UNASSIGNED: Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial.
UNASSIGNED: In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups.
UNASSIGNED: We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means.
UNASSIGNED: High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain.
UNASSIGNED: https://clinicaltrials.gov/, identifier NCT05488808.

UNASSIGNED: Capsaicin 179 mg (8% weight per weight) cutaneous patch (\"capsaicin patch\") is a recommended topical treatment for peripheral neuropathic pain (PNP). In older patients, topical treatments may be preferred over systemic treatments, but data specific to the older population are scarce.
UNASSIGNED: We conducted pooled analyses of multiple clinical trials to evaluate efficacy and safety of capsaicin patch in older patients. The analysis of efficacy included four randomized, double-blind, 12-week studies with similar trial design comparing a single treatment of capsaicin 179 mg cutaneous patch vs low-dose control patch in post-herpetic neuralgia. For the safety evaluation, data were pooled from 18 interventional studies in which capsaicin patch was used in PNP with varying etiologies.
UNASSIGNED: Capsaicin patch had similar analgesic efficacy in elderly (n=582) and non-elderly patients (n=545) in terms of change from baseline to 2-12 weeks in the 11-point numeric pain rating scale (NPRS) score for average pain over the previous 24 hours. In both age groups, decrease in NPRS score was significantly greater with capsaicin patch vs control. Older patients treated with capsaicin patch were significantly more likely than those in the control group to achieve responder status (ie mean decrease in NPRS score from baseline to week 2-12 of at least 30% or ≥2 points): 36.1% vs 27.1% (odds ratio [OR] [95% CI] 1.52 [1.06, 2.18]; P=0.0231) and 33.1% vs 20.9% (OR [95% CI] 1.90 [1.30, 2.78]; P=0.0009) for active treatment vs control group, respectively. Similar proportions of non-elderly patients (n=2,311) and elderly patients (n=537) treated with capsaicin patch experienced treatment-emergent adverse events (TEAEs) (81.6% and 78.1%, respectively) and serious TEAEs (8.2% and 7.2%), with application-site reactions the most common TEAEs in both groups.
UNASSIGNED: The capsaicin patch was equally efficacious and well tolerated in older patients as in younger patients.
Peripheral neuropathic pain is a common challenge among the elderly, yet effective treatments for this age group remain underexplored. This research focuses on the use of a high-concentration capsaicin patch, a specialized treatment for this type of pain. The patch, which is applied directly to the affected skin area, has been shown to reduce pain significantly for up to 12 weeks. This analysis of multiple clinical trials showed that the high-concentration capsaicin patch significantly reduced pain intensity and was well tolerated in older patients with peripheral neuropathic pain.

BACKGROUND: Peripheral neuropathic pain (NeP), induced by surgical intervention, is a well-known complication or sequela that remains a clinical challenge with few effective treatments. Ideal animal models that can recapitulate surgery-associated NeP remain to be established for both mechanistic studies and drug discovery.
OBJECTIVE: We aimed to establish a new rat model of postsurgical NeP and describe its characteristics, as well as screen-promising therapeutic analgesics.
METHODS: Experimental research in rats.
METHODS: The research took place in the laboratory of Xinqiao Hospital of the Third Military Medical University.
METHODS: To mimic the surgical procedure associated with peripheral nerve injury (PNI), we established a transient compression injury (TCI) in the sciatic nerve. Behavioral tests of nociception were used to confirm the effect and the time course of this pain model. Histological assessments (transmission electron microscopy evaluation and immunohistochemistry) were performed to observe the neuropathological and immunological features. RNA sequencing (RNA-seq) of injured nerves and dorsal root ganglia (DRGs) was conducted to reveal the underlying mechanism in the newly established animal model and screen promising therapeutic targets.
RESULTS: We established a rat model of TCI of the PN and detected nociceptive hypersensitivity of the injured (ipsilateral) nerve by behavioral tests. This animal model of NeP was further confirmed by observing time-dependent changes in mechanical allodynia and thermal hyperalgesia, as well as by examining the activation of microglia in the ipsilateral spinal dorsal horn. Pathophysiologically, TCI induced macroscopic nerve swelling and demyelination, which resulted in inflammatory responses in ipsilateral nerves. We also found inflammatory cell infiltration in the ipsilateral nerve that was sustained for several weeks, which further exacerbated local inflammation and oxidative stress. Moreover, RNA-seq revealed remarkably upregulated inflammatory reactions in PNs and the DRGs. Notably, the overexpression of inflammatory mediators and the infiltration of macrophages and microglia triggered remote immune responses in DRGs. Based on the RNA-seq results, we also confirmed that gabapentin (GBP) exerts therapeutic effects in TCI-induced NeP by regulating alpha2delta-1.
CONCLUSIONS: We did not compare the new rat model with the classical pain model (like chronic constriction injury or spared nerve injury) in histology or transcriptomics.
CONCLUSIONS: We established a new rat model of NeP and thoroughly characterized neuroinflammation in the injured nerve and DRGs. Based on the upregulated genes in DRGs in this model, we screened a promising analgesic (GBP) capable of reducing pain hypersensitivity in surgery-associated NeP.

Neuropathic pain affects about 7-8% of the population, and its management still poses challenges with unmet needs. Over the past decades, researchers have explored the cholinergic system (muscarinic and nicotinic acetylcholine receptors: mAChR and nAChR) and compounds targeting these receptors as potential analgesics for neuropathic pain management. This scoping review aims to provide an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The inclusion criteria were original articles on PNP in rodent models that explored the use of compounds directly targeting cholinergic neurotransmission and reported results of nociceptive behavioral assays. The literature search was performed in the PubMed and Web of Science databases (1 January 2000-22 April 2023). The selection process yielded 82 publications, encompassing 62 compounds. The most studied compounds were agonists of α4β2 nAChR and α7 nAChR, and antagonists of α9/α10 nAChR, along with those increasing acetylcholine and targeting mAChRs. Studies mainly reported antinociceptive effects in traumatic PNP models, and to a lesser extent, chemotherapy-induced neuropathy or diabetic models. These preclinical studies underscore the considerable potential of cholinergic compounds in the management of PNP, warranting the initiation of clinical trials.

OBJECTIVE: Carpal tunnel syndrome (CTS), which is the most common peripheral nerve entrapment syndrome, can commonly persist despite conservative treatment modalities such as wrist splinting or medications. Pulsed radiofrequency represents a minimally invasive pain intervention technique to alleviate pain. The literature was reviewed to establish the effectiveness of PRF therapy for CTS.
METHODS: This is a narrative review of relevant articles on the effectiveness of PRF for CTS.
METHODS: Four databases, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, OVID Emcare, and Web of Science, were systematically searched. 804 records were screened, and the reference lists of eligible articles were examined. For this review, eight extracted studies were narratively explored.
RESULTS: One case report, three retrospective cohorts, one observational prospective study, and three randomized-controlled trials were included. PRF likely provides both an analgesic and functional benefit in patients with mild to severe CTS, and it also shows benefit as an adjunct to carpal tunnel release surgery. Long-term data is limited. It also appears likely that steroid injection may represent a comparable treatment modality to PRF, and there have been positive results when these modalities are used together. Notably, all studies differed in their methodology, making direct comparisons between studies challenging.
CONCLUSIONS: The evidence for PRF in the treatment of CTS, across the range of spectrum of severity or peri-operative to CTS surgery, appears favorable and avoids known side effects of steroid injections. Potential mechanisms for PRF and future directions for research are explored.

Peripheral neuropathic pain (PNP), neuropathic pain that arises from a damage or disease affecting the peripheral nervous system, is associated with an extremely large disease burden, and there is an increasing and urgent need for new therapies for treating this disorder. In this review we have highlighted therapeutic targets that may be translated into disease modifying therapies for PNP associated with peripheral neuropathy. We have also discussed how genetic studies and novel technologies, such as optogenetics, chemogenetics and single-cell RNA-sequencing, have been increasingly successful in revealing novel mechanisms underlying PNP. Additionally, consideration of the role of non-neuronal cells and communication between the skin and sensory afferents is presented to highlight the potential use of drug treatment that could be applied topically, bypassing drug side effects. We conclude by discussing the current difficulties to the development of effective new therapies and, most importantly, how we might improve the translation of targets for peripheral neuropathic pain identified from studies in animal models to the clinic.

Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

UNASSIGNED: Despite effective treatment of leprosy via WHO-approved multi-drug therapy (MDT), patients still suffer from debilitating neuropathic sequelae, including peripheral neuropathic pain (PNP), and continue to develop intercurrent etiologies (such as diabetes), and progressive existing neuropathy over time. Strategies seeking to improve physiological and metabolic wellness, including those that reduce systemic inflammation and enhance immune responsiveness to neurotoxic factors may influence underlying neuropathic etiologies. A whole food plant-based diet (WFPBD) has been shown to be effective in the management of neuropathic pain due to diabetes, limiting severity and relevant symptomology. Diabetes remains a significant sequela of leprosy, as up to 50% of patients in reaction requiring corticosteroids, may develop a biochemical diabetes. As nutritional interventions may modulate both leprosy and diabetes, a specific exploration of these relationships remains relevant.
UNASSIGNED: (1) To demonstrate the effect of a WFPBD lifestyle intervention, on neuropathic pain variables in leprosy; and (2) To contextualize the significance of diet in the treatment of chronic sequelae in leprosy by evaluating tolerability and side effect profile.
UNASSIGNED: A prospective, randomized, controlled, single-blind, multicentre interventional trial is described. Weekly one-hour dietary counseling sessions promoting a WFPBD emphasizing vegetables, fruits, whole-grains, nuts, and legumes, omitting animal products, and limiting fat intake over a six-month duration will be implemented. Participants will be 70 age and sex-matched individuals experiencing active or treated \"cured\" leprosy and PNP, randomized to either intervention or control groups. Primary outcome measures include efficacy via visual analog scale, subjective questionnaire and objective quantitative sensory testing, as well as safety, tolerability, and harms of a WFPBD on PNP in leprosy. This study will be initiated after Research Ethics Board (REB) approval at all participating sites, and in advance of study initiation, the trial will be registered at ClinicalTrials.gov.
UNASSIGNED: It is hypothesized that WFPBDs will mitigate progression and severity of PNP and potentially reduce the adverse events related to standard corticosteroid treatment of leprosy reactions, thereby reducing disease severity. By examining the effects of WFPBDs on PNP in leprosy, we hope to illuminate data that will lead to the enhanced therapeutic management of this neglected tropical disease.

This study aimed to explore the influence of chronic stress, measured through hair cortisol, on executive functions in individuals with chronic pain. We expected that there would be significant differences in chronic stress and executive functioning between pain patients and healthy controls, as well as between primary and secondary pain classifications. We also hypothesized that hair cortisol concentration was predictive of worse performance on tests of executive functions, controlling for objective and subjective covariates. For this study, 122 participants provided a hair sample (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 58 matched healthy controls). Eighty-four of these participants also completed highly detailed testing of executive functions (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 20 healthy controls). To assess differences in stress levels and executive functions, t-tests were used to compare patients with controls as well as fibromyalgia with peripheral neuropathic pain. Then, univariate regressions were used to explore associations between stress and executive functioning in both chronic pain classifications. Any significant univariate associations were carried over to hierarchical multivariate regression models. We found that patients with chronic pain had significantly higher cortisol levels than healthy controls, but all groups showed similar executive functioning. Hierarchical multiple regression analyses disclosed that in a model controlling for age, sex and pain medication usage, hair cortisol levels explained 8% of the variance in spatial working memory strategy in individuals with chronic pain. The overall model explained 24% of the variance in spatial working memory. In a second model using imputed data, including both objective and subjectively reported covariates, hair cortisol levels explained 9% of the variance, and the full model 31% of the variance in spatial working memory performance. Higher levels of cortisol indicated worse performance. In this study, an applied measure of chronic stress, namely hair cortisol, explained a substantial part of the variance on a spatial working memory task. The current results have important implications for understanding and treating cognitive impairments in chronic pain.

UNASSIGNED: Peripheral neuropathy is a neurological disorder characterised by pain, numbness, or tingling due to nerve damage. Peripheral neuropathy is one of the main health issues in Kuwait and is a rising concern which affects a large proportion of the population, therefore the lived experience needs to be explored to identify areas for improvement in care. This qualitative study explored the experiences of people living with peripheral neuropathy in Kuwait.
UNASSIGNED: Semi-structured interviews were conducted with 25 participants recruited from the Neurology Outpatient Clinic of the Ibn Sina Hospital in Kuwait. The interview questions explored their experiences and understanding of pain along with the impact on their daily life. The interviews were audio recorded, transcribed and translated into English then coded using NVivo 12. Thematic analysis was conducted to identify patterns and themes in the data.
UNASSIGNED: Three major themes were identified including treatment beliefs (perceived effectiveness of treatment and seeking alternative treatments), the barriers to pain management (medication side effects, relationships with healthcare professionals and lack of information and access to healthcare), and the impact on quality of life (impact on work and social, physical, and psychological consequences). Self-efficacy was a key construct and over-arching theme that was discussed in all aspects, which finds reflection in the protection motivation theory.
UNASSIGNED: This paper presents the experiences of people living with peripheral neuropathy and highlights there is scope for improvement of current treatments in Kuwait. Self-management strategies are recommended alongside prescribed medication and healthcare professionals are encouraged to use a patient-centered approach. More importantly, information and support on the condition to promote coping strategies and self-efficacy should be adopted to improve quality of life. These findings can be implemented locally and globally to improve the quality of care provided to people living with peripheral neuropathy.