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 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.


CONCLUSIONS
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.
Batista
Patricia Aparecida
PA
Department of Pharmacology, Center of Biological Science, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
Werner
Maria Fernanda de Paula
MF
Oliveira
Erica Carvalho
EC
Burgos
Leonel
L
Pereira
Patricia
P
Brum
Lucimar Filot da Silva
LF
Story
Gina M
GM
Santos
Adair R S
AR
D000080462:Acyclic Monoterpenes; D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology; D006941:Hyperesthesia / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000473:pathology
D000080462:Acyclic Monoterpenes; D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D039821:Monoterpenes; D005620:Freund's Adjuvant; C018584:linalool