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Lesion proliferation, vascularization, and associated inflammation are the hallmark features of EM lesions. The legalization of recreational cannabinoids has garnered interest in the patient community and is contributing to a greater incidence of self medication; however, it remains unknown if cannabinoids possess marked disease-modifying properties. In this study, we assess the effects of synthetic cannabinoid, WIN 55212-2 (WIN 55), in EM-representative<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>syngeneic mouse models. WIN 55 reduced proliferation and angiogenesis<jats:italic>in vitro, via<\/jats:italic>MAPK\/Akt-mediated apoptosis. These findings were corroborated in a mouse model of EM, where we found reduced TRPV1 expression in the dorsal root ganglia of the EM mouse model exposed to WIN 55, suggesting reduced signaling of pain stimuli. Ultimately, these pieces of evidence support the use of cannabinoid receptor agonists as a potential therapeutic intervention for EM associated pain and inflammation.<\/jats:p>","DOI":"10.3389\/frph.2021.726936","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T18:58:49Z","timestamp":1633546729000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK\/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis"],"prefix":"10.3389","volume":"3","author":[{"given":"Harshavardhan","family":"Lingegowda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey K.","family":"Symons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Alward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E.","family":"Lomax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Koti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrakant","family":"Tayade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0889-8545(02)00050-5","article-title":"The epidemiology of endometriosis","volume":"30","author":"Missmer","year":"2003","journal-title":"Obstet Gynecol Clin."},{"key":"B2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.ogc.2012.10.002","article-title":"Endometriosis and infertility. 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