Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice.

摘要

(-)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (-)-linalool has anti-inflammatory, antihyperalgesic and antinociceptive properties in different animal models. The present study investigated the contribution of glutamatergic system in the antinociception elicited by (-)-linalool in mice. Nociceptive response was characterized by the time that the animal spent licking the injected hind paw or biting the target organ following glutamate receptor agonist injections. (-)-Linalool administered by intraperitoneal (i.p., 10-200mg/kg), oral (p.o., 5-100mg/kg) or intrathecal (i.t., 0.1-3mug/site) routes dose-dependently inhibited glutamate-induced nociception (20mumol/paw, pH 7.4) with ID(50) values of 139.1mg/kg; 34.6mg/kg; and 0.9mug/site, with inhibitions of 70+/-4; 72+/-7 and 74+/-8%, respectively. However, the intraplantar injection of (-)-linalool partially (49+/-9%) inhibited glutamate-induced nociception. Furthermore, (-)-linalool (200mg/kg) given i.p. also reduced significantly the biting response caused by intrathecal injection of glutamate (30mug/site), AMPA (25ng/site), SP (135ng/site), NMDA (25ng/site) and kainate (23.5ng/site), with inhibitions of 89+/-6%, 73+/-11%, 85+/-4%, 98+/-2% and 52+/-15%, respectively. However, (-)-linalool did not inhibit nociception induced by intrathecal injection of trans-ACPD (8.6mug/site). Taken together, these results provide experimental evidences indicating that (-)-linalool produce marked antinociception against glutamate induced pain in mice, possible due mechanisms operated by ionotropic glutamate receptors, namely AMPA, NMDA and kainate.