{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:25Z","timestamp":1792785925154,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-142273"],"award-info":[{"award-number":["MOP-142273"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-156084"],"award-info":[{"award-number":["PJT-156084"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Professional Investigator Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does interleukin-1\u03b2 (IL-1\u03b2) play a role in promoting nerve growth factor expression, neurogenesis and deep dyspareunia in endometriosis?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>IL-1\u03b2 directly stimulates nerve growth factor (NGF) expression in endometriosis and is associated with local neurogenesis around endometriosis and more severe deep dyspareunia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Local nerve density around endometriosis (using the pan-neuronal marker PGP9.5) is associated with deep dyspareunia in endometriosis, mediated in part by NGF expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This in vitro study included endometriotic tissue samples from 45 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>This study was conducted in a university hospital affiliated research institute and included 45 women with surgically excised deep uterosacral\/rectovaginal endometriosis (DIE, n\u2009=\u200912), ovarian endometriomas (OMA, n\u2009=\u200914) or superficial peritoneal uterosacral\/cul-de-sac endometriosis (SUP, n\u2009=\u200919). Immunolocalisation of IL-1\u03b2, IL-1 receptor type 1 (IL-1R1), NGF and PGP9.5 in endometriotic tissues was examined by immunohistochemistry (IHC), and the intensity of IHC staining in the endometriotic epithelium and stroma was semi-quantitatively evaluated using the Histoscore method (H-score). For each case, deep dyspareunia was pre-operatively rated by the patient on an 11-point numeric rating scale (0\u201310). In addition, primary endometriosis stromal cells were isolated and cultured from surgically excised endometriosis. These cells were treated with IL-1\u03b2 alone or in combination of Anakinra (an inhibitor of IL-1R1), small inference RNA (siRNA) against IL-1R1, siRNA against c-FOS or NGF neutralising antibody. The mRNA and protein levels of target genes (NGF and c-FOS) were assessed by reverse-transcription qPCR and western blot\/ELISA, respectively. Furthermore, immunofluorescent microscopy was used to examine the neurite growth of rat pheochromocytoma PC-12 cells, as an in vitro model of neurogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>For IHC, IL-1\u03b2 expression in the endometriosis epithelium was significantly associated with more severe deep dyspareunia (r\u2009=\u20090.37, P\u2009=\u20090.02), higher nerve fibre bundle density around endometriosis (r\u2009=\u20090.42, P\u2009=\u20090.01) and greater NGF expression by the endometriosis epithelium (r\u2009=\u20090.42, P\u2009=\u20090.01) and stroma (r\u2009=\u20090.45, P\u2009=\u20090.01). In primary endometriosis stromal cells, treatment with exogenous IL-1\u03b2 significantly increased the mRNA and protein levels of NGF and c-FOS. Pre-treatment with Anakinra, siRNA against IL-1R1, or siRNA against c-FOS, each attenuated IL-1 \u03b2-induced increases of NGF expression. In addition, supernatants from IL-1\u03b2 treated endometriosis stromal cells significantly stimulated PC-12 neurite growth compared to controls, and these effects could be attenuated by pre-treatment with NGF neutralising antibody or Anakinra.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE-SCALE DATA<\/jats:title>\n                    <jats:p>N\/A<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>We did not have data from cultures of endometriosis glandular epithelium, due to the known difficulties with primary cultures of this cell type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Our study revealed a mechanism for deep dyspareunia in endometriosis, whereby IL-1\u03b2 stimulates NGF expression, promoting local neurogenesis around endometriosis, which in turn leads to tender pelvic anatomic sites and thus deep-hitting dyspareunia. There may also be potential for drug targeting of IL-1\u03b2 and\/or NGF in the management of endometriosis-associated pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This study was funded by grants from the Canadian Institutes of Health Research (MOP-142273 and PJT-156084). P.Y. is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB has financial affiliations with Abbvie and Allergan. Otherwise, there are no conflicts of interest to declare.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaa017","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T07:09:04Z","timestamp":1581318544000},"page":"901-912","source":"Crossref","is-referenced-by-count":55,"title":["Role of interleukin-1\u03b2 in nerve growth factor expression, neurogenesis and deep dyspareunia in endometriosis"],"prefix":"10.1093","volume":"35","author":[{"given":"Bo","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, BC Children\u2019s Hospital Research Institute and Women\u2019s Health Research Institute, Vancouver, British Columbia, Canada, V6H3N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad T","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, BC 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