Antinociceptive mechanisms of orally administered decursinol in the mouse

Antinociceptive profiles of decursinol were examined in ICR mice. Decursinol administered orally (from 5 to 200 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured by the tail-flick and hot-plate tests. In addition, decursinol attenuated dose-dependently the writhing numbers in the acetic acid-induced writhing test. Moreover, the cumulative response time of nociceptive behaviors induced by an intraplantar formalin injection was reduced by decursinol treatment during the both 1st and 2nd phases in a dose-dependent manner. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of TNF-alpha (100 pg), IL-1 beta (100 pg), IFN-gamma (100 pg), substance P (0.7 microg) or glutamate (20 microg) was dose-dependently diminished by decursinol. Intraperitoneal (i.p.) pretreatment with yohimbine, methysergide, cyproheptadine, ranitidine, or 3,7-dimethyl-1-propargylxanthine (DMPX) attenuated inhibition of the tail-flick response induced by decursinol. However, naloxone, thioperamide, or 1,3-dipropyl-8-(2-amino-4-chloro-phenyl)-xanthine (PACPX) did not affect inhibition of the tail-flick response induced by decursinol. Our results suggests that decursinol shows an antinociceptive property in various pain models. Furthermore, antinociception of decursinol may be mediated by noradrenergic, serotonergic, adenosine A(2), histamine H(1) and H(2) receptors.