title: Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord.
abstract: In recent years, researchers have begun to pay more attention to the role of Sirtuin 1 (SIRT1, a class III histone deacetylase) in pain. However, little research has been conducted examining the involvement of SIRT1 in chronic morphine tolerance. The aim of this study was to investigate the role of spinal SIRT1 and acetyl-histone H3(Ac-H3) in chronic morphine tolerance in rats. Chronic morphine tolerance was induced by twice-daily intrathecal (i.t.) injections of morphine (10μg) for 6 days. Control rats received normal saline (NS). Resveratrol (Res, a SIRT1 stimulant, 30μg i.t.) or dimethyl sulfoxide (DMSO, 10μl i.t.) was then injected on days 7-13. The thermal paw withdrawal threshold was assessed to determine the analgesic effects of morphine (10μg). qRT-PCR, western blotting and immunohistochemistry were used to detect the expression of SIRT1 and global Ac-H3. Administration of morphine for 6 days induced a stabilized antinociceptive tolerance, down-regulated SIRT1 expression and up-regulated Ac-H3 expression in the spinal dorsal horn. Resveratrol treatment from day 7 to 13 increased SIRT1 expression, suppressed global Ac-H3 expression compared to the morphine tolerance (MT) group, and significantly reversed morphine antinociceptive tolerance. These results suggest that resveratrol reversed morphine tolerance by upregulating the expression of SIRT1 in the spinal dorsal horn. SIRT1 and global Ac-H3 in the spinal cord may play an important role in the mechanisms of chronic morphine tolerance.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ou
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Kemin
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Hunan Provincial Tumor Hospital, Changsha, China.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zou
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China. Electronic address: qulianguo2011@163.com.
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000107:Acetylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004361:Drug Tolerance; D006657:Histones / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D059225:Nociception / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006657:Histones; D009294:Narcotics; D013267:Stilbenes; D009020:Morphine; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Ac-H3; Morphine tolerance; Rat; Resveratrol; SIRT1; Spinal cord