Role of the NO-cGMP-K + channels pathway in the peripheral antinociception induced by α-bisabolol.

The aim of this study was to examine if the peripheral antinociception of α-bisabolol involves the participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K ⁺ channel opening in the formalin test. Wistar rats were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous injection into the dorsal surface of the paw of vehicles or increasing doses of α-bisabolol (100-300 µg/paw). To determine whether the peripheral antinociception induced by α-bisabolol was mediated by either the opioid receptors or the NO-cGMP-K ⁺ channels pathway, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicles, naloxone, naltrexone, N ^G -nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]-oxadiazolo[4,2-a]quinoxalin-1-one (ODQ), glibenclamide, glipizide, apamin, charybdotoxin, tetraethylammonium, or 4-aminopyridine on the antinociceptive effects induced by local peripheral α-bisabolol (300 µg/paw) were assessed. α-Bisabolol produced antinociception during both phases of the formalin test. α-Bisabolol antinociception was blocked by L-NAME, ODQ, and all the K ⁺ channels blockers. The peripheral antinociceptive effect produced by α-bisabolol was not blocked by the opioid receptor inhibitors. α-Bisabolol was able to active the NO-cGMP-K ⁺ channels pathway to produce its antinoceptive effect. The participation of opioid receptors in the peripheral local antinociception induced by α-bisabolol is excluded.