Authors:
Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M.
Abstract:
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.