Linalool and linalool complexed in β-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia

Abstract

The analgesic activity of (-)-linalool (LIN), a monoterpene present in essential oils of Lamiaceae species, has been previously demonstrated in rodents. However, its possible use in the treatment of fibromyalgia (FM) was never demonstrated. Additionally, as a short half-life is a limitation for the LIN medicinal application, the employment of drug delivery systems has been used to improve pharmaceutical properties of this compound. We investigated the anti-nociceptive effect of LIN, isolated or in β-cyclodextrin complex (LIN-CD), in an animal model of chronic non-inflammatory muscle pain (a FM animal model), as well as its effect on the central nervous system (CNS). Male Swiss mice were subjected to two injections of acidic saline (pH 4; 20 μL/gastrocnemius) and were treated on alternate days, with LIN-CD (25 mg/kg, p.o.), LIN (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.), or vehicle (neutral saline). After 60 min, they were screened for mechanical hyperalgesia (von Frey), motor coordination (rotarod), and muscle strength (grip strength meter) for 27 days. The CNS areas involved in the anti-hyperalgesic activity were evaluated by immunofluorescence. LIN or LIN-CD produced a significant reduction (p∈