治疗神经病理性疼痛新药：mirogabalin

mirogabalin是一种新型的钙离子通道调节剂,于2019年在日本获批上市用于治疗神经病理性疼痛。与普瑞巴林相比,mirogabalin可通过选择性结合电压依赖性钙离子通道α₂δ-1亚单位,表现出更加长效良好的镇痛作用。多项临床试验验证了mirogabalin治疗神经病理性疼痛安全、有效,不良反应较少,患者耐受良好。     

静脉注射免疫球蛋白对神经病理性疼痛治疗作用的研究进展

静脉注射免疫球蛋白具有多种免疫调节方面的功能,临床上常用于自身免疫性疾病的治疗。近年来,静脉注射免疫球蛋白也应用于许多神经系统疾病的治疗,因为部分神经系统疾病的发病机制与免疫调节相关。神经病理性疼痛是慢性顽固性的疼痛综合征,发病机制复杂,免疫调节也参与神经病理性疼痛的发生。目前发现静脉注射免疫球蛋白可以明显减轻神经病理性疼痛患者的疼痛,给药后无严重不良反应的发生,而且在镇痛的同时可以促进伤口的愈合,提高患者的生活质量。其作用机制可能是免疫球蛋白可以阻断自身抗体与Fc受体结合或中和自身抗体,减轻补体介导的组织损伤作用;还可以通过降低炎性细胞因子表达减轻患者的疼痛。     

癌性神经病理性疼痛概述

1定义及分类临床上疼痛是一种常见的自觉症状,是机体的一种自我保护反应,任何形式的刺激,只要超过痛阈即可引起疼痛。疼痛的表现形式多样,患者在躯体和心理上遭受极大的痛苦,严重影响生活质量。     

普瑞巴林治疗神经病理性疼痛临床分析

神经病理性疼痛是指周围和(或)中枢神经系统、原发和(或)继发性损害、功能障碍或短暂性紊乱所引起的疼痛[1].神经病理性疼痛患者疼痛剧烈,病程较长,严重影响患者的生活质量.临床上多应用抗抑郁、抗癫痫及阿片类镇痛药,疗效不佳,不良反应较大.普瑞巴林对神经病理性疼痛具有良好疗效且安全性较好,报告如下.     

普瑞巴林治疗神经病理性疼痛的Meta分析

目的对普瑞巴林治疗神经病理性疼痛的有效性和安全性进行评价。方法计算机检索PubMed、The Cochrane Clinical Trials Register、Elsevier、Springer Link、OVID、John Wiley、Google Scholar、中国期刊全文数据库(CNKI)、万方数据知识平台,检索起始时间为从建库开始至2013年8月。收集关于普瑞巴林治疗神经病理性疼痛的随机对照试验。以疼痛强度、疼痛对睡眠影响的程度、不良事件发生例数为评价指标。用Rev Man 5.1软件进行数据分析。结果共纳入12项RCTs(共2 408人),研究质量均为A级或B级。与安慰剂组相比,普瑞巴林组疼痛度、疼痛对睡眠影响的程度均显著降低([SMD=-1.06,95%CI(-1.38,-0.73),P<0.000 01],[SMD=-1.35,95%CI(-1.39,-1.31),P<0.000 01]),但不良事件显著增加([OR=4,95%CI(2.08,7.68),P<0.000 01])。嗜睡、眩晕、口干、水肿等是普瑞巴林常见不良反应,一般为轻到中度。结论普瑞巴林治疗神经病理性疼痛的有效性和安全性较好。     

抗癫痫药物治疗神经病理性疼痛的对照研究

目的：探讨不同抗癫痫药物治疗神经病理性疼痛的临床效果。方法80例神经病理性疼痛患者,将患者按照治疗时间分为实验组和对照组,每组40例。对照组采用卡马西平治疗,实验组口服加巴喷丁治疗,比较两组临床效果。结果本次调研中,患者用药后第1天,实验组有29例轻度疼痛,7例中度疼痛,4例重度疼痛;用药后第2天,实验组有33例轻度疼痛,5例中度疼痛,2例重度疼痛;患者用药第3天后,实验组36例轻度疼痛,3例中度疼痛,1例重度疼痛,均优于对照组（P〈0.05）。结果加巴喷丁和卡马西平临床止痛效果较好,但是加巴喷丁并发症较少,值得推广使用。     

周围神经卡压性病理性疼痛的研究进展

神经病理性疼痛是神经系统损伤引起的一种慢性疼痛,其机制涉及异位放电、交感一感觉耦联、解剖重构、脊髓背角神经元的敏感化、中枢抑制性神经元功能下降、高位中枢的敏感化等。药物治疗仍然是目前主要的治疗方法。虽然各种治疗已经在动物试验中取得了许多进展,但是距离临床应用还是有很大的距离。本文就神经病理性疼痛的机制和治疗的进展进行综述,旨在为神经病理性疼痛临床治疗提供参考。     

加巴喷丁治疗神经病理性疼痛的理论与临床应用

加巴喷丁(Gabapentin，又名Keurontin)是近年来广泛应用于治疗癫痫的药物，亦是当前国外临床应用与研究的热点课题。国内对此药的认识刚刚起步，而且被定为抗癫痫类药物．实际上它是属于一种治疗神经病理性疼痛的镇痛药。国内已有文章介绍。加巴喷丁于1993年首先在英国上市用于治疗癫痫大发作，同年美国FDA批准其临床应用。     

氯胺酮对神经病理性疼痛大鼠行为学及坐骨神经的影响

目的 探讨氯胺酮对神经病理性疼痛(NP)大鼠行为学和坐骨神经的影响.方法 24只SD大鼠随机均分为假手术组(S组)、坐骨神经慢性压迫性损伤(CCI)模型组(NP组)和CCI模型+氯胺酮处理组(NPK组).S组大鼠仅分离坐骨神经;NP组和NPK组建立CCI模型.S组和NP组分别于术后7～14 d每天腹腔注射生理盐水10 ...     

加巴喷丁与阿米替林联合治疗神经病理性疼痛

目的采用加巴喷丁联合阿米替林治疗神经病理性疼痛,观察其疗效及安全性。方法 72例神经病理性疼痛患者给予加巴喷丁及阿米替林治疗4周,采用VAS评分评估患者疗效,并观察不良反应。结果加巴喷丁及阿米替林治疗后VAS评分明显下降,P〈0.05。对各组神经病理性疼痛的治愈率均在65%以上,同时严重不良反应发生率低（为2.8%）。结论加巴喷丁联合阿米替林治疗神经病理性疼痛安全有效。     

Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models

1. Although cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central cannabinoid CB(1) receptor-mediated motor and psychotropic side-effects. The actions of endocannabinoids, such as anandamide, are terminated by uptake and subsequent intracellular enzymatic degradation. In the present study, we examined the effect of acute administration of the anandamide transport inhibitor AM404 in rat models of chronic neuropathic and inflammatory pain. 2. Systemic administration of AM404 (10 mg/kg) reduced mechanical allodynia in the partial sciatic nerve ligation (PNL) model of neuropathic pain, but not in the complete Freund's adjuvant (CFA) model of inflammatory pain. 3. The effect of AM404 in the PNL model was abolished by coapplication with the selective cannabinoid CB(1) receptor antagonist AM251 (1 mg/kg). AM404 did not produce a reduction in motor performance in either the PNL or CFA models. 4. These findings suggest that acute administration of AM404 reduces allodynia in a neuropathic pain model via cannabinoid CB(1) receptor activation, without causing the undesirable motor disruption associated with cannabinoid receptor agonists.     

Therapeutic potential of matrix metalloprotease inhibitors in neuropathic pain

Importance of the field: Millions of people suffer from neuropathic pain (NP), but the treatment is empirical and results in transient relief in only a few patients. This is primarily because of the poor understanding of the molecular mechanism underlying NP. Following nerve injury, there is a differential and temporal pattern of MMPs expression that coincides with changes in levels of pro-inflammatory cytokines, suggesting that MMPs not only act as mediators for neuroinflammation but might also be directly involved in pain associated with nerve damage.

Areas covered in this review: The present review describes the different mechanisms of NP. The main focus of the review is to highlight the importance of MMPs in NP and their inhibition as a novel approach for treating NP.

What the reader will gain: A comprehensive overview of the role of MMPs in the pathogenesis of NP and the potential of MMP inhibition as a therapeutic intervention for NP.

Take home message: Targeted therapy using specific MMP inhibitors, siRNAs, peptide inhibitors and monoclonal antibodies can provide a better way of treatment by blocking a single MMP and can reduce the side effects of broad-spectrum MMP inhibitors.     

Zucapsaicin for the treatment of neuropathic pain

Introduction: Neuropathic pain (NP) is a chronic disease that stems from a primary lesion or dysfunction of the central or peripheral nervous system. Zucapsaicin is a synthetic cis isomer of natural capsaicin that has shown therapeutic efficacy in pain accompanying osteoarthritis of the knee. It is also currently under investigation for the relief of severe pain in adults suffering from NP.

Areas covered: The authors provide an overview of the pharmacological properties of zucapsaicin based on available data from both preclinical and clinical trials. They also discuss its mechanism of action.

Expert opinion: The mechanism of action and clinical indications of zucapsaicin are similar to that of its naturally occurring isomer, capsaicin. However, in contrast to capsaicin, zucapsaicin is better tolerated. In the future, zucapsaicin could become a valuable drug for treating pain relief. Indeed, it is possible, in addition to providing NP relief, that it may have a use in treating osteoarthritic pain, headaches and pain that accompany intestinal diseases.     

Emerging drugs in neuropathic pain

Neuropathic pain is a personally devastating and costly condition affecting 3 – 8% of the population. Existing treatments have limited effectiveness and produce relatively frequent adverse effects. Preclinical research has identified many promising pharmacological targets; however, reliable predictors of success in humans remain elusive. At least 50 new molecular entities have reached clinical development including: glutamate antagonists, cytokine inhibitors, vanilloid-receptor agonists, catecholamine modulators, ion-channel blockers, anticonvulsants, opioids, cannabinoids, COX inhibitors, acteylcholine modulators, adenosine receptor agonists and several miscellaneous drugs. Eight drugs are in Phase III trials at present. Strategies that may show promise over existing treatments include topical therapies, analgesic combinations and, in future, gene-related therapies. Recent years have heralded an explosion of pharmaceutical development in neuropathic pain, reflecting advanced knowledge of neurobiology and a heightened perception of the commercial value of neuropathic pain therapeutics. In the interest of improving patient care, the authors recommend implementing comparative studies throughout the development process in order to demonstrate the increased value of novel agents.     

Factors to consider in the choice of intrathecal drug in the treatment of neuropathic pain

Medication selection for neuropathic pain follows a path of evidence, with respect to appreciating the patient’s entry into the pain care algorithm. As we decide how to approach neuropathic pain, the considerations for intrathecal therapy medication selection are bound by catheter location, region of pain, and patient selection, to name a few. Future research and the 2016 polyanalgesic consensus conference may further provide patient care through a mindful eye on the improvement of patient safety and a reduction of the societal needs of opioids.     

加巴喷丁用于神经病理性疼痛治疗的研究进展

研究表明加巴喷丁(gabapentin)可作用于脊髓背角神经原突触后钙离子通道，从而可能阻断了神经病理性疼痛产生的过程。临床证实加巴喷丁对糖尿病神经病变和带状疱疹后神经痛的治疗效果，是治疗神经病理性疼痛有效的药物。     

葛根素对神经病理性痛模型小鼠的镇痛作用

目的探讨葛根素对神经病理性痛模型小鼠的镇痛作用,为临床开发新的镇痛药物奠定基础。方法结扎雌性C57BL/6小鼠单侧胫神经和腓总神经,建立坐骨神经分支选择损伤(spared nerve injury,SNI)神经病理性痛模型,利用机械刺激法和冷盘法分别观察腹腔注射不同剂量葛根素(100,75和25mg·kg-1)对SNI模型小鼠患侧脚掌痛阈的影响。结果 SNI模型小鼠腹腔注射75mg·kg-1葛根素可显著提高患侧脚掌的50%缩足阈值(P<0.01)和降低5min抬足次数(P<0.01),产生明显的镇痛作用,镇痛时间可维持60～70min;100mg·kg-1葛根素腹腔注射后虽然也可产生明显的镇痛作用,但作用时间较短,仅维持10～20min;25mg·kg-1葛根素腹腔注射后没有明显的镇痛作用。结论适当剂量的葛根素对神经病理性痛具有明显的镇痛作用。     

神经病理性疼痛动物模型

神经病理性疼痛动物模型的不断发展极大地促进了对神经病理性疼痛机制的研究。但是,目前的动物模型仍有很多缺陷,需要不断地完善,对疼痛的观察方法也需要改进。     

通迪胶囊在各类周围神经痛治疗中的临床观察

目的：观察通迪胶囊在各类周围神经痛治疗中的临床效果。方法将60例患者随机分为通迪胶囊治疗组和空心胶囊安慰剂组,每组30例。结果通迪胶囊组有效率99%,安慰剂组有效率为13.3%,两者间差异有统计学意义（P〈0.05）。结论通迪胶囊在各类周围神经痛治疗中有效,值得临床推广使用。     

Sildenafil induces hyperalgesia via activation of the NO-cGMP pathway in the rat neuropathic pain model

Persistent stimulation of nociceptors and C-fibers by tissue injury causes hyperalgesia and allodynia by sensitization of nociceptors and facilitation of synaptic transmission in the spinal cord. The important participant in the inflammatory response of injured peripheral nerve may be nitric oxide (NO). The aim of the present study was to test the sensitivity of PDE5 inhibitor sildenafil in chronic constriction injury (CCI) model a rat model of neuropathic pain. Sciatic nerve injury is associated with development of hyperalgesia 14 days after the nerve ligation. Sildenafil (100 and 200 μg/rat, i.t.) produced a significant decrease in pain threshold, which in lower dose did not alter the nociceptive threshold. The hyperalgesic effect of sildenafil was blocked by L-NAME and methylene blue (MB), which on per se treatment showed antinociceptive effect in nerve ligated rats. The results from the present study indicated that the major activation of NO-cGMP pathway in the chronic constriction injury model of neuropathic pain. The aggravation of hyperalgesic response might be due to the increased cGMP levels resulting in PKG-I activation and its upregulation.