SIRT2 overexpression alleviates remifentanil-induced postoperative hyperalgesia through microglia

Abstract

Background: Sirtuin 2 (SIRT2), a member of the mammalian sirtuin family, plays an important role in the pathogenesis of various neurological diseases. However, whether SIRT2 is involved in the regulation of remifentanil-induced postoperative hyperalgesia remains unclear. This study aimed to investigate the potential role of SIRT2 in regulating remifentanil-induced postoperative hyperalgesia.Methods: Remifentanil-induced postoperative hyperalgesia model was established in rats. SIRT2 was over-expressed by injecting recombinant adenoviruses. Nociceptive behaviors of mechanical allodynia and thermal hyperalgesia were measured with paw withdrawal mechanical threshold and paw withdrawal thermal latency, respectively. Iba1 (marker of microglia activation) and SIRT2 levels were detected with Western blot. Iba1 was also measured with immunofluorescence.Results: We found that SIRT2 was downregulated in the spinal cord in remifentanil-induced postoperative hyperalgesia rats. Intrathecal injection of a recombinant plasmid expressing SIRT2 markedly alleviated mechanical allodynia and thermal hyperalgesia in remifentanil-induced postoperative hyperalgesia rats. Iba1 were upregulated after surgical incision and remifentanil infusion, and the up-regulation was more obvious after the combination of surgical incision and remifentanil infusion. Moreover, our results showed that overexpression of SIRT2 inhibited the activation of the microglia in the spinal cord of remifentanil-induced postoperative hyperalgesia rats. Overexpression of SIRT2 significantly attenuated incision- and/or remifentanil induced pronociceptive effects and spinal microglia activation. Conclusions: Overexpression of SIRT2 alleviates remifentanil-induced postoperative hyperalgesia possibly via inhibition of spinal microglia activation. Therefore, SIRT2 may serve as a potential therapeutic target for treatment of neuropathic pain.Trial registration: Not applicable.