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Macrophages are central to the pathophysiology of endometriosis: they dictate the growth and vascularization of endometriosis lesions and more recently have been shown to promote lesion innervation. The aim of this study was to determine the mechanistic role of macrophages in producing pain associated with endometriosis. Herein, we show that macrophage depletion in a mouse model of endometriosis can reverse abnormal changes in pain behavior. We identified that disease\u2010modified macrophages exhibit increased expression of IGF\u20101 in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of endometriosis\u2010associated macrophages and confirmed expression by lesion\u2010resident macrophages in mice and women. Concentrations of IGF\u20101 were elevated in peritoneal fluid from women with endometriosis and positively correlate with their pain scores. Mechanistically, we demonstrate that macrophage\u2010derived IGF\u20101 promotes sprouting neurogenesis and nerve sensitization\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Finally, we show that the Igf\u20101 receptor inhibitor linsitinib reverses the pain behavior observed in mice with endometriosis. Our data support a role for macrophage\u2010derived IGF\u20101 as a key neurotrophic and sensitizing factor in endometriosis, and we propose that therapies that modify macrophage phenotype may be attractive therapeutic options for the treatment of women with endometriosis\u2010associated pain.\u2014Forster, R., Sarginson, A., Velichkova, A., Hogg, C., Doming, A., Home, A. W., Saunders, P. T. K., Greaves, E. Macrophage\u2010derived insulin\u2010like growth factor\u20101 is a key neurotrophic and nerve\u2010sensitizing factor in pain associated with endometriosis. FASEB J. 33, 11210\u201311222 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900797r","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T04:00:40Z","timestamp":1562817640000},"page":"11210-11222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":164,"title":["Macrophage\u2010derived insulin\u2010like growth factor\u20101 is a key neurotrophic and nerve\u2010sensitizing factor in pain associated with endometriosis"],"prefix":"10.1096","volume":"33","author":[{"given":"Rachel","family":"Forster","sequence":"first","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sarginson","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanaska","family":"Velichkova","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Hogg","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Dorning","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Horne","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health The University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa T. 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