Mechanisms involved in the antinociceptive effects of orally administered oleanolic acid in the mouse

The antinociceptive effects of oleanolic acid were examined in ICR mice. Oleanolic acid administered orally (1, 5 and 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. In the time- course study, duration of antinociceptive action of oleanolic acid maintained at least for 60 min. In addition, the cumulative nociceptive response time for intraplantar formalin injection (2nd phase), intrathecal injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by oleanolic acid. Intraperitoneal (i.p.) pretreatment with naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) attenuated antinociceptive effect induced by oleanolic acid in the writhing test. However, yohimbine (adrenergic receptor antagonist) did not affect antinociception induced by oleanolic acid. The results indicate that oleanolic acid shows an antinociceptive property in various pain models such as writhing, formalin, substance P and glutamate pain tests. Furthermore, this antinociceptive effect of oleanolic acid may be mediated by opioidergic and serotonergic receptors, but not adrenergic receptors.