Search Results (254)

Electroactive biomaterials are a key emerging technology for the treatment of neural damage. Conducting polymer-coated carbon microfibers are particularly useful for this application because they provide directional support for cell growth and tissue repair and simultaneously allow for ultrasensitive recording and stimulation of neural activity. Here, we report in vitro experiments investigating the biology of Schwann cells (SCs), a major player in peripheral nerve regeneration, on electroconducting microfibers. The optimal molecular composition of the cell substrate and cell culture medium was studied for SCs dissociated from rat and pig peripheral nerves. The substrate molecules were then attached to carbon microfibers coated with poly (3,4-ethylenedioxythiophene) doped with poly [(4-styrenesulfonic acid)-co-(maleic acid)] (PCMFs), which served as an electroactive scaffold for culturing nerve explants. Biphasic electrical stimulation (ES) was applied through the microfibers, and its effects on cell proliferation and migration were assessed in different cell culture media. Rodent and porcine SCs avidly migrated on PCMFs functionalized with a complex of poly-L-lysine, heparin, basic fibroblast growth factor, and fibronectin. Serum and forskolin/heregulin increased, by two-fold and four-fold, the number of SCs on PCMFs, respectively, and ES further doubled cell numbers without favoring fibroblast proliferation. ES additionally increased SC migration. These results provide a baseline for using biofunctionalized PCMFs in peripheral nerve repair. Full article

Background: Peripheral nerve stimulation (PNS) has been employed as a therapeutic modality for managing chronic pain across diverse etiologies and neural targets. Nevertheless, its application in treating chronic axial neck pain remains markedly underexplored. Accordingly, this study aimed to both review the existing literature and present a retrospective single-center case series of patients who underwent temporary PNS targeting the cervical medial branch nerves (CMBNs) for chronic axial neck pain. Methods: This investigation comprises a narrative literature review alongside a single-center, retrospective case series evaluating percutaneous, temporary PNS for the management of cervical spondylosis facet arthropathy in the absence of myelopathy or radiculopathy. The primary outcomes were pain reduction, as measured by the numeric rating scale, and improvements in functional disability, with assessments conducted at baseline and at 60 days post-intervention. Results: PNS represents a neuromodulatory, nondestructive intervention that targets the CMBN to alleviate chronic axial neck pain, in contrast to the destructive mechanisms inherent in cervical radiofrequency ablation (CRFA). Although PNS has been applied to other neural targets, its use in the cervical region is sparsely documented, with limited case studies available. Notably, this case series is the first to report pain and disability outcomes specifically associated with CMBN PNS. At the 60-day follow-up, 66% of subjects achieved the minimal clinically important difference (MCID) for pain reduction, while 77% met the MCID for disability reduction. Moreover, our analysis uniquely examined the impact of previous CRFA and a history of cervical spine surgery on treatment outcomes, revealing that patients with such interventions experienced more modest improvements compared to their surgery- and CRFA-naive counterparts. Conclusions: The current literature reveals a significant gap regarding the use of CMBN PNS, underscoring an unmet need in the treatment algorithm for chronic axial neck pain beyond conservative modalities. Our findings suggest that CMBN PNS may offer a promising adjunctive therapy for carefully selected patients with refractory chronic axial neck pain who have not improved after medications, physical therapy, or injections. Additionally, the comparative analysis of outcomes in patients with a history of CRFA or cervical surgery underscores potential advantages of PNS prior to destructive therapies. Future research, ideally in the form of prospective studies with larger cohorts and extended follow-up durations, is warranted to further evaluate long-term outcomes and refine the place of PNS in the treatment algorithm. Full article

Giant somatosensory evoked potentials (gSEPs) are abnormally high-amplitude cortical responses to peripheral nerve stimulation, traditionally regarded as electrophysiological hallmarks of progressive myoclonic epilepsies (PMEs). However, accumulating evidence shows their presence in a broader range of non-epileptic conditions, including focal lesions, metabolic encephalopathies, neurodegenerative diseases, and even functional disorders. This review offers a comprehensive analysis of the physiological mechanisms, diagnostic criteria, and clinical significance of gSEPs, integrating data from both classical and emerging neurophysiological techniques. gSEPs are mainly produced in the primary somatosensory cortex through mechanisms involving cortical disinhibition, impaired GABAergic transmission, and altered thalamocortical connectivity. In epileptic syndromes such as Unverricht–Lundborg disease and other PMEs, gSEPs reflect cortical hyperexcitability and are closely linked to cortical myoclonus. Conversely, in non-epileptic contexts, they may indicate transient or chronic cortical dysfunction. The diagnostic utility of gSEPs ranges from differential diagnosis of myoclonus to monitoring disease. However, heterogeneity in amplitude definitions and recording protocols hinders the standardization of these measurements. This may result in the identification of the right threshold to differentiate conditions associated with simple increased versus giant SEP, the latter of which may help identify truly epileptic conditions from other disorders simply associated with increased SEP amplitude. Full article

Background and Clinical Significance: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and limiting complication of oncological treatment, particularly in patients receiving oxaliplatin. Its onset can significantly affect the quality of life and compromise the continuity of the antineoplastic therapy. Due to the limited efficacy of available pharmacological therapies, percutaneous electrical nerve stimulation (PENS) has been proposed as a non-invasive alternative for symptom management. Case presentation: We report the case of a 75-year-old woman with colorectal adenocarcinoma who developed CIPN following oxaliplatin administration. She underwent a 12-week course of PENS targeting the median nerve, with weekly sessions conducted without interruption of chemotherapy and without adverse effects. The patient showed progressive improvement in neurosensory symptoms, as measured by the EORTC QLQ-CIPN20 questionnaire. Quantitative sensory testing revealed normalization of thermal and vibratory sensitivity and improved mechanical detection thresholds. The cumulative oxaliplatin dose was maintained throughout treatment. Conclusions: PENS may offer an effective and safe therapeutic option for managing CIPN, enabling symptom control without compromising oncological treatment. This case supports the need for controlled clinical trials to confirm efficacy and establish standardized protocols. Full article

Objectives: This study aimed to investigate the efficacy of Percutaneous Electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS), and Eccentric Exercise (EE) in patients with supraspinatus tendinopathy. Methods: Forty-six participants with supraspinatus tendinopathy were randomly allocated to either an invasive therapy group (four sessions in four weeks of PE+PNS and EE program) or a conventional physical therapy group (ten sessions for 2 weeks). The multimodal physical program included Ultrasound therapy (US), Transcutaneous Electric Nerve Stimulation (TENS) and the same EE program. The Numerical Pain Rating Scale (NPRS), shoulder Range of Motion (ROM), Pressure Pain Threshold (PPT), and disability (DASH and SPADI) were measured at baseline, at the end of treatment, and at 12- and 24-weeks follow-up. Results: The PE+PNS+EE group demonstrated consistently greater and statistically significant improvements across nearly all pain, mobility, and functional outcomes at all follow-up points (post-treatment, 12-weeks, and 24-weeks) compared to the TENS+US+EE group, with generally medium to large effect sizes. Conclusions: This study concludes that the combined PE+PNS+EE intervention offers safe and effective treatment for supraspinatus tendinopathy, demonstrating statistically significant improvements in pain, mobility, and function compared to conventional electrotherapy. Full article

Pulsed radiofrequency (PRF) current applied to peripheral nerves is a modality used in interventional pain medicine, but its underlying mechanisms remain unclear. This study aimed to investigate whether ex vivo exposure of human monocytic THP-1 cells to PRF current or to heat induces β-endorphin production. Methods: THP-1 cells were exposed to PRF current for 15 min or incubated at elevated temperatures (42 °C to 50 °C) for 3 or 15 min. Flow cytometry was used to assess cell viability, and β-endorphin concentrations in culture supernatants were quantified by ELISA. In a separate experiment, cells were stimulated with lipopolysaccharide (LPS) to compare its effects on β-endorphin release. Results: A 3 min exposure to temperatures ≥ 46 °C reduced THP-1 cell viability, whereas a 15 min exposure to PRF current or to heat at 42 °C did not impair viability. Both PRF current and mild heat significantly enhanced β-endorphin release. β-Endorphin levels in the supernatant of LPS-stimulated cells were comparable to those of cells exposed to PRF current. Conclusions: Ex vivo application of PRF current or mild heat enhanced β-endorphin production from THP-1 cells without significant cytotoxicity. These preliminary findings warrant further investigation using primary human monocytes and in vivo models to assess therapeutic potential. Full article

Objective: Given the side effects and reduced efficacy of conventional local anesthetics in inflammatory conditions, there is a compelling need for complementary alternative medicine (CAM), particularly those based on phytochemicals. While a previous study showed that in vivo local injection of (-)-epigallocatechin-3-gallate (EGCG) into the peripheral receptive field suppresses the excitability of rat trigeminal ganglion (TG) neurons in the absence of inflammation, the acute effects of EGCG in vivo, especially on TG neurons under inflammatory conditions, are still unknown. We aimed to determine if acute local EGCG administration into inflamed tissue effectively attenuates the excitability of nociceptive TG neurons evoked by mechanical stimulation. Methods: The escape reflex threshold was measured to assess hyperalgesia caused by complete Freund’s adjuvant (CFA)-induced inflammation. To assess neuronal activity, extracellular single-unit recordings were performed on TG neurons in anesthetized CFA-inflamed rats in response to orofacial mechanical stimulation. Results: The mechanical escape threshold was significantly lower in CFA-inflamed rats compared to before CFA injection. EGCG (1–10 mM) reversibly and dose-dependently inhibited the mean firing frequency of TG neurons evoked by both non-noxious and noxious mechanical stimuli (p < 0.05). For comparison, 1% lidocaine (37 mM), a local anesthetic, also caused reversible inhibition of the mean firing frequency in inflamed TG neurons responding to mechanical stimuli. Importantly, 10 mM EGCG produced a significantly greater magnitude of inhibition on TG neuronal discharge frequency than 1% lidocaine (noxious, lidocaine vs. EGCG, 19.7 ± 3.3% vs. 42.3 ± 3.4%, p < 0.05). Conclusions: Local injection of EGCG into inflamed tissue effectively suppresses the excitability of nociceptive primary sensory TG neurons, as indicated by these findings. Significantly, locally administered EGCG exerted a more potent local analgesic action compared to conventional voltage-gated sodium channel blockers. This heightened efficacy originates from EGCG’s ability to inhibit both generator potentials and action potentials directly at nociceptive primary nerve terminals. As a result, EGCG stands out as a compelling candidate for novel analgesic development, holding particular relevance for CAM strategies. Full article

Postamputation pain (PAP), including residual limb pain (RLP) and phantom limb pain (PLP), remains a significant and debilitating complication after limb loss. Despite advances in pharmacological management, many patients experience inadequate pain relief, underscoring the need for alternative therapeutic strategies. Objective: This narrative review critically synthesizes current interventional therapies for PAP, focusing on mechanisms, clinical efficacy and practical application. Methods: A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science databases for studies published between 2015 and 2025. Relevant articles on peripheral nerve interventions as well as different neuromodulation techniques were included. Results: Peripheral interventions (such as alcohol neurolysis, radiofrequency ablation (RFA) and cryoneurolysis (CNL)) and neuromodulation techniques (including spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation and cauda equina stimulation (CES)) demonstrate promising outcomes for PAP. Peripheral nerve stimulation (PNS) shows favorable safety and efficacy profiles and may help prevent the chronification of pain. Conclusions: Contemporary interventional therapies represent valuable options in the multidisciplinary management of PAP. Nevertheless, further research is required to standardize clinical algorithms, optimize therapeutic decision-making and improve long-term outcomes and quality of life for individuals with PAP. Full article

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

Neurophysiological techniques, particularly somatosensory evoked potentials (SEPs) and electroencephalography (EEG), are essential tools for the functional and prognostic evaluation of patients with prolonged disorders of consciousness (DoC) in intensive neurorehabilitation settings. This narrative review critically analyzes the most relevant evidence regarding the use of SEPs and EEG in the management of post-comatose patients, highlighting the strategic role of physiatrists in integrating these assessments into individualized rehabilitation plans. A systematic search was conducted across major international databases (PubMed, Embase, Scopus, Cinahl, and DiTA) until December 2024, selecting consensus documents, official guidelines (including the 2021 ERC/ESICM guidelines), systematic reviews, observational studies, and significant Italian neurophysiological contributions. The literature supports the strong prognostic value of the bilateral presence of the N20 component in SEPs, while its early bilateral absence, particularly in post-anoxic cases, is a robust predictor of poor neurological outcomes. EEG provides complementary information, with continuous, reactive, and symmetrical patterns associated with favorable outcomes, while pathological patterns, such as burst suppression or isoelectric activity, predict a worse prognosis. Combining SEP and EEG assessments significantly improves prognostic sensitivity and specificity, especially in sedated or metabolically compromised patients. Additionally, the use of direct muscle stimulation (DMS) and nerve conduction studies enables accurate differentiation between central and peripheral impairments, which is crucial for effective rehabilitation planning. Overall, SEPs and EEG should be systematically incorporated into the evaluation and follow-up of DoC patients, and the acquisition of neurophysiological competencies by physiatrists represents a strategic priority for modern, effective, and personalized neurorehabilitation. Full article

Background and Objectives: Chronic pain is a significant global health issue, with conventional treatment strategies often proving insufficient or causing undesirable side effects. Interventional pain management techniques, including neuromodulation, have gained increasing interest as alternative therapeutic options. Cryoneurolysis, a technique leveraging extreme cold to modulate pain pathways, has emerged as a promising tool in chronic pain management. However, its efficacy and role within current clinical practice remain under evaluation. Methods: A narrative review was conducted by searching PubMed, Scopus, Embase, and Web of Science databases for studies published between 2010 and 2024 using the keywords “Cryoneurolysis”, “Cryoanalgesia”, “Cryoablation”, and “Chronic pain.” Only English-language studies were included. Studies that examined intraoperative cryoablation or lacked statistical analyses (except case reports) were excluded. Results: A total of 55 studies were included: 4 randomized controlled trials (RCTs), 16 retrospective studies, 4 prospective observational studies, and 31 case reports or small case series. The studies displayed significant heterogeneity in patient selection, targeted nerves, procedural protocols, and follow-up durations. While two RCTs demonstrated a significant pain reduction compared to control groups, other RCTs reported no significant improvement. Observational studies and case reports frequently report positive outcomes, with some achieving complete pain relief. Cryoneurolysis appears to be most effective in treating neuropathic pain, particularly in patients with peripheral nerve involvement. Conclusions: Cryoneurolysis is a safe technique for chronic pain management, which has been successfully applied, particularly for selected neuropathic pain conditions. However, the current evidence is limited by study heterogeneity and a lack of high-quality comparative trials. Further well-designed randomized studies are necessary to define its long-term efficacy and its potential role relative to other interventional pain therapies, such as radiofrequency ablation. Full article

Objectives: This study evaluated peripheral nerve stimulation (PNS) as a treatment for vertebra plana fractures, focusing on its impact on pain intensity, physical function, anxiety, depression, fatigue, social role participation, and pain interference. The goal was to assess whether PNS could serve as a minimally invasive alternative for managing pain in patients with severe vertebral fractures. Methods: Four patients with lumbar vertebra plana fractures received PNS implants for 60 days. Pain scores and PROMIS-29 domains (physical function, anxiety, depression, fatigue, social participation, and pain interference) were assessed at 30, 60, 90, 180, and 365 days post-implantation. Data analysis included mean and standard deviation calculations. Results: PNS led to marked improvements in pain-related outcomes. The average pain intensity scores dropped from 8.5 at baseline to 4.25 at one year, and pain interference scores declined from 61.75 to 54.75. Physical function initially decreased but improved from 38.5 at three months to 46.75 at one year. Changes in depression, anxiety, fatigue, and social participation were minimal, reflecting their multifactorial nature and limited response to pain relief alone. Conclusions: This case series suggests that PNS may significantly reduce pain and pain interference while enhancing physical function in patients with vertebra plana fractures. Its sustained benefits highlight PNS as a promising minimally invasive treatment, especially for those ineligible for traditional procedures. However, the limited improvement in psychological and social domains underscores the need for comprehensive care strategies. Further research is warranted to explore the broader role of PNS in managing vertebral fracture pain. Full article

Background: Hormonal fluctuations during the menstrual cycle (MC) influence pain perception, potentially affecting exercise performance and rehabilitation in women. This effect may be more pronounced in individuals with primary dysmenorrhea (PD), requiring tailored physiotherapeutic and exercise interventions. Objective: To analyze the influence of MC phases on sensory electrical threshold (SET) and pain electrical threshold (PET) in eumenorrheic women with and without PD, considering the potential implications for physical activity and rehabilitation. Methods: An observational longitudinal study was conducted with 34 physically active women, divided into a control group (CG) and a PD group. SET and PET were measured using transcutaneous electrical nerve stimulation (TENS) at the forearm (peripheral site) and lower abdomen (pain-referred site) across five MC phases. Pain intensity was assessed using a Visual Analog Scale (VAS). Results: SET and PET were significantly lower in the premenstrual phase (p < 0.001), suggesting increased pain sensitivity. VAS scores were higher in the PD group during all phases, except for the follicular phase (p < 0.033), with the highest pain levels recorded in the menstrual and premenstrual phases. While no significant differences in SET and PET were found between groups across most phases, the PD group exhibited a significantly higher SET in the forearm during the premenstrual phase (p = 0.005), potentially indicating altered central pain modulation. Conclusions: MC-related hormonal fluctuations affect pain sensitivity, particularly in women with PD. These findings underscore the need for phase-specific exercise adaptations and rehabilitation strategies to improve performance, pain management, and recovery in physically active women. Full article

Background/Objectives: Virtual reality (VR), a component of extended reality (XR), has shown promise in pre-procedural planning by providing immersive, patient-specific simulations. In pain management, where precise anatomical understanding is critical for interventions such as peripheral nerve stimulation (PNS), nerve blocks, and intrathecal pump placement, the application of VR remains underexplored. This case series examines the role of VR in enhancing pre-procedural planning for complex chronic pain interventions. Methods: From August 2022 to December 2024, six patients with anatomically challenging conditions underwent VR-assisted pre-procedural planning at Weill Cornell Medical Center. Patient-specific 3D models were created using the manual or automatic segmentation of imaging data and reviewed in VR to optimize procedural strategies by the surgeons performing the case. Procedures were then performed using conventional fluoroscopic or ultrasound guidance. Results: In all cases, VR facilitated the improved visualization of complex anatomies and informed optimal procedural trajectories. In patients with a complex cancer anatomy, previous surgical changes, or hardware, VR enabled precise PNS lead or needle placement, resulting in significant pain reductions postoperatively. In certain cases where previous interventional pain procedures had failed, VR allowed for a “second opinion” to develop an alternative approach with improved outcomes. Finally, in one case, VR served to potentially prevent patient harm by providing insight to the proceduralists regarding an alternative approach. Across the series, VR enhanced the spatial awareness, procedural accuracy, and confidence in navigating challenging anatomical scenarios. Conclusions: This case series demonstrates the utility of VR in pre-procedural planning for chronic pain interventions. By enabling detailed anatomical visualization and trajectory optimization, VR has the potential to improve outcomes in complex cases. Further studies are needed to evaluate its broader clinical applications and cost-effectiveness in pain management. Full article

Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median nerve with (2) transcranial magnetic stimulation over the primary motor cortex (M1) at different inter-stimulus intervals (25 ms; PAS-25, or 10 ms; PAS-10), corticospinal excitability can be increased (PAS-25, mimicking long-term potentiation (LTP)) or decreased (PAS-10, mimicking long-term depression (LTD)). However, variations in the number of pairings and inter-pair intervals lack consensus. The aim of the study was to evaluate four different PAS paradigms, i.e., PAS-10 and PAS-25 with both 180 versus 225 pairings each, to establish the most reliable PAS protocols for LTP- and LTD-like cortical changes. Methods: In a randomized, double-blind, crossover study, 14 healthy participants underwent PAS-10 and PAS-25 with 180 and 225 pairings. Excitability was assessed by quantifying the EMG response amplitude of a hand muscle to a single stimulus. Results: PAS-25 with 225 pairings produced a robust enhancement of corticospinal excitability, while PAS-25 with 180 pairings was less effective. Surprisingly, PAS-10 with both 180 and 225 pairings also increased excitability. Conclusions: While all four PAS paradigms enhanced M1 excitability, PAS-25 with 225 pairings induced the strongest group-level effects and was most time-efficient. Significant individual variability of PAS responses suggests that optimizing PAS parameters, including pairing number and interstimulus intervals, may be necessary for personalized approaches. Full article