Abstract:
: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 naïve 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.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Alexander JK,Cox GM,Tian JB,Zha AM,Wei P,Kigerl KA,Reddy MK,Dagia NM,Sielecki T,Zhu MX,Satoskar AR,McTigue DM,Whitacre CC,Popovich PGdoi
10.1016/j.expneurol.2012.04.018subject
Has Abstractpub_date
2012-08-01 00:00:00pages
351-62issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(12)00190-2journal_volume
236pub_type
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