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Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis\u2010associated CPP remain underdeveloped. Here, we examined the role of the voltage\u2010gated sodium (Na\n                    <jats:sub>V<\/jats:sub>\n                    ) channel Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 in (i) the sensitivity of vagina\u2010innervating sensory afferents and investigated whether (ii) Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibition reduces nociceptive signals from the vagina and (iii) ameliorates endometriosis\u2010associated CPP. The mechanical responsiveness of vagina\u2010innervating sensory afferents was assessed with ex vivo single\u2010unit recording preparations. Pain evoked by vaginal distension (VD) was quantified by the visceromotor response (VMR) in vivo. In control mice, pharmacological activation of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 with OD1 sensitised vagina\u2010innervating pelvic afferents to mechanical stimuli. Using a syngeneic mouse model of endometriosis, we established that endometriosis sensitised vagina\u2010innervating pelvic afferents to mechanical stimuli. The highly selective Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitor Tsp1a revealed that this afferent hypersensitivity occurred in a Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7\u2010dependent manner. Moreover, in vivo intra\u2010vaginal treatment with Tsp1a reduced the exaggerated VMRs to VD which is characteristic of mice with endometriosis. Conversely, Tsp1a did not alter ex vivo afferent mechanosensitivity nor in vivo VMRs to VD in Sham control mice. Collectively, these findings suggest that Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 plays a crucial role in endometriosis\u2010induced vaginal hyperalgesia. Importantly, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibition selectively alleviated endometriosis\u2010associated CPP without the loss of normal sensation, suggesting that selective targeting of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 could improve the quality of life of women with endometriosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15795-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15795","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T02:04:36Z","timestamp":1677290676000},"page":"3760-3776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The voltage\u2010gated sodium channel\n                    <scp>\n                      Na\n                      <sub>V<\/sub>\n                      1\n                    <\/scp>\n                    .7 underlies endometriosis\u2010associated chronic pelvic pain"],"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5843","authenticated-orcid":false,"given":"Chun Yuen","family":"Chow","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-9896","authenticated-orcid":false,"given":"Poanna","family":"Tran","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Vetter","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"},{"name":"School of Pharmacy The University of Queensland  Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn F.","family":"King","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"},{"name":"Australian Research Council 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