Resveratrol attenuates neuropathic pain through balancing pro-inflammatory and anti-inflammatory cytokines release in mice

• Treatment of RV after CCI relieved neuropathic pain in a dose-dependent manner.
• RV repressed the expression of pro-inflammatory cytokines.
• RV promoted the expression of anti-inflammatory cytokine IL-10.

Anti-inflammatory activity of resveratrol has been widely studied, while its beneficial effect on the management of neuropathic pain, a refractory chronic syndrome with pro-inflammation implicated in, is very little investigated. In the present study, the effects of different doses and various time window of administration of resveratrol were explored in a neuropathic mouse model of chronic constriction injury (CCI) of the sciatic nerve. It was demonstrated that pretreatment of resveratrol (5, 10, 20 and 40 mg/kg) for 7 consecutive days before CCI did not alleviate neuropathic pain, while it clearly relieved the pain when administrated after CCI and such pain relief effect was more pronounced when administrated right after the peak of pain symptom at day 7 after CCI, as evidenced by the alleviation of thermal hyperalgesia and mechanical allodynia. Such a beneficial effect of resveratrol was in a dose-dependent manner. Mechanistic study showed that resveratrol repressed the expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, and promoted the expression of anti-inflammatory cytokine IL-10 at the same time, which was further confirmed in a cell model of microglia. It was also shown that neuropathic pain inversely correlated with pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, but not with anti-inflammatory cytokine IL-10 in all experimental mice from Spearman correlation coefficient. Our study reveals that resveratrol displays a significant neuropathic pain relief effect and paved a way for novel treatment of chronic pain.