Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance

Pathological pain, a multifaceted and debilitating ailment originating from injury or post-injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti-inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF-κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage-gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.