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

(-)-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., 10-200 mg/kg), oral (p.o., 5-100 mg/kg) or intrathecal (i.t., 0.1-3 mu g/site) routes dose-dependently inhibited glutamate-induced nociception (20 mu mol/paw, pH 7.4) with ID50 values of 139.1 mg/kg; 34.6 mg/kg; and 0.9 mu g/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 (200 mg/kg) given i.p. also reduced significantly the biting response caused by intrathecal injection of glutamate (30 mu g/site), AMPA (25 ng/site), SP (135 ng/site), NMDA (25 ng/site) and kainate (23.5 ng/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 (8.6 mu g/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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.