Antinociceptive effect of resveratrol in carrageenan-evoked hyperalgesia in rats: prolonged effect related to COX-2 expression impairment.

Resveratrol is a natural polyphenol that protects from cancer and cardiovascular diseases. Resveratrol is able to induce apoptotic cell death and it inhibits the cyclooxygenase (COX) cascade. We measured the antinociceptive effect of resveratrol on carrageenan-induced hyperalgesia, prostaglandin-E2 (PGE2) concentration in CSF and COX-1/COX-2 gene expression in the spinal cord and dorsal root ganglion (DRG) in rats. Resveratrol induced a prolonged antinociceptive effect, which was correlated to the inhibition of COX-2 mRNA increase in DRG and cord elicited by carrageenan. An increase in the basal threshold of mechanical nociception was also observed with resveratrol in the absence of any inflammatory insult. A rapid bilateralisation of COX-2 mRNA production, not accompanied by a parallel increase in c-Fos expression, was observed in spinal cord three hours after the inflammatory insult. This increase in COX-2 mRNA concentration in the spinal cord on the opposite side of the inflammatory insult was abolished by resveratrol. In conclusion, the antinociceptive effect exhibited by resveratrol was related to the prevention of COX-2 mRNA increase induced by carrageenan. Resveratrol also prevented the bilateralisation of COX-2 expression. The later effect, together with the prolonged analgesia induced by a single injection, may be of great benefit for preventing chronic pain states often seen after inflammatory insults.