The effect of caffeic acid on the antinociception and mechanisms in mouse

Antinociceptive profiles of caffeic acid were examined in ICR mice. Caffeic acid 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. Moreover, the cumulative response time of nociceptive behaviors induced by an intraplantar formalin injection was reduced by caffeic acid treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by caffeic acid. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by caffeic acid in the writhing test. However, methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by caffeic acid in the writhing test. Our results suggest that caffeic acid shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of caffeic acid may be mediated by α2-adrenergic and opioidergic receptors, but not serotonergic receptor.