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加巴喷丁类药物对大鼠背根神经节原代培养物对炎症或躯体感觉刺激反应的影响。

Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli.

机构信息

Department of Veterinary-Physiology and -Biochemistry, Justus-Liebig University, Frankfurter Strasse 100, D-35392 Giessen, Germany.

Department of Veterinary Clinical Sciences, Small Animal Clinic, Justus-Liebig University, Frankfurter Strasse 108, D-35392 Giessen, Germany.

出版信息

J Basic Clin Physiol Pharmacol. 2020 Feb 20;31(4):/j/jbcpp.2020.31.issue-4/jbcpp-2019-0261/jbcpp-2019-0261.xml. doi: 10.1515/jbcpp-2019-0261.

Abstract

Background Gabapentinoids are known to reduce neuropathic pain. The aim of this experimental study was to investigate whether gabapentinoids exert anti-inflammatory and/or anti-nociceptive effects at the cellular level using primary cultures of rat dorsal root ganglia (DRG). Methods Cells from rat DRG were cultured in the presence of gabapentin or pregabalin, and we tested the effects of subsequent stimulation with lipopolysaccharide (LPS) on the expression of genes (real-time polymerase chain reaction) and production of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) by specific bioassays. Using Ca2+ imaging, we further investigated in neurons the effects of gabapentinoids upon stimulation with the TRPV-1 agonist capsaicin. Results There is a small influence of gabapentinoids on the inflammatory response to LPS stimulation, namely, a significantly reduced expression of IL-6. Pregabalin and gabapentin further seem to exert a moderate inhibitory influence on capsaicin-induced Ca2+ signals in DRG neurons. Conclusions Although the single inhibitory effects of gabapentinoids on inflammatory and nociceptive responses are moderate, a combination of both effects might provide an explanation for the proposed function of these substances as an adjuvant for the reduction of neuropathic pain.

摘要

背景

加巴喷丁类药物已被证实可减轻神经性疼痛。本实验研究旨在通过大鼠背根神经节(DRG)原代培养物,探究加巴喷丁类药物在细胞水平是否具有抗炎和/或抗伤害感受作用。

方法

在存在加巴喷丁或普瑞巴林的情况下培养大鼠 DRG 细胞,并通过特定的生物测定检测随后用脂多糖(LPS)刺激对基因表达(实时聚合酶链反应)和肿瘤坏死因子-α(TNFα)和白细胞介素-6(IL-6)产生的影响。通过钙成像,我们进一步研究了加巴喷丁类药物对 TRPV-1 激动剂辣椒素刺激下神经元的影响。

结果

加巴喷丁类药物对 LPS 刺激引起的炎症反应有轻微影响,即 IL-6 的表达显著降低。普瑞巴林和加巴喷丁对 DRG 神经元中辣椒素诱导的 Ca2+信号似乎还有一定的抑制作用。

结论

尽管加巴喷丁类药物对炎症和伤害感受反应的单一抑制作用是适度的,但两者的结合可能为这些物质作为减轻神经性疼痛的辅助药物的作用提供解释。

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