The Antinociceptive Effect of (-)-Linalool in Models of Chronic Inflammatory and Neuropathic Hypersensitivity in Mice

We used multiple pain models to investigate the effects of ( ) linalool a monoterpene alcohol present in the essential oil of plants on chronic inflammatory and neuropathic hypersensitivity in adult Swiss mice Inflammatory or neuropathic hypersensitivity was induced by intraplantar (i pl) injection of complete Freund s adjuvant (CFA) or partial sciatic nerve ligation (PSNL) respectively Twenty four hours after CFA injection we used Von Frey filaments and acetone evoked cooling to evaluate tactile and thermal hypersensitivity respectively A single i p injection of ( ) linalool (50 or 200 mg/kg) administered 30 minutes before testing reduced CFA induced mechanical hypersensitivity Similarly ( ) linalool reduced acetone evoked hypersensitivity up to 4 hours after treatment Compared with vehicle ( ) linalool produced a marked reduction in CFA induced paw edema ( ) Linalool also reduced mechanical hypersensitivity induced by PSNL 7 days after injury Multiple ( ) linalool treatments given chronically (twice a day for 10 days 50 mg/kg i p) significantly reduced mechanical hypersensitivity induced by CFA and PSNL This multidose strategy did not cause tolerance We also reasoned that ( ) linalool might reduce nociceptive behavior in response to direct ad ministration of inflammatory mediators Therefore we injected the cytokines IL 10 1 beta ( 1 pg/site) and TNF alpha (1 pg/site) intrathecally ( ) Linalool inhibited the biting response induced by IL 1 beta and TNF alpha Perspective The article adds information about antinociceptive properties of ( ) hnalool in chronic inflammatory and neuropathic hypersensitivity It also indicates that ( ) linalool might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain (C) 2010 by the American Pain Society