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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.
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OBJECTIVE@#To investigate the effect of escin in relieving chemotherapy-induced peripheral neuropathic pain in rats and explore and the underlying mechanism.@*METHODS@#Eighteen SD rats were randomly divided into 3 groups (@*RESULTS@#The rats in both the escin preconditioning group and escin postconditioning group showed obviously increased thresholds of mechanical allodynia and thermal hyperalgesia as compared with those in the control group (@*CONCLUSIONS@#Escin can alleviate chemotherapy-induced peripheral neuropathic pain in rats possibly by upregulating the expressions of autophagy-related proteins in the spinal cord.
Subject(s)
Animals , Mice , Rats , Antineoplastic Agents/therapeutic use , Autophagy , Escin/therapeutic use , Hyperalgesia/drug therapy , Neuralgia/drug therapy , Rats, Sprague-Dawley , Spinal CordABSTRACT
Resumen El dolor neuropático es una entidad que provoca discapacidad al paciente y su diagnóstico y tratamiento es un reto para los médicos. En un porcentaje importante de pacientes afectados, el dolor neuropático se presenta circunscrito a un dermatoma o a una región concreta del cuerpo, denominándose en ese caso dolor neuropático localizado. No existen guías clínicas mexicanas que postulen recomendaciones para el diagnóstico y tratamiento del dolor neuropático localizado en nuestra población. En este artículo se exponen las recomendaciones de un consenso multidisciplinario realizado con especialistas de distintas áreas implicadas en el diagnóstico y tratamiento de este tipo de pacientes.
Abstract Neuropathic pain is an entity that causes patient disability and its diagnosis and treatment is a challenge for physicians. In a significant percentage of patients with neuropathic pain, it is restricted to one dermatome or to a particular region of the body; in this case, it is referred to as localized neuropathic pain. There are no Mexican clinical guidelines proposing recommendations for the diagnosis and treatment of localized neuropathic pain in our population. This article presents the recommendations of a multidisciplinary consensus of specialists from different areas involved in the diagnosis and treatment of this type of patients.
Subject(s)
Humans , Peripheral Nervous System Diseases/diagnosis , Neuralgia/diagnosis , Peripheral Nervous System Diseases/therapy , Mexico , Neuralgia/therapyABSTRACT
Introduction: Diabetes mellitus frequently leads to development of peripheral neuropathies in almost 30-50% of patients and the most common type of neuropathy associated with this condition is Distal Symmetric Sensorimotor Polyneuropathy (DSPN). Gabapentin and Amitriptyline are two drugs frequently used for the treatment of neuropathic pain associated with type 2 diabetes. Aim of the study: The aim of this study was to compare efficacy and safety of Gabapentin and Amitriptyline in subjects of Type 2 diabetes mellitus with peripheral neuropathic pain. Material and Methods: A prospective, open, randomized, parallel group, comparative study was conducted in 60 patients coming to Department of Medicine, Rajindra Hospital attached to Government Medical College Patiala, to evaluate the efficacy and safety of Gabapentin and Amitriptyline in patients with diabetic peripheral neuropathic pain. The patients fulfilling the inclusion criteria were included in the study after taking written informed consent. The patients were divided into two groups of 30 cases each by simple randomization. Group I patients received Gabapentin 300 mg HS by oral route. Group II patients received Amitriptyline 25 mg HS by oral route. Therapeutic efficacy of both drugs, by using Michigan Neuropathy Screening Instrument (MNSI) was compared at the baseline and at the end of 4 months. Any adverse drug reactions of the respective drug observed in patient were also noted. All the observations thus made were statistically analysed using appropriate tests. Results: Baseline characteristics of the patients in two groups such as age, sex, duration of diabetes were similar (p>0.05). The mean age in group I and group II were 53.40±8.41 years and 57.17±8.55 years, respectively. There was statistically significant reduction in mean MNSI scores in questionnaire part and physical examination part in both the groups. Also, there was statistically significant difference between the two drugs in reducing mean MNSI score. Mean difference between two drugs in reducing MNSI score in history part (0.77±0.16, p<0.01) and physical examination part (0.75±0.19, p<0.01) favoured Gabapentin. No. of adverse drug reactions reported were significantly higher in Amitriptyline group, p value (<0.05) for the difference in ADRs between two drugs was statistically significant. Conclusion: In this study, we concluded that both drugs lead to improvement in signs and symptoms of diabetic neuropathy. Gabapentin was proved to be more efficacious than Amitriptyline. Gabapentin treated patient’s mean MNSI score at the study end point was significantly lower as compared to the Amitriptyline treated patient’s end-point score. Adverse drug reactions reported in our study were mild in both the groups and a significantly higher number of adverse effects were reported in the amitriptyline group. Dizziness and somnolence were two most commonly reported adverse drug reactions.
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OBJECTIVE: To compare the effects and safety of pregabalin for the treatment of diabetic peripheral neuropathic pain. METHODS: Cochrane library, MEDLINE, Embase, PUBMED, CNKI, VIP database, Wan fang database and paper manual of related conferences were searched. The Meta-analysis was performed by RevMan 5. 1. RESULTS: Eight studies were included (n = 1596). The analysis indicated that there were significant differences between pregabalin and placebo in respondent rate[OR = 2.81, 95%CI(2.03, 3.89), P < 0.00001], endpoint mean pain scores [WMD = - 1.08, 95% CI(- 1.52, - 0.63), P < 0.00001], patient global impression of change[OR = 2.94, 95% CI(2.05, 4.20), P < 0.00001] and clinical global impression of change[OR = 2.42, 95%CI(1.53, 3.82), P = 0.0001]. The subgroup analysis showed that the efficacy treated with 600 mg·d-1 is superior to that with 300 mg·d-1. The adverse event rate is higher treated with pregabalin than that with placebo [OR = 5.71, 95%CI(4.05, 6.60), P < 0.00001]. Compared with 5% lidocaine(Lignocaine) medicated plaster, the efficacy of pregabalin is similar while adverse event rate is higher. There were similar efficacy and safety between pregabalin and duloxetine. CONCLUSION: With superior effects, similar safety, pregabalin may be preferred for the patients with diabetic peripheral neuropathic pain.
ABSTRACT
Con la introducción y el desarrollo de nuevos productos que han demostrado ser eficaces en el dolor neuropático (DN), se ha generado una clara necesidad de tener un algoritmo basado en la evidencia para tratar las diferentes condiciones del DN. El objetivo de este artículo es elaborar unas recomendaciones para el tratamiento del DN que estén avaladas por la evidencia científica y que estén consensuadas por un grupo multidisciplinario de expertos en metodología y en tratamiento del dolor. La evidencia se ha obtenido de estudios de metanálisis que recogen la mayor información disponible para cada tipo de DN. La búsqueda bibliográfica se llevó a cabo por 5 revisores, que se centraron individualmente en las diferentes formas de presentación del DN. Las bases de datos consultadas fueron la Cochrane Library, EMBASE (año 2000 en adelante) y PUBMED(año 2000 en adelante), y se seleccionaron metaanálisis y ensayos clínicos aleatorizados y controlados. Finalmente, los autores, especialistas en dolor, evaluaron e hicieron las recomendaciones clínicas para el tratamiento del DN. En algunos tipos de DN, de los cuales no hay suficiente información, se han incluido recomendaciones basadas en publicaciones científicas sin evidencia, con el objetivo de que estas recomendaciones proporcionen la mayor información posible acerca de su tratamiento. Se han revisado estudios de eficacia y seguridad de neuralgia postherpética (NPH), neuropatía diabética dolorosa (NDD) y neuralgia del trigémino(NT) como paradigmas de DN periférico, y también se ha recogido la escasa información existente acerca del DN central(DNC) y el dolor simpático (DS). Con los resultados obtenidos con este estudio bibliográfico y las evidencias extraídas, se ha elaborado un algoritmo de decisión con los fármacos disponibles actualmente en la farmacopea española para la NPH y la NDD; por otro lado, y de forma independiente, para la NT y, finalmente, para el DNC y el DS.
The introduction and development of new products with demonstrated efficacy in neuropathic pain has generated a clear need for an evidence-based algorithm to treat the different types of neuropathic pain. The present article aims to provide recommendations on the treatment of neuropathic pain supported by the scientific evidence and agreed on by consensus by a multidisciplinary group of experts in methodology and pain management. The evidence was obtained from meta-analyses including the greatest amount of information available for each type of neuropathic pain. The literature search was performed by 5 reviewers, who focussed individually on the distinct forms of presentation of neuropathic pain. The databases consulted were the Cochrane Library, EMBASE (from 2000 onwards), and PUBMED (from 2000 onwards). Meta-analyses and randomized, controlled clinical trials were selected. Finally, retrieved articles were evaluated and clinical recommendations for the treatment of neuropathic pain were designed by the pain specialists. For some types of neuropathic pain, there is insufficient information. In these types of pain, recommendations based on scientific publications without evidence were included to provide the reatest possible amount of information on their treatment. Studies of safety and efficacy in postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia (TN) were reviewed as paradigms of peripheral neuropathic pain. The scarce available information on central neuropathic pain (CNP) and sympathetic pain (SP) was also gathered. Based on the results obtained with this literature review and the evidence extracted, a decision algorithm was designed with the drugs currently available in the Spanish pharmacopeia for PHN and PDN, and separate decision algorithms were designed for TN and finally for CNP and S P.
Subject(s)
Humans , Analgesics/therapeutic use , Anesthetics/therapeutic use , Neuralgia/drug therapy , Algorithms , Neuralgia, Postherpetic/drug therapy , Trigeminal Neuralgia/drug therapy , Diabetic Neuropathies/drug therapyABSTRACT
Thermography shows skin temperature changes in various conditions of body. Skin temperature changes according to the subcutaneous blood flow which is regulated by the autonomic nervous system. Peripheral neuropathic pain can be influenced by the sympathetic activities which also can change the skin temperature of affected sites. To evaluate the usefulness of thermography in the detection of peripheral neuropathic pain, authors analyzed thermographic images of 47 cases with peripheral nerve injuries of upper extremities. The peripheral nerve injuries were confirmed by Electromyographic studies in all of the cases. The peripheral neuropathic pain was present in twenty three cases. The results show that 97.5% of nerve injury patients with pain and 45.8% of nerve injury patients without pain had abnormal thermograms with a mean temperature changes of delta T=0.99oC deltaT=0.13oC respectively. Authors conclude that thermography can be an usefal tool for the detection of peripheral neuropathic pain.