Activated microglia in the spinal cord underlies diabetic neuropathic pain.
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.
['Wang|Dongmei|D|', 'Couture|Réjean|R|', 'Hong|Yanguo|Y|']
D003929:Diabetic Neuropathies D006801:Humans D017628:Microglia D058990:Molecular Targeted Therapy D009437:Neuralgia D043783:Receptor, Bradykinin B1 D043885:Receptor, Cannabinoid, CB2 D016194:Receptors, N-Methyl-D-Aspartate D013116:Spinal Cord
Microglia Spinal cord Diabetic neuropathic pain Hyperglycemia Bradykinin B1 receptor Proinflammatory cytokines