The antinociceptive effect of (-)-linalool in models of chronic inflammatory and neuropathic hypersensitivity in mice

J Pain. 2010 Nov;11(11):1222-9. doi: 10.1016/j.jpain.2010.02.022. Epub 2010 May 8.


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 ( 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 administration of inflammatory mediators. Therefore, we injected the cytokines IL-1β (.1 pg/site) and TNF-α (1 pg/site) intrathecally. (-)-Linalool inhibited the biting response induced by IL-1β and TNF-α.

Perspective: The article adds information about antinociceptive properties of (-)-linalool 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Adjuvants, Immunologic / toxicity
  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant / toxicity
  • Hyperalgesia / drug therapy
  • Hyperalgesia / pathology
  • Hyperesthesia / drug therapy
  • Hyperesthesia / pathology
  • Inflammation Mediators / pharmacology*
  • Inflammation Mediators / therapeutic use
  • Mice
  • Monoterpenes / pharmacology*
  • Monoterpenes / therapeutic use
  • Neuralgia / drug therapy
  • Neuralgia / pathology
  • Neuralgia / prevention & control*
  • Sciatic Neuropathy / drug therapy
  • Sciatic Neuropathy / pathology


  • Acyclic Monoterpenes
  • Adjuvants, Immunologic
  • Inflammation Mediators
  • Monoterpenes
  • Freund's Adjuvant
  • linalool