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However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits. Mechanosensitivity of vagina\u2010innervating primary afferents was examined using an ex vivo single\u2010unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1\/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin\u20101 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitization of spinal circuitry in endometriosis. These results demonstrate endometriosis\u2010induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain relief treatments for this debilitating disorder.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15843-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15843","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T08:41:56Z","timestamp":1683794516000},"page":"3777-3800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Peripheral and central neuroplasticity in a mouse model of endometriosis"],"prefix":"10.1111","volume":"168","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-2224","authenticated-orcid":false,"given":"Joel","family":"Castro","sequence":"first","affiliation":[{"name":"Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park South Australia Australia"},{"name":"Hopwood Centre for Neurobiology, Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Maddern","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park South Australia Australia"},{"name":"Hopwood Centre for Neurobiology, Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andelain","family":"Erickson","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park South Australia Australia"},{"name":"Hopwood Centre for Neurobiology, Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park South Australia Australia"},{"name":"Hopwood Centre for Neurobiology, Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Brierley","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park South Australia Australia"},{"name":"Hopwood Centre for Neurobiology, Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"Discipline of Medicine University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.03.046"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916688219"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.08.004"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-012110-142158"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182a7e1f5"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.01.032"},{"issue":"185","key":"e_1_2_12_8_1","article-title":"Enterochromaffin cells are gut Chemosensors that couple to sensory neural pathways","volume":"170","author":"Bellono N. 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