Advanced Insights into Human Uterine Innervation: Implications for Endometriosis and Pelvic Pain

(1) Background: Understanding uterine innervation, an essential aspect of female reproductive biology, has often been overlooked. Nevertheless, the complex architecture of uterine innervation plays a significant role in conditions such as endometriosis. Recently, advances in histological techniques have provided unprecedented details about uterine innervation, highlighting its intricate structure, distribution, and density. The intricate nature of uterine innervation and its influence on pathologies such as endometriosis has garnered increasing attention. (2) Objectives: This review aims to compile, analyze, and summarize the existing research on uterine innervation, and investigate its implications for the pathogenesis of endometriosis and associated pain. (3) Methods: A systematic review was conducted in line with PRISMA guidelines. Using the PubMed database, we searched relevant keywords such as "uterine innervation", "endometriosis", and "pain association". (4) Results: The initial literature search yielded a total of 3300 potential studies. Of these, 45 studies met our inclusion criteria and were included in the final review. The analyzed studies consistently demonstrated that the majority of studies focused on macroscopic dissection of uterine innervation for surgical purposes. Fewer studies focused on micro-innervation for uterine innervation. For endometriosis, few studies focused on neural pain pathways whereas many studies underlined an increase in nerve fiber density within ectopic endometrial tissue. This heightened innervation is suggested as a key contributor to the chronic pain experienced by endometriosis patients. (5) Conclusions: The understanding of uterine innervation, and its alterations in endometriosis, offer promising avenues for research and potential treatment.