Horvath Gyöngyi, Kekesi Gabriella, Nagy Edit, Benedek György
Department of Physiology, Faculty of Medicine, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary Department of Physiotherapy, Faculty of Health Sciences, University of Szeged, Hungary.
Pain. 2008 Feb;134(3):277-284. doi: 10.1016/j.pain.2007.04.032. Epub 2007 May 29.
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 microg) 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 microg) 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 microg 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.
虽然内源性大麻素受体配体花生四烯乙醇胺（anandamide）也能激活瞬时受体电位香草酸亚型1（TRPV1）受体这一点已广为人知，但尚无体内研究表明TRPV1受体在花生四烯乙醇胺脊髓水平的抗伤害感受作用中所起的作用。本研究的目的是确定辣椒素（capsazepine）抑制TRPV1受体对鞘内注射花生四烯乙醇胺后其抗伤害感受效能的影响。单独给予花生四烯乙醇胺（1、30或100微克）可剂量依赖性地减轻角叉菜胶诱导的热痛觉过敏，然而，最高剂量会引起短暂兴奋和鸣叫，提示花生四烯乙醇胺具有致痛潜力。辣椒素（10或20微克）本身并未显著改变疼痛敏感性，但较低剂量使其增加，而较高剂量则降低了30微克花生四烯乙醇胺的抗伤害感受作用。此外，两种剂量的辣椒素均降低了最大剂量花生四烯乙醇胺的效能。这些结果表明，TRPV1受体激活在花生四烯乙醇胺脊髓水平的抗伤害感受作用中起重要作用。对TRPV1受体的抑制作用取决于所用剂量。我们推测，花生四烯乙醇胺对大麻素受体和TRPV1受体的共同激活通过在脊髓水平释放抗伤害感受性内源性配体来增强抗伤害感受作用。
