期刊
EXPERIMENTAL NEUROLOGY
卷 236, 期 2, 页码 351-362出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2012.04.018
关键词
MIF; Pain; Stress; Glucocorticoids; Axon; Neuroplasticity; Microglia; Macrophage; Cytokine; Inflammation
资金
- NIH [R01 NS047175, NS37846, R01 GMK081658, R01 NS059776, AI 064320, P30-NS045758, AI 076309, AI 068829, AI 090803]
- Ray W. Poppleton Endowment
Stress and glucocorticoids exacerbate pain via undefined mechanisms. Macrophage migration inhibitory factor (MIF) is a constitutively expressed protein that is secreted to maintain immune function when glucocorticoids are elevated by trauma or stress. Here we show that MIF is essential for the development of neuropathic and inflammatory pain, and for stress-induced enhancement of neuropathic pain. Mif null mutant mice fail to develop pain-like behaviors in response to inflammatory stimuli or nerve injury. Pharmacological inhibition of MIF attenuates pain-like behaviors caused by nerve injury and prevents sensitization of these behaviors by stress. Conversely, injection of recombinant MIF into naive mice produces dose-dependent mechanical sensitivity that is exacerbated by stress. MIF elicits pro-inflammatory signaling in microglia and activates sensory neurons, mechanisms that underlie pain. These data implicate MIF as a key regulator of pain and provide a mechanism whereby stressors exacerbate pain. MIF inhibitors warrant clinical investigation for the treatment of chronic pain. (C) 2012 Elsevier Inc. All rights reserved.
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