Macrophage migration inhibitory factor (MIF) is essential for inflammatory and neuropathic pain and enhances pain in response to stress

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• 作者：Jessica K. Alex ; er ; Gina M. Cox ; Jin-Bin Tian ; Alicia M. Zha ; Ping Wei ; Kristina A. Kigerl ; Mahesh K. Reddy ; Nilesh M. Dagia ; Theis Sielecki ; Michael X. Zhu ; Abhay R. Satoskar ; Dana M. McTigue ; Caroline C. Whitacre ; Phillip G. Popovich
• 关键词：MIF ; macrophage migration inhibitory factor ; GCs ; glucocorticoids ; WT ; wild type ; CFA ; complete Freund's adjuvant ; DRG ; dorsal root ganglion
• 刊名：Experimental Neurology
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：236
• 期：2
• 页码：351-362
• 全文大小：1778 K

文摘

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. m>Mifm> 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 na?ve 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.