Search Results (1,355)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Objective: This study aimed to improve the understanding of the lives of patients with chronic neuropathic pain planned for invasive motor cortex stimulation (iMCS) and assess their expectations towards this intervention and its impact. Methods: Semi-structured face-to-face interviews were conducted until saturation of data was reached. Patients were recruited from one university medical center in the Netherlands. All interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis using iterative and inductive coding by two researchers independently. Results: Fifteen patients were included (11 females; mean age 63 ± 9.4 yrs). Analysis of the coded interviews revealed seven themes: (1) the consequences of living with chronic neuropathic pain; (2) loss of autonomy and performing usual activities; (3) balancing energy and mood; (4) intimacy; (5) feeling understood and accepted; (6) meaning of life; and (7) the expectations of iMCS treatment. Conclusions: This is the first qualitative study that describes the suffering of patients with chronic neuropathic pain, and their expectations prior to invasive brain stimulation. Significant themes in the lives of patients with chronic pain have been brought to light. The findings strengthen communication between physicians, caregivers, and patients. Practice Implications: The insights gathered from the interviews create a structured framework for comprehending the values and expectations of patients living with central pain and reveal the impact of symptoms due to the central pain. This knowledge improves the communication between physicians and caregivers on one side and the patient on the other side. Furthermore, the framework enhances the capacity for shared decision-making, particularly in managing expectations related to iMCS. Full article

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

The use of Botulinum Neurotoxin A (BoNT/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting effects and safety. This study examined the effects of IncobotulinumtoxinA (Inco/A), a BoNT/A variant without accessory proteins, on nerve regeneration in rats using the chronic constriction injury (CCI) model. Inco/A was administered perineurally at two time points: on days 0 and 21 post CCI. Functional and histological assessments were conducted to evaluate the effect of Inco/A on nerve regeneration. Sciatic Functional Index (SFI) measurements and Compound Muscle Action Potential (CMAP) recordings were conducted at different time points following CCI. Inco/A-treated animals exhibited a 65% improved SFI and 22% reduction in CMAP onset latencies compared to the vehicle-treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco/A-treated animals and 60% reduction in CGRP and double S100β signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco/A treatment, suggesting that its anti-inflammatory effect contributes to nerve regeneration. These findings show that two injections of Inco/A promote functional recovery by enhancing neuroregeneration and modulating inflammatory processes, supporting the hypothesis that Inco/A has a neuroprotective and restorative role in nerve injury conditions. 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

Background: Post-traumatic trigeminal neuropathic pain (PTTNP) is a chronic condition often caused by dental procedures such as implant placement or tooth extraction. It involves persistent pain and sensory disturbances, negatively affecting the quality of life of patients. Methods: This retrospective observational study was conducted at Chosun University Dental Hospital and included 120 patients diagnosed with PTTNP involving the orofacial region. Patient data were collected between January 2014 and December 2023. Among them, 79 patients (65.8%) developed PTTNP following dental implant placement, with a total of 121 implants analyzed. The inferior alveolar nerve was most frequently involved. Clinical factors, including the time to treatment, removal of the causative factor, the Sunderland injury grade, and the type of treatment, were evaluated. Pain intensity and sensory changes were assessed using the visual analog scale (VAS). Results: Treatment initiated within the early post-injury period, commonly regarded as within three months, and implant removal tended to improve outcomes. Pharmacological therapy was the most commonly employed modality, particularly gabapentinoids (e.g., gabapentin, pregabalin) and tricyclic antidepressants such as amitriptyline. However, combined therapy, which included pharmacologic, physical, and surgical approaches, was associated with the greatest sensory improvement. Conclusions: Prompt, multidisciplinary intervention may enhance recovery in patients with PTTNP. Implant-related injuries require careful management, and multimodal strategies appear more effective than monotherapies. Full article

Disruption of circadian rhythms by abnormal light exposure and reduced melatonin secretion has been linked to heightened pain sensitivity and opioid tolerance. This study evaluated how environmental light manipulation and exogenous melatonin supplementation influence pain perception and morphine tolerance in a rat model of neuropathic pain induced by partial sciatic nerve transection (PSNT). Rats were exposed to constant darkness, constant light, or a 12 h/12 h light–dark cycle for one week before PSNT surgery. Behavioral assays and continuous intrathecal (i.t.) infusion of morphine, melatonin, or their combination were conducted over a 7-day period beginning immediately after PSNT. On Day 7, after discontinued drugs infusion, an acute intrathecal morphine challenge (15 µg, i.t.) was administered to assess tolerance expression. Constant light suppressed melatonin levels, exacerbated pain behaviors, and accelerated morphine tolerance. In contrast, circadian-aligned lighting preserved melatonin rhythms and mitigated these effects. Melatonin co-infusion attenuated morphine tolerance and enhanced morphine analgesia. Reduced pro-inflammatory cytokine expression and increase anti-inflammatory cytokine IL-10 level and suppressed astrocyte activation were also observed by melatonin co-infusion during morphine tolerance induction. These findings highlight the potential of melatonin and circadian regulation in improving opioid efficacy and reduced morphine tolerance in managing neuropathic pain. Full article

Chronic postsurgical or posttraumatic pain (CPSP) is a persistent pain condition lasting beyond three months after tissue injury, often associated with neuropathic features and pathological angiogenesis. This study investigated the feasibility, safety, and therapeutic potential of transarterial embolization (TAE) in patients with CPSP arising from prior musculoskeletal surgeries or interventions. Six patients with refractory pain and imaging evidence of abnormal neovascularization were retrospectively reviewed. TAE was performed using imipenem/cilastatin particles to selectively target pathological vasculature. Eleven procedures were conducted, achieving 100% technical and clinical success. Mean Numeric Rating Scale scores improved significantly from 7.8 at baseline to 1.3 at final follow-up (p < 0.001). No major adverse events occurred, and follow-up imaging demonstrated resolution of inflammation in selected cases. These results support the role of TAE as a minimally invasive treatment option for intervention-related CPSP involving the musculoskeletal system, and further prospective studies are warranted. Full article

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Complex regional pain syndrome (CRPS) is a disabling pain condition, which is distinct from other pain syndromes by the presence of autonomic dysfunction and regional inflammatory changes. Objectives: To explore the impact of pharmacological treatment strategies, specifically scheduled, on-demand dosing regimens versus lack of medical treatment, on pain-related and functional outcomes in rehabilitation for individuals with CRPS. Methods: A total of 32 participants with CRPS were assigned to three treatment groups depending on analgesic treatment during the course of complex rehabilitation. Pre- and post-rehabilitation assessments were conducted using validated measures, including the Numerical Rating Scale (NRS) for pain, the Short-Form McGill Pain Questionnaire (SF-MPQ), PainDETECT, the Disabilities of the Arm, Shoulder, and Hand (DASH), and the Lower Extremity Functional Scale (LEFS). Results: Significant improvements in pain and upper limb function (DASH scores) were observed across all groups (p < 0.05). No statistically significant changes were found in lower limb function (LEFS). Between-group comparisons revealed significant differences in post-treatment pain scores (SFMPQ-B), particularly between groups with a constant treatment regimen and those without treatment. Conclusions: There were no statistically significant changes compared to different treatment regimen groups. The constant treatment group showed slightly better average improvements in pain and disability compared to other groups. Statistically significant improvements in all CRPS patients were observed in pain-related and functional measures. Full article

Background/Objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI). Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA. Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups. Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation. Full article

Objectives: Burning mouth syndrome (BMS) is a chronic, painful, idiopathic condition of the oral cavity, characterized by the absence of visible pathological changes on the oral mucosa and normal laboratory findings. Recent evidence from the literature supports the classification of BMS as a neuropathic condition. It has been proposed that oxidative stress may contribute to neuropathic pain. N-acetylcysteine (NAC) is an antioxidant that exhibits neuroprotective properties. The aim of the study was to evaluate the efficacy of N-acetyl cysteine in the treatment of burning mouth syndrome (BMS). Methods: Eighty female patients with previously diagnosed BMS were randomly assigned to one out of two groups. One group received N-acetyl cysteine (600 mg/twice a day) and the other received placebo, for an eight-week period. The outcome was measured by the Oral Health Impact Profile-14 (OHIP-14) quality of life questionnaire and Numeric Pain Rating Scale, for burning and discomfort, both before and after completing the therapy. Results: Both groups experienced a significant reduction in burning and discomfort sensations, along with a significant improvement in oral health-related quality of life. However, the difference between the treatment and control group was not statistically significant. Conclusions: NAC does not significantly improve the oral health-related quality of life, burning sensations, and discomfort in BMS subjects compared to placebo. 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

Neuropathic pain (NP) is a prevalent clinical condition resulting from diseases or injuries affecting the somatosensory system. Conventional analgesics often exhibit limited efficacy, leading to suboptimal therapeutic outcomes. The pathogenesis of NP is complex and involves multiple mechanisms. The existing evidence suggests that maladaptive neuronal plasticity plays a central role in NP development. Additionally, emerging research highlights the contribution of neuroinflammatory responses mediated by glial cells in the onset of NP and associated sensory hypersensitivity. Among non-invasive neuromodulation techniques, transcranial direct current stimulation (tDCS) has gained prominence as a potential treatment for NP. Numerous studies have demonstrated its analgesic effects; however, the precise regulatory mechanisms remain unclear. The current evidence indicates that tDCS may alleviate NP by enhancing glial–neuronal interactions, which suppress nociceptive signaling pathways and reduce pain sensitivity. The reciprocal modulation between tDCS-mediated anti-inflammatory actions, as evidenced by decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators, and its facilitation of adaptive neural plasticity represents a particularly compelling therapeutic axis. This review elucidates inflammatory regulation by tDCS as a fundamental mechanism for NP alleviation, while delineating important unresolved questions regarding these complex interactions. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article