Antinociceptive profiles and mechanisms of orally administered vanillin in the mice

In the present study, the antinociceptive profiles of vanillin were examined in ICR mice. Vanillin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of vanillin maintained at least for 30 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 A mu g) or glutamate (20 A mu g) injection was not affected by vanillin. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha(2)-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by vanillin in the writhing test. However, phentolamine (alpha(1)-adrenergic receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by vanillin in the writhing test. Our results suggest that vanillin exerts a selective antinociceptive property in the acetic acidinduced visceral inflammatory pain model. Furthermore, this antinociceptive effect of vanillin may be mediated by alpha(2)-adrenergic and opioid receptors, but not alpha(1)-adrenergic and serotonergic receptors.