title: Resveratrol attenuates inflammatory hyperalgesia by inhibiting glial activation in mice spinal cords.
abstract: The present study aimed to investigate the effect of resveratrol on inflammatory pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5 consecutive days to induce subacute systemic inflammation. Acetic acid‑induced writhing tests and tail‑flick tests were performed following the final LPS injection. Glial fibrillary acidic protein (GFAP; an astrocyte‑specific activation marker), ionized calcium binding adapter molecule 1 (Iba‑1; a microglia‑specific activation marker) and sirtuin 1 (SIRT1) protein expression levels were detected using immunohistochemistry analysis or western blotting. Following administration of LPS for 5 days, the number of writhes increased and the tail‑flick latency decreased. Resveratrol (10 or 20 mg/kg) partly inhibited LPS‑induced hyperalgesia and prevented the increase in tumor necrosis factor‑α and interleukin 6 levels induced by LPS. LPS injection reduced the SIRT1 protein expression and increased the number of GFAP‑positive and Iba‑1‑positive cells in the spinal cord. Resveratrol increased the SIRT1 protein expression levels and decreased the number of GFAP‑positive and Iba‑1‑positive cells in LPS‑treated mice. The protective effect of resveratrol was partly blocked by a selective SIRT1 inhibitor, EX‑257. Results from the present study suggest that subacute treatment with LPS induced the activation of glial cells and hyperalgesia. Resveratrol was demonstrated to inhibit the activation of glial cells and attenuate inflammatory hyperalgesia in a SIRT1‑dependent manner.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Shi
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Gu
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Jue
authors.initials: J
authors.lastname: Hu
authors.affiliation: Core Facilities, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Song
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D000077185:Resveratrol; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000943:Antigens, Differentiation; D008070:Lipopolysaccharides; D013267:Stilbenes; D000077185:Resveratrol