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

Experimental Neurology
Jessica K AlexanderPhillip G Popovich

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.

References

Aug 19, 1976·Nature·M Devor, P D Wall
Jul 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·J R David
Jun 1, 1980·The Journal of Cell Biology·K D McCarthy, J de Vellis
Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Jul 21, 1998·JAMA : the Journal of the American Medical Association·O GurejeR Gater
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·O MeucciR J Miller
Jan 20, 1999·The Journal of Experimental Medicine·M BozzaJ R David
Jan 20, 2000·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·R W Burry
Jun 10, 2000·Science·C J Woolf, M W Salter
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robert A MitchellRichard Bucala
Jun 10, 2003·The Journal of Comparative Neurology·Julie M SrogaPhillip G Popovich
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Catherine AbbadieMichael J Forrest
Sep 2, 2003·The Journal of Comparative Neurology·Clifford B Saper, Paul E Sawchenko
Sep 23, 2003·Nature Reviews. Immunology·Thierry Calandra, Thierry Roger
Nov 13, 2003·JAMA : the Journal of the American Medical Association·Walter F StewartRichard Lipton
Oct 1, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shuxing WangJianren Mao
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shuxing WangJianren Mao
Jun 15, 2005·Journal of Neurochemistry·Gisela Segond von BanchetHans-Georg Schaible
Jun 25, 2005·Journal of Neuroscience Methods·Zhongshu YangAkiko Nishiyama
Jul 20, 2005·Journal of Neuroimmunology·Melanie S FlintAndrew Baum
Feb 14, 2006·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·A Cüneyt OzaktayJames N Weinstein
Aug 31, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Feng-Quan Zhou, William D Snider
Apr 4, 2007·Journal of Neurochemistry·Kristina A KigerlPhillip G Popovich
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ji ZhangSerge Rivest
Nov 28, 2007·Immunology and Cell Biology·Alex Kudrin, David Ray
Dec 20, 2007·The Journal of Pain : Official Journal of the American Pain Society·C Richard ChapmanChan Woo Song
Mar 26, 2008·Circulation·Alma ZerneckeChristian Weber

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Citations

Jun 26, 2014·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Fuzhou WangRichard M Kream
Dec 19, 2015·Glia·Jonathan-Julio Lorea-HernándezFernando Peña-Ortega
Jan 15, 2014·The Journal of Pain : Official Journal of the American Pain Society·Amanda EllisLinda R Watkins
Jun 7, 2014·Frontiers in Genetics·Hemalatha B RajuJessica K Lerch
May 1, 2016·Histochemistry and Cell Biology·Sanja Vignjević PetrinovićVladan Čokić
May 29, 2015·PloS One·Dimitrios E KouzoukasPedro L Vera
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Wenfu WangYaofeng Zhu
May 10, 2019·Neuromodulation : Journal of the International Neuromodulation Society·Ricardo VallejoDavid L Cedeño
Mar 11, 2020·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Yaping JiRichard J Traub
Jun 15, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·K MorimotoKeiichi Tanaka
Jun 24, 2017·Scientific Reports·Jonathan M Grasman, David L Kaplan
Jan 8, 2020·International Journal of Molecular Sciences·Eric BancroftLee A Shapiro
Jan 25, 2021·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Seyed Mohammad PiriVafa Rahimi-Movaghar
May 1, 2021·Marine Drugs·Eshak I BahbahJesus Simal-Gandara
Apr 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sajad FakhriMasoumeh Jorjani

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