The role of TRPV1 receptors in the antinociceptive effect of anandamide at spinal level
The role of TRPV1 receptors in the antinociceptive effect of anandamide at spinal level
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DOI：
10.1016/j.pain.2007.04.032
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发表时间：
2008-02-01
期刊：
影响因子：
7.4
通讯作者：
Benedek, Gyoergy
中科院分区：
文献类型：
--
作者：
Horvath, Gyoengyi;Kekesi, Gabriella;Benedek, Gyoergy
虽然众所周知内源性大麻素受体配体大麻素也激活瞬时受体电位香草素1（TRPV1）受体，但还没有体内研究表明TRPV1受体在大麻素在脊髓水平的抗伤害感受作用中的作用。本研究的目的是确定辣椒平抑制TRPV1受体对鞘内给药后花生四烯酸的抗伤害效力的影响。单独的大麻素（1，30或100 μ g）剂量依赖性地减少角叉菜胶诱导的热痛觉过敏，然而，最高剂量引起暂时的兴奋和发声，表明大麻素的疼痛诱导潜力。辣椒平（10或20 μ g）本身并不明显改变疼痛敏感性，但较低剂量增加了疼痛敏感性，较高剂量降低了30 μ g anandamide的抗伤害作用。此外，两种剂量的辣椒平都降低了最大剂量的大麻素的疗效。这些结果表明，TRPV1受体激活在脊髓水平的大麻素的抗伤害性作用中起着重要作用。对TRPV 1受体的抑制作用取决于应用的剂量。我们推测大麻素和TRPV1受体的共同激活通过在脊髓水平释放抗伤害性内源性配体来提供升高的抗伤害性感受。(c)2007年国际疼痛研究协会。Elsevier B.V.出版，保留所有权利。
While it is well known that the endogenous cannabinoid receptor ligand anandamide also activates the transient receptor potential vanilloid1 (TRPV1) receptors, there has been no in vivo study indicating the role of the TRPV1 receptors in the antinociceptive effect of anandamide at spinal level. The goal of this study was to determine the effect of inhibition of TRPV1 receptors by capsazepine on the antinociceptive potency of anandamide after intrathecal administration. Anandamide alone (1, 30 or 100 mu g) dose-dependently decreased carrageenan-induced thermal hyperalgesia, however, the highest dose caused temporary excitation and vocalization, suggesting the pain-inducing potential of anandamide. Capsazepine (10 or 20 mu g) by itself did not change the pain sensitivity markedly, but the lower dose increased it, and the higher dose decreased the antinociceptive effect of 30 mu g anandamide. Furthermore, both doses of capsazepine decreased the efficacy of the largest dose of anandamide. These results show that TRPV1 receptor activation plays a substantial role in the antinociceptive effects of anandamide at spinal level. The effect of the inhibition on TRPV1 receptors depended on the dose applied. We presume that coactivation of the cannabinoid and TRPV1 receptors by anandamide provides elevated antinociception through the release of antinociceptive endogenous ligands at spinal level. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.