Resveratrol inhibits the activity of acid‐sensing ion channels in male rat dorsal root ganglion neurons

Resveratrol can relieve pain under various pain conditions. One of the mechanisms of resveratrol analgesia is the regulation of ion channels. Acid-sensing ion channels (ASICs) are expressed predominantly in nociceptive sensory neurons to detect changes in extracellular pH. ASICs are important players in pain associated with tissue acidification. However, it is still unclear whether ASICs are resveratrol targets. Electrophysiological recordings showed that resveratrol decreased acid-induced and ASIC-mediated currents in male rat dorsal root ganglion (DRG) neurons in a concentration-dependent manner. Resveratrol downwardly shifted the concentration–response curve for protons, suggesting that it inhibited ASICs not by changing the pH0.5, but by suppressing the proton-induced maximum response. It also suppressed acid-triggered action potentials in the rat DRG neurons. Finally, intraplantar pretreatment with resveratrol relieved acid-induced nociceptive responses in male rats in a dose-dependent manner. These results indicated that resveratrol inhibited ASIC-mediated electrophysiological activity and nociception, suggesting a novel peripheral mechanism underlying its analgesic effect.