{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:21:18Z","timestamp":1792624878790,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Endometriosis is a gynecological disorder associated with local inflammation and neuroproliferation. Increased nerve bundle density has been attributed to increased expression of nerve growth factor (NGF) and interleukin\u20131\u03b2 (IL-1\u03b2). Immunohistochemical analysis was carried out on 12 patients presenting with all three anatomic subtypes of endometriosis (deep, superficial peritoneal, endometrioma) at surgery, with at least two surgically excised subtypes available for analysis. Immunolocalization for nerve bundle density around endometriosis using protein gene product 9.5 (PGP9.5), as well as NGF and IL-1\u03b2 histoscores in endometriosis epithelium\/stroma, was performed to evaluate differences in scores between lesions and anatomic subtypes per patient. Intra-individual heterogeneity in scores across lesions was assessed using the coefficient of variation (CV). The degree of score variability between subtypes was evaluated using the percentage difference between mean scores from one subtype to another subtype for each marker. PGP9.5 nerve bundle density was heterogenous across multiple subtypes of endometriosis, ranging from 50.0% to 173.2%, where most patients (8\/12) showed CV \u2265 100%. The percentage difference in scores showed that PGP9.5 nerve bundle density and NGF and IL-1\u03b2 expression were heterogenous between anatomic subtypes within the same patient. Based on these observations of intra-individual heterogeneity, we conclude that markers of neuroproliferation in endometriosis should be stratified by anatomic subtype in future studies of clinical correlation.<\/jats:p>","DOI":"10.3390\/biom14050583","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:14:42Z","timestamp":1715753682000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nerve Bundle Density and Expression of NGF and IL-1\u03b2 Are Intra-Individually Heterogenous in Subtypes of Endometriosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4209-2110","authenticated-orcid":false,"given":"Mahfuza","family":"Sreya","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC V6T 2A1, Canada"},{"name":"Women\u2019s Health Research Institute, Vancouver, BC V6H 2N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-6441","authenticated-orcid":false,"given":"Dwayne R.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC V6T 2A1, Canada"},{"name":"Women\u2019s Health Research Institute, Vancouver, BC V6H 2N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC V6T 2A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad T.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-0656","authenticated-orcid":false,"given":"Anna F.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Noga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC V6T 2A1, Canada"},{"name":"Women\u2019s Health Research Institute, Vancouver, BC V6H 2N9, Canada"},{"name":"Centre for Pelvic Pain and Endometriosis, BC Women\u2019s Hospital & Health Centre, Vancouver, BC V6H 3N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-3052","authenticated-orcid":false,"given":"Paul J.","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC V6T 2A1, Canada"},{"name":"Women\u2019s Health Research Institute, Vancouver, BC V6H 2N9, Canada"},{"name":"Centre for Pelvic Pain and Endometriosis, BC Women\u2019s Hospital & Health Centre, Vancouver, BC V6H 3N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Song, S.Y., Jung, Y.W., Shin, W., Park, M., Lee, G.W., Jeong, S., An, S., Kim, K., Ko, Y.B., and Lee, K.H. (2023). Endometriosis-Related Chronic Pelvic Pain. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102868"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(1997). American Society for Reproductive Medicine Revised American Society for Reproductive Medicine Classification of Endometriosis: 1996. Fertil. Steril., 67, 817\u2013821.","DOI":"10.1016\/S0015-0282(97)81391-X"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.12701\/yujm.2020.00444","article-title":"Classification of Endometriosis","volume":"38","author":"Lee","year":"2021","journal-title":"Yeungnam Univ. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/aogs.14099","article-title":"The #Enzian Classification: A Comprehensive Non-Invasive and Surgical Description System for Endometriosis","volume":"100","author":"Keckstein","year":"2021","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s13669-020-00288-8","article-title":"A Proposed Platform for Phenotyping Endometriosis-Associated Pain: Unifying Peripheral and Central Pain Mechanisms","volume":"9","author":"Yong","year":"2020","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/sxmrev\/qead033","article-title":"Neuroproliferative Dyspareunia in Endometriosis and Vestibulodynia","volume":"11","author":"Mwaura","year":"2023","journal-title":"Sex. Med. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1507\/endocrj.EJ13-0027","article-title":"Possible Involvement of Nerve Growth Factor in Dysmenorrhea and Dyspareunia Associated with Endometriosis","volume":"60","author":"Kajitani","year":"2013","journal-title":"Endocr. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1177\/1933719113497279","article-title":"Effect of siRNA against \u03b2-NGF on Nerve Fibers of a Rat Model with Endometriosis","volume":"21","author":"Chen","year":"2014","journal-title":"Reprod. Sci. Thousand Oaks Calif"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.gyobfe.2010.05.005","article-title":"Neurotrophins and pain in endometriosis","volume":"38","author":"Borghese","year":"2010","journal-title":"Gynecol. Obstet. Fertil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1177\/1933719111410711","article-title":"Influence of Nerve Growth Factor in Endometriosis-Associated Symptoms","volume":"18","author":"Arnold","year":"2011","journal-title":"Reprod. Sci. Thousand Oaks Calif"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1007\/s12035-018-1348-6","article-title":"The Expression and Cellular Localisation of Neurotrophin and Neural Guidance Molecules in Peritoneal Ectopic Lesions","volume":"56","author":"Asally","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cyto.2013.03.003","article-title":"Evidence of Neurotrophic Events Due to Peritoneal Endometriotic Lesions","volume":"62","author":"Arnold","year":"2013","journal-title":"Cytokine"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dewanto, A., Dudas, J., Glueckert, R., Mechsner, S., Schrott-Fischer, A., Wildt, L., and Seeber, B. (2016). Localization of TrkB and P75 Receptors in Peritoneal and Deep Infiltrating Endometriosis: An Immunohistochemical Study. Reprod. Biol. Endocrinol. RBE, 14.","DOI":"10.1186\/s12958-016-0178-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.fertnstert.2018.08.016","article-title":"Invasion of Human Deep Nodular Endometriotic Lesions Is Associated with Collective Cell Migration and Nerve Development","volume":"110","author":"Dolmans","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00404-023-07110-9","article-title":"Mechanisms of Peripheral Sensitization in Endometriosis Patients with Peritoneal Lesions and Acyclical Pain","volume":"308","author":"Velho","year":"2023","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1177\/1933719117716778","article-title":"Nerve Growth Factor Is Associated With Sexual Pain in Women With Endometriosis","volume":"25","author":"Peng","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/humrep\/deaa017","article-title":"Role of Interleukin-1\u03b2 in Nerve Growth Factor Expression, Neurogenesis and Deep Dyspareunia in Endometriosis","volume":"35","author":"Peng","year":"2020","journal-title":"Hum. Reprod. Oxf. Engl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000342163","article-title":"Neuroimmunomodulatory Alterations in Non-Lesional Peritoneum Close to Peritoneal Endometriosis","volume":"20","author":"Arnold","year":"2013","journal-title":"Neuroimmunomodulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/1933719117732161","article-title":"Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain","volume":"25","author":"Ding","year":"2018","journal-title":"Reprod. Sci. Thousand Oaks Calif"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2011.08.004","article-title":"Imbalance between Sympathetic and Sensory Innervation in Peritoneal Endometriosis","volume":"26","author":"Arnold","year":"2012","journal-title":"Brain. Behav. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tem.2014.10.003","article-title":"Inflammation and Nerve Fiber Interaction in Endometriotic Pain","volume":"26","author":"McKinnon","year":"2015","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Machairiotis, N., Vasilakaki, S., and Thomakos, N. (2021). Inflammatory Mediators and Pain in Endometriosis: A Systematic Review. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010054"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1177\/1933719115623644","article-title":"Nerve Bundles and Deep Dyspareunia in Endometriosis","volume":"23","author":"Williams","year":"2016","journal-title":"Reprod. Sci. Thousand Oaks Calif"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/cjp2.317","article-title":"KRAS Mutations and Endometriosis Burden of Disease","volume":"9","author":"Orr","year":"2023","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Alotaibi, F.T., Peng, B., Klausen, C., Lee, A.F., Abdelkareem, A.O., Orr, N.L., Noga, H., Bedaiwy, M.A., and Yong, P.J. (2019). Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Endometriosis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219064"},{"key":"ref_27","first-page":"11210","article-title":"Macrophage-Derived Insulin-like Growth Factor-1 Is a Key Neurotrophic and Nerve-Sensitizing Factor in Pain Associated with Endometriosis","volume":"33","author":"Forster","year":"2019","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.fertnstert.2017.01.005","article-title":"Important Role of Collective Cell Migration and Nerve Fiber Density in the Development of Deep Nodular Endometriosis","volume":"107","author":"Orellana","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e230780","DOI":"10.1001\/jamanetworkopen.2023.0780","article-title":"Association of Central Sensitization Inventory Scores with Pain Outcomes After Endometriosis Surgery","volume":"6","author":"Orr","year":"2023","journal-title":"JAMA Netw. Open"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:39Z","timestamp":1760107359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["biom14050583"],"URL":"https:\/\/doi.org\/10.3390\/biom14050583","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]}}}