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马拉维若在神经性疼痛治疗中的潜在应用

[Potential application of maraviroc in the therapy of neuropathic pain].

作者信息

Sojka Paweł, Właszczuk Adam, Olakowska Edyta

机构信息

Chair and Department of Physiology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Poland.

出版信息

Pol Merkur Lekarski. 2021 Oct 22;49(293):379-381.

Abstract

According to International Association for the Study of Pain (IASP) neuropathic pain is defined as a pain caused by a lesion or disease of the somatosensory nervous system. In general population 7-8% adults suffer from chronic pain with neuropathic characteristic. The most common causes include: lumbar radiculopathy, postherpetic neuropathy, HIV infection, autoimmune diseases (multiple sclerosis), metabolic diseases (diabetic neuropathy), stroke or spinal cord injury. Current pharmacotherapy of neuropathic pain has insufficient effectiveness, so comprehension of neuropathic pain mechanism is necessary for research of new therapeutic methods. In the study we verify the analgesic effect of maraviroc (antagonist of the chemokine receptor - CCR5) and its potential role in the treatment of neuropathic pain. In the study we focused on dependency between opioid and chemokine receptors, because of similar structure between this receptors occurs cross-desensitization phenomenon. Chemokine antagonist maraviroc belongs to a group of entry inhibitors, antiretroviral drug. It enhances analgesic properties of opioids by inhibition of crossdesensitization of opioid's receptor. Application of maraviroc with morphine can reduce effective dosage of morphine 2,3 fold. Moreover, research show that prophylactic administration of maraviroc without opioid analgesics suppresses development of neuropathic pain symptoms. It has influence on glial phenotype, decreases secretion of proinflammatory cytokines and increases anti-inflammatory cytokine secretion. Furthermore it decreases expression of chemikine receptor mRNA and chemikine ligand's secreted by microglia and astrocytes as a result of nerve injury. We conclude that maraviroc has immunomodulatory properties, potentiates opioid analgesics effect, and can be used in neuropathic pain therapy as a potential co-analgesic.

摘要

根据国际疼痛研究协会(IASP)的定义,神经性疼痛是由躯体感觉神经系统的损伤或疾病引起的疼痛。在普通人群中,7-8%的成年人患有具有神经性特征的慢性疼痛。最常见的病因包括:腰椎神经根病、带状疱疹后神经病变、HIV感染、自身免疫性疾病(多发性硬化症)、代谢性疾病(糖尿病性神经病变)、中风或脊髓损伤。目前神经性疼痛的药物治疗效果不足,因此了解神经性疼痛机制对于研究新的治疗方法很有必要。在本研究中,我们验证了马拉维若(趋化因子受体-CCR5拮抗剂)的镇痛作用及其在神经性疼痛治疗中的潜在作用。在研究中,我们关注阿片类受体与趋化因子受体之间的依赖性,因为这些受体结构相似会出现交叉脱敏现象。趋化因子拮抗剂马拉维若属于一类进入抑制剂,即抗逆转录病毒药物。它通过抑制阿片类受体的交叉脱敏来增强阿片类药物的镇痛特性。将马拉维若与吗啡联合应用可使吗啡的有效剂量降低2.3倍。此外,研究表明,在无阿片类镇痛药的情况下预防性给予马拉维若可抑制神经性疼痛症状的发展。它对神经胶质细胞表型有影响,减少促炎细胞因子的分泌并增加抗炎细胞因子的分泌。此外,它还可降低因神经损伤而由小胶质细胞和星形胶质细胞分泌的趋化因子受体mRNA和趋化因子配体的表达。我们得出结论,马拉维若具有免疫调节特性,可增强阿片类镇痛药的作用,并可作为一种潜在的辅助镇痛药用于神经性疼痛治疗。

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