess its safety and effectiveness.

Peripheral Nerve Stimulation for the Management of Pediatric Neuropathic Pain.

The management of neuropathic pain in children poses an enormous challenge for pediatricians and pain management physicians. Current treatment options include physical therapy and medication management. Peripheral nerve stimulation/neuromodulation is a novel and minimally invasive treatment that can be initiated and monitored in an outpatient setting. This new technology can be a useful tool for treating pain secondary to pediatric neuropathy and chronic refractory pain after conservative management. Our case report describes the use of a peripheral nerve stimulator in the successful management of pediatric neuropathic leg pain.

The Emerging Role of Peripheral Nerve Stimulation in Postoperative Analgesia.

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. 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.

Avian riboflavin deficiency causes reliably reproducible peripheral nerve demyelination and, with vitamin supplementation, rapid remyelination.

Riboflavin deficiency produces severe peripheral neve demyelination in young, rapidly growing chickens. While this naturally-occurring vitamin B2 deficiency can cause a debilitating peripheral neuropathy, and mortality, in poultry flocks, it can also be a useful experimental animal model to study the pathogenesis of reliably reproducible peripheral nerve demyelination. Moreover, restitution of normal riboflavin levels in deficient birds results in brisk remyelination. It is the only acquired, primary, demyelinating tomaculous neuropathy described to date in animals. The only other substance that causes peripheral nerve demyelination similar to avian riboflavin deficiency is tellurium and the pathologic features of the peripheral neuropathy produced by this developmental neurotoxin in weanling rats are also described.

Peripheral Nerve Stimulation for Pain Management: A Review.

PURPOSE OF REVIEW: Peripheral nerve stimulation has seen a recent upsurge in utilization for various chronic pain conditions, specifically from a neuropathic etiology, where a single peripheral nerve can be pinpointed as a culprit for pain. RECENT FINDINGS: There is conflicting evidence about the efficacy and long-term outcomes of peripheral nerve stimulation for chronic pain, with most studies being small sized. The focus of this article is to review available evidence for the utilization of peripheral nerve stimulation for chronic pain syndromes as well as upcoming evidence in the immediate postoperative realm. The indications for the use of PNS have expanded from neuropathic pain such as occipital neuralgia and post-amputation pain, to more widespread disease processes such as chronic low back pain. Percutaneous PNS delivered over a 60-day period may provide significant carry-over effects including pain relief, potentially avoiding the need for a permanently implanted system while enabling improved function in patients with chronic pain.

Topical borneol relieves nonhistaminergic pruritus via targeting TRPA1 and TRPM8 channels in peripheral nerve terminals of mice.

Borneol has been used successfully for the treatment of itchy skin in traditional Chinese medicine. However, the antipruritic effect of borneol has rarely been studied, and the mechanism is unclear. Here, we showed that topical application of borneol on skin substantially suppressed pruritogen chloroquine- and compound 48/80-induced itching in mice. The potential targets of borneol, including transient receptor potential cation channel subfamily V member 3 (TRPV3), transient receptor potential cation channel subfamily A member 1 (TRPA1), transient receptor potential cation channel subfamily M member 8 (TRPM8), and gamma-aminobutyric acid type A (GABAA) receptor were pharmacologically inhibited or genetically knocked out one by one in mouse. Itching behavior studies demonstrated that the antipruritic effect of borneol is largely independent of TRPV3 and GABAA receptor, and TRPA1 and TRPM8 channels are responsible for a major portion of the effect of borneol on chloroquine-induced nonhistaminergic itching. Borneol activates TRPM8 and inhibits TRPA1 in sensory neurons of mice. Topical co-application of TRPA1 antagonist and TRPM8 agonist mimicked the effect of borneol on chloroquine-induced itching. Intrathecal injection of a group II metabotropic glutamate receptor antagonist partially attenuated the effect of borneol and completely abolished the effect of TRPM8 agonist on chloroquine-induced itching, suggesting that a spinal glutamatergic mechanism is involved. In contrast, the effect of borneol on compound 48/80-induced histaminergic itching occurs through TRPA1-and TRPM8-independent mechanisms. Our work demonstrates that borneol is an effective topical itch reliever, and TRPA1 inhibition and TRPM8 activation in peripheral nerve terminals account for its antipruritic effect.

The role of peripheral nerve stimulation in refractory non-operative chronic knee osteoarthritis.

Aim: This case series aimed to analyze the efficacy of a temporary peripheral nerve stimulation (PNS) device implanted for 60 days at 60 days post-explant for patients with non-surgical osteoarthritic knee pain. Patients & methods: 19 patients were selected for treatment with temporary PNS at an outpatient pain management clinic. Results: Patients demonstrated improvement in their knee pain from baseline post-temporary PNS explant (p = 0.973). Conclusion: Temporary PNS serves as a promising therapy for patients with limited options for therapy, necessitating further high-quality studies.

Temporary peripheral nerve stimulation (PNS) is a treatment for patients with knee swelling and pain who can't get surgery. The authors studied temporary PNS to see if the patient's knee pain improved. 19 patients were treated with temporary PNS. The study found the patients' knee pain improved after completing the treatment. More research is needed in the future to temporary PNS in knee pain patients.

A Retrospective Review of Real-world Outcomes Following 60-day Peripheral Nerve Stimulation for the Treatment of Chronic Pain.

BACKGROUND: Real-world data can provide important insights into treatment effectiveness in routine clinical practice. Studies have demonstrated that in multiple different pain indications temporary (60-day) percutaneous peripheral nerve stimulation (PNS) treatment can produce significant relief, but few real-world studies have been published. The present study is the first real-world, retrospective review of a large database depicting outcomes at the end of a 60-day PNS treatment period. OBJECTIVES: Evaluate outcomes during a 60-day PNS treatment in routine clinical practice. STUDY DESIGN: Secondary retrospective review. METHODS: Anonymized records of 6,160 patients who were implanted with a SPRINT PNS System from August 2019 through August 2022 were retrospectively reviewed from a national real-world database. The percentage of patients with ? 50% pain relief and/or improvement in quality of life was evaluated and stratified by nerve target. Additional outcomes included average and worst pain score, patient-reported percentage of pain relief, and patient global impression of change. RESULTS: Overall, 71% of patients (4,348/6,160) were responders with >= 50% pain relief and/or improvement in quality of life; pain relief among responders averaged 63%. The responder rate was largely consistent across nerve targets throughout the back and trunk, upper and lower extremities, and posterior head and neck. LIMITATIONS: This study was limited by its retrospective nature and reliance on a device manufacturer's database. Additionally, detailed demographic information and measures for pain medication usage and physical function were not assessed. CONCLUSIONS: This retrospective analysis supports recent prospective studies demonstrating that 60-day percutaneous PNS can provide significant relief across a wide range of nerve targets. These data serve an important role in complementing the findings of published prospective clinical trials.

Role of neuromodulation in acute pain settings.

Peripheral nerve stimulation (PNS), a type of neuromodulatory technique, is increasingly used to treat chronic pain syndromes. PNS has also recently gained popularity as a viable adjunct analgesic modality in acute pain settings, where the practice primarily relies on using boluses or infusion of local anesthetics for nerve blockade, followed by stimulation to extend the analgesia. There is some early promise in PNS for perioperative analgesic control, but considerable obstacles must be addressed before it can be implemented into standard practice. In this daring discourse, we explore the possibilities and constraints of using the PNS paradigm in acute pain.

Role of peripheral nerve stimulation in treating chronic neuropathic pain: an international focused survey of pain medicine experts.

Interventional pain management (IPM) options for refractory neuropathic pain (NP) have recently increased with availability of peripheral nerve stimulation (PNS) equipment and expertise. Given a lack of high-quality evidence and guidelines on this topic, we sought to understand the perception of physicians with expertise in treating NP regarding IPM and the role of PNS. We emailed a survey in March 2022 to international NP experts including pain medicine physicians, researchers, and leaders of 11 professional pain societies. No representatives from vendors of PNS systems were included in the design of the survey nor as respondents. Among 24 respondents (67% of those contacted), the distal common peroneal, tibial, and sural nerves were most frequently targeted (60%) with PNS. Persistent postsurgical pain of more than 3 months was the most common indication for PNS (84%). The aggregate NP treatment algorithm in order of median rank was non-opioid medications as first line, IPM including epidural/perineural steroid injections tied with transcutaneous electrical nerve stimulation as second line, pulsed radiofrequency (RF) tied with RF ablation/denervation as third line, temporary then permanent PNS as fourth line, followed by spinal cord stimulation, opioids, cryoablation, botulinum, peripheral nerve field stimulation, intrathecal targeted drug delivery, and others. Before offering PNS, 12 respondents (50%) indicated their preference for trialing non-neuromodulation treatments for 1-3 months. Twenty-two respondents (92%) agreed PNS should be offered early in the treatment of neuropathic pain. The most common barriers to PNS use were cost, lack of high-quality evidence in support of its use, lack of exposure to PNS in training programs, and lack of familiarity with the use of ultrasound guidance. PNS appears to have an increasing role in the treatment of NP but more research is needed on the outcomes of PNS to elucidate its role.

Peripheral Nerve Stimulation for Low Back Pain: A Systematic Review.

PURPOSE OF REVIEW: Low back pain (LBP) is a prevalent condition that is associated with diminished physical function, poor mental health outcomes, and reduced quality of life. Peripheral nerve stimulation (PNS) is an emerging modality that has been utilized to treat LBP. The primary objective of this systematic review is to appraise the level of evidence on the efficacy of PNS for treatment of LBP. RECENT FINDINGS: Twenty-nine articles were included in this systematic review, consisting of 828 total participants utilizing PNS as the primary modality for LBP and 173 participants using PNS as salvage or adjunctive therapy for LBP after SCS placement. Different modalities of PNS therapy were reported across studies, including conventional PNS systems stimulating the lumbar medial branch nerves, peripheral nerve field stimulation (PNFS), and restorative neuromuscular stimulation of the multifidus muscles. All studies consistently reported positive modest to moderate improvement in pain intensity with PNS therapy when comparing baseline pain intensity to each study's respective primary follow-up period. There was a very low GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) quality of evidence supporting this finding. Inconsistency was present in some comparative studies that demonstrated no difference between PNS therapy versus control cohorts (sham or SCS therapy alone), which therefore highlighted the potential for placebo effect. This systematic review highlights that PNS, PNFS, and neuromuscular stimulation may provide modest to moderate pain relief in patients with LBP, although evidence is currently limited due to risk of bias, clinical and methodological heterogeneity, and inconsistency in data.

Peripheral nerve stimulation enables somatosensory feedback while suppressing phantom limb pain in transradial amputees.

To simultaneously treat phantom limb pain (PLP) and restore somatic sensations using peripheral nerve stimulation (PNS), two bilateral transradial amputees were implanted with stimulating electrodes in the proximity of the medial, ulnar and radial nerves. Application of PNS evoked tactile and proprioceptive sensations in the phantom hand. Both patients learned to determine the shape of invisible objects by scanning a computer tablet with a stylus while receiving feedback based on PNS or transcutaneous electrical nerve stimulation (TENS). Оne patient learned to use PNS as feedback from the prosthetic hand that grasped objects of different sizes. PNS abolished PLP completely in one patient and reduced it by 40-70% in the other. We suggest incorporating PNS and/or TENS in active tasks to reduce PLP and restore sensations in amputees.