The role of TRPV1 receptors in the antinociceptive effect of anandamide at spinal level

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 μg) 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 μg) 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 μg 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.