title: Minocycline attenuates pain by inhibiting spinal microglia activation in diabetic rats.
abstract: The mechanisms associated with diabetes-induced neuropathic pain are complex and poorly understood. In order to understand the involvement of spinal microglia activity in diabetic pain, the present study investigated whether minocycline treatment is able to attenuate diabetic pain using a rat model. Diabetes was induced using a single intraperitoneal injection of streptozotocin (STZ). Minocycline was then intrathecally administered to the rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested weekly. The expression of OX-42, Iba-1, phospho-p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS), were examined in the spinal cord in order to evaluate the activation of microglia. The present study demonstrated that rats with STZ-induced diabetes exhibited increased mean plasma glucose concentration, decreased mean body weight and significant pain hypersensitivity compared with control rats. PWT and PWL values of rats with STZ-induced diabetes increased following treatment with minocycline. No differences were observed in expression levels of the microglial activity markers (OX-42, Iba-1 and phospho-p38 MAPK) between rats with STZ-induced diabetes and control rats. However, TNF-α, IL-1β and iNOS expression levels were higher in rats with STZ-induced diabetes compared with control rats. Following treatment with minocycline markers of microglial activation, including cytokines and iNOS, were downregulated in rats with STZ-induced diabetes. The results of the present study indicated that minocycline treatment may inhibit spinal microglial activation and attenuate diabetic pain in rats with STZ-induced diabetes.
authors.affiliation: Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, No. 474 Hospital of Chinese People's Liberation Army, Urumqi, Xinjiang 830013, P.R. China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Yong-Zhen
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Zhao-Shen
authors.initials: ZS
authors.lastname: Li
authors.affiliation: Department of Anatomy and K. K. Leung Brain Research Center, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D008911:Minocycline / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D010146:Pain / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000700:Analgesics; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D008911:Minocycline