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内源性大麻素系统在加巴喷丁对坐骨神经部分结扎诱导的神经性疼痛动物模型的抗痛觉过敏作用中的作用。

Role of the endocannabinoid system on the antihyperalgesic action of gabapentin in animal model of neuropathic pain induced by partial sciatic nerve ligation.

作者信息

Buffon Alexandre C, Javornik Marcelo A, Heymanns Ana C, Salm Daiana C, Horewicz VerÔnica V, Martins Daniel F, Piovezan Anna P

机构信息

Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina/UNISUL, Av. Pedra Branca 25, Pedra Branca, 88137-270 Palhoça, SC, Brazil.

Curso de Medicina, Universidade do Sul de Santa Catarina/UNISUL, Av. Pedra Branca 25, Pedra Branca, 88137-270 Palhoça, SC, Brazil.

出版信息

An Acad Bras Cienc. 2020 Dec 14;92(4):e20191155. doi: 10.1590/0001-3765202020191155. eCollection 2020.

Abstract

Gabapentin has antihyperalgesic action, decreasing central sensitization in neuropathic pain models; this effect depends on the mobilization of endogenous pain control pathways. This study aims to investigate the contribution of the endocannabinoid system to the antihyperalgesic action of gabapentin. Mus musculus Swiss, male, were submitted to PSL. On the 7th and 14th days post PSL, different groups were treated with CB1 receptor antagonist, AM281 via i.t. (2 μg/5 μl) or i.pl. (10 μg/20 μl) or CB2, AM630 via i.t. (5 μL i.t.) or (20 μL i.p.) and 15 min after gabapentin (30 mg / kg orally). Mechanical hyperalgesia was measured by the frequency of paw removal by the von Frey monofilament. Gabapentin demonstrated antihypernociceptive action, which was attenuated in animals pretreated with AM281 in both the i.t. and i.pl routes on the 7th and 14th days, differently from animals pretreated with AM630 that did not achieve a significant reduction with administration i.t. only on the 14th day with administration i.pl. The results show that endocannabinoid system contributes to the antihyperalgesic action of gabapetin in neuropathic pain by PSL, suggesting participation in the medullary and peripheral levels of CB1 receptors, and the peripheral performance of CB2 receptors.

摘要

加巴喷丁具有抗痛觉过敏作用,可降低神经病理性疼痛模型中的中枢敏化;这种作用依赖于内源性疼痛控制途径的激活。本研究旨在探讨内源性大麻素系统在加巴喷丁抗痛觉过敏作用中的作用。选用雄性瑞士小鼠,行坐骨神经结扎术(PSL)。在PSL术后第7天和第14天,不同组分别经鞘内注射(i.t.,2 μg/5 μl)或腹腔注射(i.pl.,10 μg/20 μl)给予CB1受体拮抗剂AM281,或经鞘内注射(5 μL i.t.)或腹腔注射(20 μL i.p.)给予CB2受体拮抗剂AM630,并在口服加巴喷丁(30 mg / kg)15分钟后给药。通过von Frey细丝刺激引起的足爪回缩频率来测量机械性痛觉过敏。加巴喷丁表现出抗伤害感受作用,在第7天和第14天,经i.t.和i.pl途径给予AM281预处理的动物中,该作用减弱;而经AM630预处理的动物,仅在第14天经i.pl途径给药时,i.t.给药未显著降低痛觉过敏。结果表明,内源性大麻素系统通过PSL参与加巴喷丁在神经病理性疼痛中的抗痛觉过敏作用,提示CB1受体在延髓和外周水平发挥作用,CB2受体在外周发挥作用。

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