The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain.
Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.
Costa
Barbara
B
Department of Biotechnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy. barbara.costa@unimib.it
Trovato
Anna Elisa
AE
Comelli
Francesca
F
Giagnoni
Gabriella
G
Colleoni
Mariapia
M
D000284:Administration, Oral; D000818:Animals; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists; D002188:Cannabis / Q000737:chemistry*; D002211:Capsaicin / Q000031:analogs & derivatives; D002908:Chronic Disease; D015232:Dinoprostone / Q000097:blood; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D063387:Cannabinoid Receptor Antagonists; D008054:Lipid Peroxides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; C071423:capsazepine; D002211:Capsaicin