Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats

Abstract

Neuropathic pain is clinically unsatisfactorily treated because of unclear mechanisms. The present study aims to explore the concrete mechanisms underlying the alleviation of resveratrol-activated silent information regulator 1 (Sirt1) to chronic constriction injury (CCI)-induced neuropathic pain. CCI surgery was conducted to the unilateral sciatic nerve of male Sprague-Dawley rats to induce neuropathic pain experimentally. Resveratrol with or without miR-182 antagomir were administered to CCI rats via intrathecal catheter. Behavioral tests including paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were conducted to explore mechanical allodynia and thermal hyperalgesia. Western blot, qRT-PCR were used to detect the expression levels of Sirt1, miR-182, and Nav1.7 in CCI dorsal root ganglions (DRGs). CCI rats displayed lower PWT and PWL compared with the sham control. Also, the CCI DRGs displayed lower Sirt1 and miR-182 expression as well as higher Nav1.7 expression, which would be almost reversed by resveratrol treatment for 4 successive days. We also found that miR-182 expression inhibition erased the analgesia effect of resveratrol to CCI–induced neuropathic pain possibly through upregulating Nav1.7 expression. In summary, resveratrol alleviated CCI–induced neuropathic pain, possibly through activating Sirt1 to suppress Nav1.7 expression via upregulating miR-182 expression in CCI DRGs.