title: High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes.
abstract: Chronic pain is one of the most common complications of diabetes. However, current treatments for diabetic pain are usually unrealistic because the underlying mechanisms are far from being clear. Immerging studies have implicated immune factors as key players in the diabetic pain. High-mobility group box 1 (HMGB1) is an important mediator of inflammatory response, but its role in diabetic pain is unclear. In the present study, we observed that db/db mice (a model of type 2 diabetes) developed persistent mechanical allodynia from postnatal 2 months. Western blot showed that in postnatal 2-5 months, HMGB1 was significantly higher than that of the heterozygous littermates (db/+) mice. Intrathecal injection of a HMGB1 neutralizing antibody (anti-HMGB1) inhibited mechanical allodynia. Immunostaining data showed that compared with db/+ and C57 mice (postnatal 4 months), glial fibrillary acidic protein (GFAP) staining was significantly increased in the spinal cord of db/db mice. Anti-HMGB1 could effectively decrease GFAP expression. Real-time PCR showed that in postnatal 4 months, db/db mice induced significant increases of TNF-alpha, IL-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in the spinal dorsal horn, while anti-HMGB1 (50 μg) effectively inhibited the up-regulation of these inflammatory mediators. Our results indicate that HMGB1 is significantly up-regulated in the spinal cord of type 2 diabetes, and inhibiting HMGB1 may provide a novel treatment for diabetic pain.
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Ren
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: An
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Lv
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Gao
authors.forename: Xu-De
authors.initials: XD
authors.lastname: Sun
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D059350:Chronic Pain / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein