Nerve fibers in endometriosis: pain pathogenesis and new approaches to diagnosis

L.V. Adamyan, М. М. Сонова, O. V. Paklina, E.A. Karapetyan, K. N. Arslanyan
In: Russian Journal of Human Reproduction · 2026 · vol. 32(2) , pp. 54 · doi:10.17116/repro20263202154 · W7156197642
article OA: closed CC0
Full text JSON View on OpenAlex View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review analyzes the role of PGP 9.5 as a marker for nerve fibers in endometriosis pain pathogenesis and diagnosis, highlighting its potential and current limitations for clinical use.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This paper reviews how nerve fibers contribute to endometriosis-associated pain pathogenesis and discusses emerging diagnostic approaches, focusing on evidence from histological/immunohistochemical studies and biomarker concepts. It summarizes findings that suggest increased or altered innervation in endometriotic lesions (especially deep infiltrating lesions) and in some relevant tissue layers, linking these neural changes with pain mechanisms such as peripheral sensitization and hyperalgesia. A key limitation is that the evidence base and diagnostic performance vary across studies and tissue sampling approaches, and the review format does not provide uniform, pooled effectiveness estimates. This paper is centrally about endometriosis — it focuses specifically on nerve fibers in endometriosis pain pathogenesis and new diagnostic approaches.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Genital endometriosis is a chronic multisystem disease in which pain syndrome remains the leading clinical manifestation. Despite significant advances in understanding the pathogenesis of endometriosis, the mechanisms of pain generation and the reasons for the discrepancy between the extent of morphological lesions and the severity of clinical symptoms remain the subject of active investigation. In recent years, increasing attention has been paid to the role of nerve fibers and neuroimmune interactions in the development of endometriosis-associated pain. The aim of this review is to analyze current data on the role of protein gene product 9.5 (PGP 9.5) as an immunohistochemical marker of nerve fibers in the pathogenesis of pain syndrome and in the diagnosis of endometriosis. The review addresses contemporary concepts of neuronal and neuroimmune mechanisms of pain, features of innervation of the eutopic endometrium and endometriotic lesions, as well as the potential for nerve fiber detection using PGP9.5. Particular emphasis is placed on data regarding the association between nerve fiber density and pain severity, as well as on the prospects for the use of this marker in minimal and early forms of the disease. The analysis of the literature indicates that PGP9.5 is a sensitive and biologically substantiated marker reflecting the neuronal component of endometriosis. At the same time, its use in clinical practice is limited by methodological heterogeneity among studies, the lack of standardized protocols for quantitative assessment, and the absence of universal diagnostic thresholds. At present, PGP9.5 should be regarded as an auxiliary and research tool, the application of which is feasible within comprehensive diagnostic algorithms. Further studies aimed at standardizing methodologies and validating diagnostic criteria are required to clarify the clinical relevance of this approach.
Full text 7,839 characters · extracted from oa-doi-fallback · click to expand
Сайт издательства «Медиа Сфера» содержит материалы, предназначенные исключительно для работников здравоохранения. Закрывая это сообщение, Вы подтверждаете, что являетесь дипломированным медицинским работником или студентом медицинского образовательного учреждения. Результаты поиска: 0 Нервные волокна при эндометриозе: патогенез боли и новые подходы к диагностике Журнал: Проблемы репродукции. 2026;32(2): 54‑62 Прочитано: 212 раз Как цитировать: Литература / References: - Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstetrics and Gynecology Clinics of North America. 1997;24(2):235-258. https://doi.org/10.1016/S0889-8545(05)70302-8 - Адамян Л.В., Андреева Е.Н. Эндометриоз и его глобальное воздействие на организм женщины. Проблемы репродукции. 2022;28(1):54-64. https://doi.org/10.17116/repro20222801154 - Hadfield R, Mardon H, Barlow DH, Kennedy S. Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Human Reproduction. 1996;11(4):878-880. https://doi.org/10.1093/oxfordjournals.humrep.a019270 - Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E. ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction. 2005;20(10):2698-2704. https://doi.org/10.1093/humrep/dei135 - Адамян Л.В., Михайлова Е.А., Пивняк О.В., Власова И.В. Объективизация боли у пациенток с эндометриозом: обзор литературы и собственные данные. Информационный вестник ВОГиС. 2022;48(2):24-31. - McKinnon BD, Bertschi D, Bersinger NA, Mueller MD. Inflammation and nerve fiber interaction in endometriotic pain. Trends in Endocrinology and Metabolism. 2015;26(1):1-10. https://doi.org/10.1016/j.tem.2014.10.003 - Yan D, Liu X, Guo S-W. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2017;209:14-24. https://doi.org/10.1016/j.ejogrb.2016.06.017 - Velho RV, Sehouli J, Mechsner S. Mechanisms of peripheral sensitization in endometriosis patients with peritoneal lesions and acyclical pain. Archives of Gynecology and Obstetrics. 2023;308(4):1327-1340. https://doi.org/10.1007/s00404-023-06990-6 - Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F, Noel J-C. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Human Reproduction. 2002;17(7):1895-1900. https://doi.org/10.1093/humrep/17.7.1895 - Tokushige N, Markham R, Russell P, Fraser IS. High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Human Reproduction. 2006;21(3): 782-787. https://doi.org/10.1093/humrep/dei368 - Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. Human Reproduction. 2006;21(11):3001-3007. https://doi.org/10.1093/humrep/del260 - Wang G, Tokushige N, Markham R, Fraser IS. Rich innervation of deep infiltrating endometriosis. Human Reproduction. 2009;24(4): 827-834. https://doi.org/10.1093/humrep/den464 - Tokushige N, Markham R, Russell P, Fraser IS. Different types of small nerve fibers in eutopic endometrium and myometrium in women with endometriosis. Fertility and Sterility. 2007;88(4): 795-803. https://doi.org/10.1016/j.fertnstert.2006.12.078 - Donnez O, Soares M, Defrère S, Van Kerk O, Van Langendonckt A, Donnez J, Colette S, Dolmans M-M. Nerve fibers are absent in disease-free and eutopic endometrium, but present in endometriotic (especially deep) lesions. Journal of Endometriosis. 2013; 5(2):68-76. https://doi.org/10.5301/je.5000155 - Alotaibi FT. Pathophysiology of endometriosis: insights from immunohistochemical analysis of ectopic and eutopic tissues. International Journal of Molecular Sciences. 2025;26(13):5998. https://doi.org/10.3390/ijms26135998 - Zoet G, Tucker DR, Orr NL, Alotaibi FT, Liu YD, Noga H, Köbel M, Yong PJ. Standardized protocol for quantification of nerve bundle density as a biomarker for endometriosis. Frontiers in Reproductive Health. 2023;5:1297986. https://doi.org/10.3389/frph.2023.1297986 - Al-Jefout M, Dezarnaulds G, Cooper M, Tokushige N, Luscombe GM, Markham R, Fraser IS. Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study. Human Reproduction. 2009;24(12):3019-3024. https://doi.org/10.1093/humrep/dep275 - Aghaey Meibody F., Mehdizadeh Kashi A., Zare Mirzaie A., Ghajarie Bani Amam M., Shariati Behbahani A., Zolali B., Najafi L. Diagnosis of endometrial nerve fibers in women with endometriosis. Archives of Gynecology and Obstetrics. 2011;284(5):1157-1162. https://doi.org/10.1007/s00404-010-1806-5 - Bokor A, Kyama CM, Vercruysse L, Fassbender A, Gevaert O, Vodolazkaia A, De Moor B, Fülöp V, D’Hooghe T. Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis. Human Reproduction. 2009;24(12):3025-3032. https://doi.org/10.1093/humrep/dep283 - Bano S, Pradhan D, Behera PK, Kar A, Mishra A, Kar T. Diagnosis of endometriosis by detection of nerve fibers using protein gene product 9.5 immunohistochemistry. Journal of Current Research in Scientific Medicine. 2021;7(2):72-76. https://doi.org/10.4103/jcrsm.jcrsm_49_21 - Chikkala H, Prabhu K, Chandrasekaran S, Shanthamani PM. Detection of endometrial nerve fibres in the diagnosis of endometriosis: a case-control study. The Journal of Obstetrics and Gynecology of India. 2021;71(3):263-268. https://doi.org/10.1007/s13224-020-01412-3 - Yadav G, Rao M, Gothwal M, Singh P, Kathuria P, Sharma PP. Detection of nerve fibers in the eutopic endometrium of women with endometriosis, uterine fibroids and adenomyosis. Journal of Clinical and Diagnostic Research. 2018;12(7):QC01-QC05. https://doi.org/10.7860/JCDR/2018/35884.12811 - Sommar A, Meier J, Borgfeldt C, Andersson S, Stålnacke B-M. Influence of endometrial nerve fibers and hormones on pain in women with endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2025;310:113950. https://doi.org/10.1016/j.ejogrb.2025.113950 - Zhang C, Dai Y, Zhang J, Li X, Jia S, Shi J, Leng J. Distribution of nerve fibers in abdominal wall endometriosis and their clinical significance. Journal of Obstetrics and Gynaecology Research. 2022; 48(5):1160-1168. https://doi.org/10.1111/jog.15234 - Guan Q, Zhang D, Li X, Wang Y, Zhang Y, Liu Y, Chen Z. Nociceptin/orphanin FQ opioid peptide-receptor expression in the endometriosis-associated nerve fibers — possible treatment option? Cells. 2023;12(10):1395. https://doi.org/10.3390/cells12101395 - Guan Q. Nociceptin/orphanin FQ opioid peptide receptor-related ligands as potential analgesics in endometriosis-associated pain. Dissertation. 2024. Accessed March 18, 2026. https://refubium.fu-berlin.de/bitstream/handle/fub188/45018/Guan__Qihui-dissertation.pdf?sequence=3&isAllowed=y - Shafrir AL, Saunders PTK. Editorial: participant characteristics and biological markers for endometriosis diagnosis or prediction of treatment response. Frontiers in Reproductive Health. 2023;4: 1023456. https://doi.org/10.3389/frph.2023.1023456 - Liu H, Lang J-H. Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis. Medical Science Monitor. 2011;17(4):RA92-RA99. https://doi.org/10.12659/MSM.881707 Подтверждение e-mail На [email protected] отправлено письмо со ссылкой для подтверждения e-mail. Перейдите по ссылке из письма, чтобы завершить регистрацию на сайте. Подтверждение e-mail Мы используем файлы cооkies для улучшения работы сайта. Оставаясь на нашем сайте, вы соглашаетесь с условиями использования файлов cооkies. Чтобы ознакомиться с нашими Положениями о конфиденциальности и об использовании файлов cookie, нажмите здесь.

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (22)

Source provenance

openalex
last seen: 2026-06-04T00:00:01.174412+00:00
unpaywall
last seen: 2026-06-02T02:00:03.124865+00:00
License: CC0 · commercial use OK