Oleanolic acid, a pentacyclic triterpene attenuates capsaicin-induced nociception in mice: Possible mechanisms

The anti-inflammatory pentacyclic triterpene, oleanolic acid (OA) was examined on acute nociception induced by intraplantar injection of capsaicin in mice. OA administered orally to mice at 10, 30 and 100 mg kg−1, significantly attenuated the paw-licking response to capsaicin (1.6 μg/paw) by 53%, 68.5% and 36.6%, respectively. Ruthenium red (3 mg kg−1, s.c.), a non-competitive vanilloid receptor (V1, TRPV1)-antagonist also suppressed the capsaicin nociception by 38.6%. The maximal antinociception produced by 30 mg kg−1 OA was significantly blocked in animals pre-treated with naloxone (2 mg kg−1, i.p.), the opioid antagonist; l-arginine (600 mg kg−1, i.p.), the substrate for nitric oxide synthase; or glibenclamide (2 mg kg−1, i.p.), the KATP-channel blocker, but was unaffected by yohimbine (2 mg kg−1, i.p.), an α2-adrenoceptor antagonist. In open-field and rota-rod tests that detect motor deficits, mice received 30 mg kg−1 OA did not manifest any effect per se, indicating that the observed antinociception is not a consequence of motor abnormality. These data suggest that OA inhibits capsaicin-evoked acute nociception due to mechanisms possibly involving endogenous opioids, nitric oxide, and KATP-channel opening.