Treatment Of Peripheral Neuropathic Pain Research Articles

Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study

BackgroundFor chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery.MethodsIn this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone.ResultsOf 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were − 51.3 (− 54.9, − 47.7) mm in the mirogabalin add-on group and − 47.7 (− 51.2, − 44.2) mm in the conventional group (between-group difference: − 3.6 [95% CI: − 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P < 0.001). The most common adverse events (AEs) in the mirogabalin add-on group were dizziness (12.7%), somnolence (7.9%), and urticaria (3.2%). Most AEs were mild or moderate in severity.ConclusionsAddition of mirogabalin to conventional therapy did not result in significant improvement in pain intensity based on VAS scores, but did result in significant improvement in ADL and QOL in patients with peripheral NeP after thoracic surgery.Trial registrationJapan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).

Topical capsaicin 8% patch in peripheral neuropathic pain: Efficacy and quality of life.

Peripheral neuropathic pain (PNP) is one of the most challenging diseases to treat with a significant negative impact on the patients' health-related quality of life (HRQoL). Capsaicin 8% patch has arisen in the last decades as an alternative to oral drugs in the treatment of PNP with fewer side effects and promising results in efficacy. This work aims to evaluate the effectiveness of the topical application of capsaicin in PNP and its impact on patients' HRQoL based on the use of capsaicin in a tertiary hospital of Oporto. This study included 100 patients with localized PNP with poor pain control and without improvement with previous treatments that were treated at least once with an 8% capsaicin patch. Effectiveness on pain relief, number of treatments needed, safety and impact on HRQoL were assessed through a set of questionnaires. Regarding the aetiology of PNP, 67.6% (N = 46) have post-surgery or trauma induced PNP with 64.7% (N = 44) of patients reporting pain in the lower limb. After the treatment, 30.9% (N = 21) felt minimally improved, 22.1 (N = 15) felt much improved and 13.2 (N = 9) felt very much improved. On a scale from 1 to 10, in the week prior to the survey, the median intensity of pain was 6 and the median interference in quality of life was 7. The majority of patients still report limitations in mobility and daily activities and moderate pain. Capsaicin 8% patch is effective in PNP treatment at least in the short term. Repeated applications may be important for long-term analgesia. The low systemic dose and few side effects mean that the treatment is generally well tolerated by patients. Due to the analgesic effect, capsaicin can improve the HRQoL of patients with PNP.

The efficacy of a whole foods, plant-based dietary lifestyle intervention for the treatment of peripheral neuropathic pain in leprosy: a randomized control trial protocol.

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. (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. 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. 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.

Mirogabalin - the use of a new gabapentinoid in the treatment of diabetic neuropathy and postherpetic neuropathy and other conditions

Introduction: Mirogabalin is a new drug from the gabapentinoid group first registered in Japan in 2019. It has found use in the treatment of peripheral neuropathic pain in diabetic neuropathy and postherpetic neuropathy. Purpose: In this article, we review studies on the efficacy and safety of mirogabalin in the treatment of registered indications and its potentially new applications. Materials and Methods: We reviewed the literature available in the PubMed database, using the key words: "mirogabalin", "neuropathy" "pregabalin". Results: Mirogabalin has been registered for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuropathy. The literature shows that it is effective and safe in the above-mentioned indications. Its use has also been described: in the treatment of neuropathic pain of other etiologies with intolerance to pregabalin, as a coanalgesic in the treatment of pain in the course of cancer, and in neuropathy caused by chemotherapy. It has been shown to be effective in all of the aforementioned cases. Studies have shown no clinically significant effect of mirogabalin in the symptomatic treatment of fibromyalgia pain. It has a good safety profile and a low number of adverse effects. Conclusions:. Mirogabalin is a drug that has the potential to improve the efficacy of treatment of neuropathic pain due to various causes. There is a need to continue conducting studies on larger groups of patients in order to make wider use of its potential in clinical practice.

Implantable Peripheral Nerve Stimulation for Peripheral Neuropathic Pain: A Systematic Review of Prospective Studies.

Peripheral nerve stimulation (PNS) has been utilized for over 50 years with accumulating evidence of efficacy in a variety of chronic pain conditions. The level and strength of evidence supporting the use of PNS for peripheral neuropathic pain remains unclear. The purpose of this review is to synthesize data from prospective studies on the efficacy of PNS for neuropathic pain as it pertains to pain intensity, neurological deficits/neuropathy (e.g., weakness, sensory deficits, gait/balance), and other secondary outcomes (quality of life, satisfaction, emotional functioning, and adverse events). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this review identified articles from MEDLINE(R), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Overall, per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, pooled results demonstrate very low quality or low quality of evidence supporting modest to substantial improvement in pain and neurological function after PNS implantation for treatment of peripheral neuropathic pain. PNS for phantom limb pain was the only indication that had moderate level evidence. Future prospective and well-powered studies are warranted to assess the efficacy of PNS for peripheral neuropathic pain.

Application of the novel Nalu™ Neurostimulation System for peripheral nerve stimulation.

Peripheral nerve stimulation is an established treatment modality for chronic neuropathic pain. Over the last decade, with the advent of innovative devices and delivery platforms, peripheral nerve stimulation has evolved from invasive open surgeries to image-guided, minimally invasive percutaneous procedures. The authors hereby present a novel device, the Nalu™ Neurostimulation System(Nalu Medical, CA, USA), which has established its advantages in providing predictable and reliable peripheral nerve stimulation therapy for chronic neuropathic pain management. This novel device is effective in treating chronic pain conditions such as post-herniorrhaphy pain syndrome, intercostal neuralgia, post-laminectomy syndrome, and complex regional pain syndromeand holds great promise for the treatment of peripheral neuropathic pain.

A review of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, for the treatment of peripheral neuropathic pain

ABSTRACT Introduction Neuropathic pain (NeP) is a chronic and refractory condition in many patients, and its treatment is a challenge for physicians. A new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, has a high specific binding affinity for the α2δ subunit, with a slower dissociation rate for α2δ-1 than α2δ-2 compared to that of pregabalin. Mirogabalin was shown to be effective in NeP animal models, with a margin of safety between central nervous system side effects and the analgesic effect of the dose. It exerted a favorable analgesic effect, was well tolerated in patients with peripheral NeP (P-NeP), and was first approved in Japan in 2019 and subsequently in Korea and Taiwan in 2020. Areas covered The purpose of this article is to review the pharmacological characteristics, pharmacokinetics, and efficacy and safety of mirogabalin for NeP based on the results of non-clinical and clinical studies. Expert opinion Although there are several first-line therapies for NeP, insufficient efficacy and adverse drug reactions of NeP drugs often cause patient dissatisfaction. Mirogabalin was effective and well tolerated with a step-wise dose increase in clinical studies on P-NeP patients. Thus, mirogabalin is expected to be a useful treatment option for patients with P-NeP.

Pregabalin abuse and dependence in various European countries: Association with substitution policies

Pregabalin was first approved in 2004 for the treatment of peripheral neuropathic pain and focal epileptic seizures, with or without secondary generalization. Prescription frequency has increased significantly since approval. In the early days, little attention was paid to the problem of misuse and dependence on pregabalin; in recent years, there has been a significant increase in the number of publications focusing on this problem. This review deals with these risk factors and risk groups of pregabalin abuse and dependence in different European countries and their drug policies. Pregabalin abuse and dependence has increased significantly since its introduction to the market. It was shown that solo abuse of pregabalin is rare. In most cases, pregabalin was combined with other substances, which is also a predictor of pregabalin abuse. There were different reasons for the non-prescription use of pregabalin; it was used to increase the psychotropic effect, on the one hand, and to alleviate withdrawal symptoms, on the other hand. Furthermore, in Sweden, pregabalin was found in 28% of fatal intoxications among drug addicts. Young people were particularly affected. Abuse of pregabalin was detected in countries with restrictive substitution programmes, while in countries with liberal drug policies, no abuse was detected. However, the data situation in Switzerland with a liberal substitution programme is based on only one study, which is why pregabalin use in liberal substitution programmes cannot be conclusively clarified. There seems to be a connection between a country's drug policy and the illegal use of pregabalin among persons in a substitution programme in that country. There are also risk factors and risk groups for pregabalin dependence and abuse.

Analgesic characteristics of a newly developed α2δ ligand, mirogabalin, on inflammatory pain.

Mirogabalin is a novel α2δ ligand approved in Japan for the treatment of peripheral neuropathic pain. However, the sites of action of α2δ ligands to produce analgesic effects on inflammatory pain remain unclear. In this study, we investigated the analgesic effect and site of action of mirogabalin using the rat formalin test, an acute inflammatory pain model. Mirogabalin was administered orally, intrathecally, and intracerebroventricularly. Open field tests were performed to evaluate the effect of oral-, intrathecally, and intracerebroventricularly administered mirogabalin on locomotor activity and orientation ability. Oral mirogabalin produced an analgesic effect when the formalin test was performed 4 h, but not 1 or 2 h, after oral administration. Intrathecal, but not intracerebroventricular, administration of mirogabalin produced analgesic effects when mirogabalin was administered 10 min before formalin injection. These analgesic effects were not antagonized by idazoxan, an α2 adrenergic antagonist; WAY100135, a 5-HT1A antagonist; or naloxone, an opioid receptor antagonist. Mirogabalin attenuated moving distances 1 and 2 h after oral administration and 10 min after intracerebroventricular administration, but not 10 min after intrathecal administration. In the oral administration group, the time course of the analgesic effect was different from that of moving distance. In the intracerebroventricular group, mirogabalin attenuated moving distances but did not produce an analgesic effect. In the intrathecal group, mirogabalin produced an analgesic effect but did not affect moving distances. These findings suggest that the analgesic effect of mirogabalin on the rat formalin test is mediated by spinal action and not by the activation of α2, 5-HT1A, or opioid receptors, and that the inhibitory effect of mirogabalin on moving distances is mediated by the supraspinal brain.

Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review.

IntroductionPeripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN).MethodsA systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review.ResultsThe best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN.DiscussionResponse to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.Electronic supplementary materialThe online version of this article (10.1007/s40122-020-00210-3) contains supplementary material, which is available to authorized users.

Expert Opinion: Exploring the Effectiveness and Tolerability of Capsaicin 179 mg Cutaneous Patch and Pregabalin in the Treatment of Peripheral Neuropathic Pain.

Background and ObjectiveTreatment of peripheral neuropathic pain (PNP) remains a challenge. In the absence of clear predictors of response, clinical decision-making involves trial and error. While many classes of pharmacological agent are used and have shown efficacy, one of the most commonly used first-line treatments is pregabalin. However, in the 60% of PNP cases in which the pain is localized, a local treatment may be more suitable. This article will summarize the evidence for the relative effectiveness and tolerability of the capsaicin 179 mg patch and pregabalin in the treatment of PNP and highlight the expert opinion of the authors based on their own clinical experiences.ResultsWhen compared in a head-to-head trial in patients with PNP, capsaicin 179 mg patch provided non-inferior pain relief compared with an optimized dose of pregabalin, as well as a reduction in dynamic mechanical allodynia, faster onset of action, fewer systemic side effects, and greater treatment satisfaction. Adverse events associated with capsaicin patch are mainly application site reactions, compared with systemic and central nervous system effects with pregabalin. Studies indicate that capsaicin 179 mg patch is associated with a lower burden of therapy than pregabalin in terms of improved tolerability, lack of a daily pill burden, lack of drug–drug interactions, and increased regimen flexibility.ConclusionIn localized neuropathic pain, evidence supports a pragmatic approach of using a local treatment before considering a systemic treatment. For treatment selection, the patient profile (eg, concomitant medication use, age) and the treatments’ efficacy and tolerability profiles should be considered.

8% Capsaicin Patch in Treatment of Peripheral Neuropathic Pain

Background: Neuropathic pain is a complex condition that is difficult to control and has a high impact on quality of life. 8% Capsaicin patch can be a therapeutic strategy in the treatment of peripheral neuropathic pain. Objectives: This study aims to (1) evaluate clinical efficacy and (2) tolerability of 8% capsaicin patch in a Pain Unit. Study Design: Retrospective observational study Setting: Portuguese Pain Unit Methods: A sample of 120 patients diagnosed with peripheral neuropathic pain, underwent treatment with the 8% capsaicin patch between February 2011 and February 2019 in a Portuguese Pain Unit. Patients were included in one of the following groups according to the etiology of pain: postherpetic neuralgia (PHN), chronic post-surgical pain (CPSP), post traumatic neuropathic pain (PTNP), diabetic neuropathy (DN), regional pain syndrome. complex I and II (CRPS I / II), HIVassociated neuropathy (HIVN), lumbar neuropathic pain (LNP), trigeminal neuralgia (TN) and other neuropathies (O). The evaluated parameters were: pain intensity according to unit protocol (numerical rating scale), pain characteristics, location, size of the painful area. The evolution of pain intensity after treatment (patients were considered as responders to therapy if the decrease in NRS was equal to or greater than 30%; patients with a decrease in NRS of 50% or more were also analyzed), the area of pain and the need for adjuvant analgesic therapy, as well as the tolerability to treatment and the identification of eventual predictors of its efficacy were evaluated, at 15 days, 8 weeks and 12 weeks after 8% capsaicin patch. Results: Of the 120 patients in the sample, 40.8% had a ≥ 30% decrease in basal pain intensity 15 days after treatment, 43.3% after 8 weeks and 45.0% after 12 weeks. 30.8% of patients had ≥ 50% decreased basal pain intensity 15 days after treatment, 27.5% after 8 weeks and 30.0% after 12 weeks. Pain area decreased in 36.7% of patients and 18.3% reduced chronic analgesic therapy within 12 weeks after 8% capsaicin patch application. There was only one case of intolerance to the treatment. Limitations: This study has the limitations inherent to a retrospective study. The study period was only 12 weeks and some diagnostic groups included a small number of patients. Conclusion: Treatment of peripheral neuropathic pain with 8% capsaicin patch seem to be effective in the short and medium term, both in decreasing pain intensity and in reducing the painful area. Its application is tolerated by most patients. Key words: 8% capsaicin patch, peripheral neuropathic pain, pain intensity, painful area

Therapeutic Effect of Mirogabalin on Peripheral Neuropathic Pain due to Lumbar Spine Disease.

Study DesignRetrospective study.PurposeThis study aims to evaluate the effectiveness of mirogabalin in treatment of peripheral neuropathic pain due to lumbar spine disease.Overview of LiteratureMirogabalin is a novel selective ligand for the α2δ subunit of voltage-gated Ca channels.MethodsBetween April and December 2019, we used mirogabalin to treat 60 consecutive patients (mean age, 67.6 years) with leg symptoms due to lumbar disease. The treatment outcome after 8 weeks of mirogabalin therapy was evaluated by comparing the preand post-administration Numerical Rating Scale (NRS) for leg symptoms and sleep disturbance, the NRS and Roland–Morris Disability Questionnaire for low back pain (LBP), and the quality of life (QOL) score (based on EuroQol five-dimension five-level scale).ResultsMirogabalin treatment was stopped at less than eight weeks in eight patients. The remaining 52 patients for evaluation were divided as group 1 (17 patients who presented with leg symptoms that lasted for less than 3 months) and group 2 (35 patients with leg symptoms that lasted longer than 3 months). The leg symptoms and LBP in both groups significantly improved at 4 and 8 weeks of treatment, and sleep disturbance and QOL were improved at 8 weeks as well. Compared to group 2, the pretreatment leg symptoms and QOL were significantly worse in group 1, and their improvement after 8 weeks of mirogabalin treatment was significantly better (p<0.05). Of the 60 original patients, 17 suffered adverse effects, which were mild in 16 patients and required treatment cessation due to excessive weight gain in one patient.ConclusionsWe have validated the effect of mirogabalin on neuropathic pain due to lumbar spine disease, which has effectively addressed the associated leg symptoms, LBP, and sleep disturbance.

Physiotherapy for people with painful peripheral neuropathies: a narrative review of its efficacy and safety.

Pharmacological treatment for peripheral neuropathic pain has only modest effects and is often limited by serious adverse responses. Alternative treatment approaches including physiotherapy management have thus gained interest in the management of people with peripheral neuropathies. This narrative review summarises the current literature on the efficacy and safety of physiotherapy to reduce pain and disability in people with radicular pain and chemotherapy-induced peripheral neuropathy, 2 common peripheral neuropathies. For chemotherapy-induced peripheral neuropathy, the current evidence based on 8 randomised controlled trials suggests that exercise may reduce symptoms in patients with established neuropathy, but there is a lack of evidence for its preventative effect in patients who do not yet have symptoms. For radicular pain, most of the 21 trials investigated interventions targeted at improving motor control or reducing neural mechanosensitivity. The results were equivocal, with some indication that neural tissue management may show some benefits in reducing pain. Adverse events to physiotherapy seemed rare; however, these were not consistently reported across all studies. Although it is encouraging to see that the evidence base for physiotherapy in the treatment of peripheral neuropathic pain is growing steadily, the mixed quality of available studies currently prevents firm treatment recommendations. Based on promising preliminary data, suggestions are made on potential directions to move the field forward.

B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review.

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).

Frequency of Adverse Drug Reactions and Analgesic Effects of Mirogabalin during Treatment of Peripheral Neuropathic Pain: A Retrospective Clinical Investigation.

Introduction Mirogabalin should be equivalent to pregabalin, but with fewer incidences of adverse drug reactions (ADRs). To verify these benefits in actual clinical trials, our study investigated the frequency of ADRs and mirogabalin's analgesic effects during treatment of peripheral neuropathic pain. Methods This study included 74 patients with lower limb pain. We surveyed patient reports of ADRs during the follow-up period as the primary endpoint and examined the visual analog scale (VAS) reported for lower limb pain as the secondary endpoint (before administration, and two and four weeks after administration). Results The occurrence of ADR was 27.0%, like the frequency of ADRs in the clinical trials for other disorders. However, the discontinuation rate of administration was 10.8%, which was significantly lower than the frequency of ADR occurrences. When the analgesic effect was assessed, a significant decrease in the temporal change of VAS for lower limb pain was observed before administration, and two and four weeks after administration. Conclusions In this study, the occurrence of ADRs reported by the patients was like the frequency of ADRs reported in the clinical trials for other disorders. When assessing the analgesic effect, the temporal change of VAS for lower limb pain was found to decrease significantly before administration, and two and four weeks after administration.

Short-term outcomes of mirogabalin in patients with peripheral neuropathic pain: a retrospective study

BackgroundMirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin administration in patients with peripheral neuropathic pain who ceased treatment with pregabalin.MethodsWe retrospectively assessed peripheral neuropathic pain using the neuropathic pain screening questionnaire (NeP score) in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had switched from pregabalin to mirogabalin due to lack of efficacy or adverse events. Differences in the treatment course (i.e., numeric rating scale (NRS) scores) were compared using one-way analysis of variance with Bonferroni post hoc tests.ResultsThe mean age of the patients was 72.3 years (range, 30–94 years), and the mean duration of disease was 37 months (range, 3–252 months). After treatment with mirogabalin for 1 week, NRS scores significantly decreased compared with baseline and continued to decrease over time. After 8 weeks, NRS scores improved by ≥ 30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin.ConclusionsThe results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain.

Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A Systematic Review

Repetitive magnetic stimulation (rMS) is a safe and well-tolerated intervention. Transcranial magnetic stimulation (TMS) is used for the treatment of depression and for the treatment and prevention of migraine. Over the last few years, several reports and randomised controlled studies of the use of rMS for the treatment of pain have been published. The aim of this systematic review was to identify the available literature regarding the use of rMS in the treatment of peripheral neuropathic pain. After a systematic Medline search we identified 12 papers eligible to be included in this review. The majority of the studies were on patients with phantom limb pain, followed by radiculopathy, plexopathy, post-traumatic pain and peripheral neuropathy. The treatment protocols vary significantly from study to study and, therefore, pooling the results together is currently difficult. However, rMS has a definite immediate effect in pain relief which, in the majority of studies, is maintained for a few weeks. rMS seems to be a promising intervention in the treatment of peripheral neuropathic pain. Further research is in the field is needed. Use of neuronavigation might increase the precision of stimulation and subsequently its effectiveness.

Capsaicin 8% dermal patch in peripheral neuropathic pain: a profile of its use

A dermal patch containing a high (8%) capsaicin concentration (hereafter referred to as the capsaicin 8% dermal patch) [Qutenza®] is a useful option for the treatment of peripheral neuropathic pain (PNP). The patch, referred to as Qutenza 179 mg cutaneous patch in the EU summary of product characteristics, is indicated in the EU for the treatment of PNP in adults, either alone or in combination with other medicinal products for pain. Prolonged exposure to capsaicin (the main pungent component in hot chilli peppers) appears to engender analgesia/pain relief by inducing cutaneous nociceptor ‘defunctionalisation’ [i.e. a cascade of events, including a reduction in TRPV1 (transient receptor potential vanilloid-1) receptor sensitivity to various painful or noxious stimuli, resulting in impaired local nociceptor function for an extended period]. Across clinical and real-world studies in patients with painful diabetic peripheral neuropathy (PDPN) or non-diabetic PNP, including post-herpetic neuralgia (PHN) and HIV-associated neuropathy, single applications of the capsaicin 8% dermal patch generally relieved pain and improved health-related quality of life, patient status and/or treatment satisfaction. Pain relief was at least sustained following repeated applications for ≤ 52 weeks. As the capsaicin 8% dermal patch is associated with minimal systemic absorption, its use is expected to result in few systemic adverse events or drug–drug interactions.

Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury.

Central neuropathic pain develops in greater than 75% of individuals suffering a spinal cord injury (SCI). Increasingly, sex is recognized as an important biological variable in the development and treatment of peripheral neuropathic pain, but much less is known about the role of sex in central neuropathic pain and its pharmacological inhibition. To test the hypothesis that efficacy of analgesic therapies differs between males and females in SCI, we used a mouse model of SCI pain to determine the analgesic efficacy of pioglitazone (PIO), U.S. Food and Drug Administration–approved drug for the treatment of diabetes, and azithromycin (AZM), a commonly prescribed macrolide antibiotic with immunomodulatory properties. Male and female mice received moderate-severe T9 contusion SCI (75-kdyn). A robust heat hyperalgesia developed similarly between male and female mice by 4 weeks post-injury and lasted throughout the duration of the study (14 weeks). Three months after SCI, mice were treated with PIO (10 mg/kg, intraperitoneal) or AZM (160 mg/kg, oral). We observed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males. In contrast, AZM was effective in both sexes. Our data support the use of PIO and AZM as novel therapies for SCI pain and highlight the importance of considering sex as a biological variable in clinical and experimental SCI pain research.