The Analgesic and Anxiolytic Activity of Resveratrol Mediated by Different Sub-Types of α-Adrenoceptors of Anterior Cingulate Cortex Following Neuropathic Pain in Male Rats

Background and Objective: The mechanism of analgesic and anxiolytic activity of resveratrol in neuropathic pain conditions remains obscure. The present study was conducted to examine whether the analgesic and anxiolytic activities of resveratrol are associated with α1- and α2-adrenoceptors of the anterior cingulate cortex (ACC), which is a key area of the cortex in the pain process, following neuropathic pain in rats. Materials and Methods: Neuropathic pain was created by chronic constriction injury (CCI) of the sciatic nerve. Male Wistar rats were assigned to the sham, CCI, CCI+resveratrol (40μg/5μL), CCI+resveratrol+prazosin (α1-adrenoceptor antagonist,30μg/5μL), and CCI+resveratrol-Yohimbine (α2-adrenoceptor antagonist, 30μg/5μL) groups. The rats received intra-ACC injection of the drug on the day of CCI and for 6 days post-CCI on a daily basis. Cold allodynia (using acetone test) and anxiety (using elevated plus maze, EPM) were examined on days 2, 4, and 6 following CCI. Results: CCI model significantly increased cold allodynia and anxiety. Resveratrol significantly decreased cold allodynia. Prazosin induced no significant changes in allodynia as compared with the CCI+resveratrol treated group. But the animals in this group had no significant difference from the day before the surgery or compared with the sham group. Prazosin significantly decreased entries into open arms. Additionally, yohimbine significantly increased cold allodynia as compared with the CCI+resveratrol treated group. However, it induced no significant changes in the EPM parameters. Our findings also demonstrated a significant correlation between allodynia and anxiety in CCI rats. Conclusion: It is suggested that the mechanism of analgesic and anxiolytic activities of resveratrol in the ACC of rats is different, and is mediated through α2- and α1-adrenoceptors, respectively.