Resumo:
Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 mg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 mg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 mg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 mg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 mg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 mg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 mg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.
