Systemic administration of the dietary constituent resveratrol inhibits the nociceptive jaw-opening reflex in rats via the endogenous opioid system

The aim of the present study was to investigate whether, under in vivo conditions, systemic administration of resveratrol could attenuate the rat nociceptive jaw-opening reflex (JOR) via the endogenous opioid system. The JOR evoked by electrical stimulation of the tongue was recorded as digastric muscle electromyograms (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG increased significantly in proportion to the intensity of electrical stimulation (from 1× to 5 × threshold for the JOR). dEMG amplitude in response to 3× threshold electrical stimulation of the tongue was dose-dependently inhibited by intravenous administration of resveratrol (0.5-2 mg/kg). Maximum inhibition of dEMG amplitude was seen within approximately 10 min. These inhibitory effects were reversible, with dEMG responses returning to control levels after approximately 20 min. Pretreatment of rats with naloxone resulted in significant, dose-dependent attenuation of the inhibitory effects of resveratrol on dEMG amplitude compared with control. These findings suggest that resveratrol inhibits the nociceptive JOR via the endogenous opioid system. Further, the findings of the present study strongly support the idea that resveratrol, which is not known to have any toxic side effects, combined with an opioid could be a potential therapeutic agent for the prevention of acute trigeminal nociception.