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 μg/site) routes dose-dependently inhibited glutamate-induced nociception (20 μmol/paw, pH 7.4) with ID50 values of 139.1 mg/kg; 34.6 mg/kg; and 0.9 μg/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 μg/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 μg/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.