Pain pathways and stem cells in endometriosis pathogenesis

As a gynecological disease, endometriosis is a disease in which pain and inflammation are important parts. Endometriosis is a chronic, estrogen-related situation with a multifactorial etiology that remains incompletely understood. Endometriosis affects approximately 6-10% of females and is a prominent reason of infertility. Despite being histologically benign, endometriosis displays invasive behaviors and is associated with systemic inflammatory responses and immune dysfunction. In this text, endometriosis pathogenesis and pain associated with endometriosis is comprehensively explored with particular emphasis on inflammation, pain mechanisms and the emerging role of stem cells. Several theories, including coelomic metaplasia, lymphovascular dissemination, retrograde menstruation, and embryonic rest theory have been recommended to clarify the ectopic location of endometrial tissue. Among these, the immune-mediated inflammatory microenvironment and aberrant neurogenesis are considered in disease progression and the development of pain. The multifactorial nature of endometriosis-associated pain-encompassing inflammatory, neuropathic, and oxidative stress-related mechanisms-highlights the limitations of hormonal treatments and the necessity for new therapeutic perspectives. In this respect, the involvement of stem cells, particularly endometrial and mesenchymal stem cells, has attracted growing interest. These cells are implicated not only in the pathophysiology of the disease but also show promise in regenerative and immunomodulatory therapies. This review aims to present an integrative perspective on endometriosis by examining recent evidence on inflammatory signaling, neuroimmune alterations, and stem cell biology. A deeper understanding of these mechanisms may open new avenues for personalized and multidisciplinary treatment strategies in endometriosis management.