Neuroangiogenesis, neuroimmune interactions and markers of pathological innervation in the development of endometriosis-associated pain. Part I. Biological markers in pain pathogenesis
Asaturova A.V., Tambieva F.R., Rogozhina A.S., Tregubova A.V., Badlaeva A.S., Lysova N.L., Galagan A.N., Buralkina N.A.
Endometriosis is a chronic estrogen-dependent disease associated with the development of chronic pelvic pain, which significantly affects patients’ quality of life. However, the severity of pain often does not correlate with the extent of lesions or the stage of the disease, suggesting that additional molecular and cellular mechanisms are involved in pain pathogenesis. In recent years, particular attention has been focused on neuroangiogenesis, neuroimmune interactions and pathological innervation of endometriotic lesions as key factors contributing to the development of chronic pain.
The article analyses and summarizes current data on the mechanisms underlying endometriosis-associated pain, with a focus on the role of neuroangiogenesis, neuroimmune inflammation and markers of pathological innervation. This paper examines the characteristics of pain syndrome in various forms of endometriosis, including superficial peritoneal, deep infiltrating and ovarian endometriosis. Special attention is given to the diagnostic and pathogenetic significance of the pan-neuronal marker PGP9.5, the nociceptive sensitization marker TRPV1, the neurotrophin receptor TrkA, and tryptase as a marker of mast cell activation. The article discusses current views on the development of ‘pain phenotype’ of an endometriotic lesion, as determined by the density of innervation, the extent of neurogenesis, the severity of nociceptive sensitization and the activity of the neuroimmune microenvironment. A comprehensive assessment of these markers may help to objectively evaluate pain, stratify patients and develop personalized approaches to the treatment of endometriosis-associated pain.
Conclusion. Endometriosis-associated pain arises as a result of the interaction between neuroangiogenesis, inflammation and sensitization processes. The PGP9.5, TRPV1, TrkA, and tryptase markers reflect key aspects of pain pathogenesis, including innervation of pain foci, neurogenesis, activation of nociceptors and neuroimmune inflammation. The comprehensive assessment of these factors can be used to create an individual pain profile and develop personalized treatment approaches.
Authors’ contributions. Asaturova A.V. – developing the concept, structure and design of the review, writing and editing the text; Tambieva F.R. – search and analysis of literature, writing sections; Rogozhina A.S. – analysis of literature sources, preparation of illustrations; Tregubova A.V. – synthesis of data, formulation of conclusions; Badlaeva A.S. – literature analysis, critical editing; Lysova N.L. – expert assessment of pathological aspects; Galagan A.N. – creation and design of figures and diagrams; Buralkina N.A. – general supervision, approval of the final version.
Conflicts of interest. Authors declare lack of the possible conflicts of interests.
Funding. The research and collection of scientific data for the article were carried out without any sponsorship.
Generative Artificial Intelligence. The Leonardo AI neural network was used to assist in the creation of illustrative material while this article was prepared. The resulting content was checked, edited and approved by the authors. The authors bear full responsibility for the accuracy of the publication’s content.
For citation: Asaturova A.V., Tambieva F.R., Rogozhina A.S., Tregubova A.V., Badlaeva A.S., Lysova N.L., Galagan A.N., Buralkina N.A. Neuroangiogenesis, neuroimmune interactions and markers of pathological innervation
in the development of endometriosis-associated pain. Part I. Biological markers in pain pathogenesis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (8): 30-42 (in Russian)
https://dx.doi.org/10.18565/aig.2026.171
Keywords
endometriosis
chronic pelvic pain
neuroangiogenesis
pathological innervation
pain phenotype
PGP9.5
TRPV1
TrkA
NGF
tryptase
mast cells
neuroimmune interactions
sensitization
neuroinflammation
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Received 02.06.2026
Accepted 14.08.2026
About the Authors
Alexandra V. Asaturova, Dr. Med. Sci., Head of the 1st Pathological Anatomical Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, Associate Professor, Department of Pathological Anatomy andClinical Pathological Anatomy, Institute of Biology and Pathobiology (IBPCh), Pirogov Russian National Research Medical University, Ministry of Health of Russia,
a.asaturova@gmail.com, https://orcid.org/0000-0001-8739-5209
Fatima R. Tambieva, PhD student, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University),
119991, Russia, Moscow, Trubetskaya str., 8, build. 2, dr.inwhite@mail.ru
Aleksandra S. Rogozhina, Junior Researcher, Pathologist, 1st Department of Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, https://orcid.org/0009-0009-6244-1219
Anna V. Tregubova, Pathomorphologist at the 1st Pathoanatomical Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, dr.a.tregubova@gmail.com, https://orcid.org/0000-0003-4601-1330
Alina S. Вadlaeva, Senior Researcher, Pathologist, 1st Department of Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; Associate Professor, Department of Pathological Anatomy and Clinical Pathological Anatomy, Institute of Biology and Pathobiology (IBPCh), Pirogov Russian National Research Medical University, Ministry of Health of Russia,
https://orcid.org/0000-0001-5223-9767
Natalia L. Lysova, PhD, Associate Professor, Department of Pathological Anatomy and Clinical Pathological Anatomy, Pirogov Russian National Research Medical University, Ministry of Health of Russia, 117513, Russia, Moscow, Ostrovityanov str., 1, https://orcid.org/0009-0000-5762-391X
Andrey N. Galagan, Student, Faculty of Medicine, Specialty «General Medicine» (6th year), Russian University of Medicine, Ministry of Health of Russia,
127006, Russia, Moscow, Dolgorukovskaya str., 4, https://orcid.org/0009-0007-0230-5173
Natalya A. Buralkina, Dr. Med. Sci., Senior Researcher at the Department of Surgery, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997, Moscow, Ac. Oparin str., 4, natalyaburalkina@yandex.ru, https://orcid.org/0000-0001-5109-6725
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