title: Activated microglia in the spinal cord underlies diabetic neuropathic pain.
abstract: Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP.
authors: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, New campus, Fuzhou, Fujian 350108, People׳s Republic of China.
authors: Dongmei
authors: D
authors: Wang
authors: Department of Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Downtown, Montréal, Québec, Canada H3C 3J7.
authors: Réjean
authors: R
authors: Couture
authors: College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, New campus, Fuzhou, Fujian 350108, People׳s Republic of China. Electronic address: yhong@fjnu.edu.cn.
authors: Yanguo
authors: Y
authors: Hong
mesh_terms: D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D043783:Receptor, Bradykinin B1; D043885:Receptor, Cannabinoid, CB2; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Bradykinin B1 receptor; Diabetic neuropathic pain; Hyperglycemia; Microglia; Proinflammatory cytokines; Spinal cord