Análise dos efeitos do trans-resveratrol sobre a nocicepção espontânea induzida pela capsaicina e glutamato em camundongos

Abstract

Resveratrol (RSV) is a polyphenol with well-characterized anti-inflammatory and antioxidant actions, with some evidence for antinociceptive effects. Herein, we have evaluated the effects of RSV in two acute mouse models of spontaneous nociception, induced by capsaicin and glutamate, with some attempts to define the possible mechanisms of action of this compound. The oral administration of RSV (100 mg/kg) significantly reduced the licking behavior elicited by the intraplantar injection of capsaicin (1.6 μg/paw) or glutamate (10 μmol/paw). The co-administration of RSV, into the mouse paw (25 μg/site), markedly prevented glutamate-induced licking, without affecting capsaicin-elicited responses. Otherwise, the i.t. injection of RSV (300 and 600 μg/site) widely reduced the licking behavior caused by capsaicin, but not by glutamate.Lastly, the i.c.v. injection of RSV (300 μg/site) caused only a mild inhibition of capsaicin-induced nociception, whereas glutamate responses remained unaffected. Unexpectedly, the co-administration of RSV (300 μg/site) was able to inhibit the biting behavior induced by i.t. injection of glutamate (30 μg/site), leaving capsaicin (6.4 μg/site)-induced biting unaltered. Of note, the oral treatment with RSV (100 mg/kg) resulted in a significant inhibition of capsaicin-induced increase of both c-Fos and COX-2 immunolabeling in the lumbar spinal cord, as well as the COX-2 expression in cortex. In glutamate model, the oral administration of RSV failed to affect either c-Fos or COX-2 activation in spinal or brain tissues. Data provides new evidence showing that analgesic effects of RSV are mediated by different mechanisms of action and anatomical sites, depending on the algogenic stimulus.