Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 728, Issue -, Pages 59-66Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2014.01.057
Keywords
Bradykinin B1 receptor; Diabetic neuropathic pain; Hyperglycemia; Microglia; Proinflammatory cytokines; Spinal cord
Categories
Funding
- Natural Science Foundation of China [NSFC-31171072, 31371124]
- Education Ministry of China [20113503110001]
- Canadian Institutes of Health Research [MOP-119329]
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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 pronociceptive 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. (C) 2014 Elsevier B.V. All rights reserved.
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