(-)-Linalool produces antinociception in two experimental models of pain

Linalool is a monoterpene compound commonly found as a major component of the essential oils of several aromatic plant species, many of which are used in traditional medical systems as analgesic and anti-inflammatory remedies. We previously reported that (-)-linalool, the natural occurring enantiomer, plays a major role in the anti-inflammatory activity displayed by different essential oils, suggesting that linalool-producing species are potentially anti-inflammatory agents. In this study, the antinociceptive activity of (-)-linalool was examined in two different pain models in mice: the acetic acid-induced writhing response, a model of inflammatory pain, and the hot plate test, a model of supraspinal analgesia. Moreover, the effect of (-)-linalool on spontaneous locomotor activity (25, 50, 75 and 100 mg/kg) was evaluated. The results show that this compound induced a significant reduction of the acid-induced writhing at doses ranging from 25 to 75 mg/kg. Such effect was completely reversed both by the opioid receptor antagonist naloxone and by the unselective muscarinic receptor antagonist atropine. In the hot plate test, only the dose of 100 mg/kg of (-)-linalool resulted in a significant effect. (-)-Linalool induced a dose dependent increase of motility effects, thus ruling out the confounding influence of a possible sedative effect. The more pronounced effect of (-)-linalool on the writhing test with respect to the hot plate test is consistent with the observation that (-)-linalool possesses anti-inflammatory activity. Finally, the activation of opioidergic and cholinergic systems appears to play a crucial role in (-)-linalool-induced antinociception.