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

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Naunyn-Schmiedeberg's Arch Pharmacol DOI 10.1007/s00210-014-1007-z

ORIGINAL ARTICLE

Linalool and linalool complexed in β-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia Simone S. Nascimento & Enilton A. Camargo & Josimari M. DeSantana & Adriano A. S. Araújo & Paula P. Menezes & Waldecy Lucca-Júnior & Ricardo L. C. Albuquerque-Júnior & Leonardo R. Bonjardim & Lucindo J. Quintans-Júnior

Received: 26 January 2014 / Accepted: 9 June 2014 # Springer-Verlag Berlin Heidelberg 2014

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 antinociceptive effect of LIN, isolated or in β-cyclodextrin complex (LIN–CD), in an animal model of chronic non-

S. S. Nascimento : E. A. Camargo : L. J. Quintans-Júnior (*) Department of Physiology, Federal University of Sergipe (DFS/UFS), Av. Marechal Rondom, s/n, São Cristóvão, SE, Brazil e-mail: [email protected] L. J. Quintans-Júnior e-mail: [email protected] J. M. DeSantana Department of Physical Therapy, Federal University of Sergipe (DFS/UFS), Aracaju, SE, Brazil A. A. S. Araújo : P. P. Menezes Department of Pharmacy, Federal University of Sergipe (DFS/UFS), Aracaju, SE, Brazil W. Lucca-Júnior Department of Morphology, Federal University of Sergipe (DFS/UFS), Aracaju, SE, Brazil R. L. C. Albuquerque-Júnior Institute of Technology and Research, Tiradentes University, Aracaju, SE, Brazil L. R. Bonjardim Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Brazil

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 < 0.001) of mechanical hyperalgesia on chronic noninflammatory muscle pain model, which remained for 24 h only in LIN–CD, and these compounds significantly (p
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