Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain

PURPOSE: Recent studies have shown that abnormal distribution of pelvic nerves contributes to endometriosis-associated pain. However, the relationship between neurogenesis and pain severity in endometriosis still remains uncertain, which makes it an enigma for both gynecologists as well as neuropathologists. In this study, we tried to explore a special phenomenon, perineural invasion (PNI), in deep infiltrating endometriosis (DIE) and investigated the correlation between PNI- and DIE-associated pain. PATIENTS AND METHODS: The study was conducted in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Sun Yat-sen University from June 2012 to January 2015. In total, 64 patients with DIE were enrolled. They received laparoscopically surgical resection of endometriotic lesions. The Kruskal–Wallis and Mann–Whitney tests were used for comparisons of enumeration data. Spearman rank correlation was used for linear analysis. RESULTS: Immunohistochemical analysis demonstrated that PNI was commonly found in DIE lesions. Patients were divided into PNI (+) group and PNI (−) group. The visual analog scale scores of dysmenorrhea, dyspareunia, and chronic pelvic pain were higher in PNI (+) group than in PNI (−) group. Also, we found significantly increased density of newly formed nerve fibers as well as microvessels in lesions of PNI (+) group. Further, double immunofluorescence showed a closely spatial nerve–vessel network in the endometriotic lesion of PNI (+) group. More importantly, correlation analysis revealed positive relation between the density of newly formed nerve fibers in the lesion and the density of microvessels in lesions of PNI (+) group. CONCLUSION: This study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named “neuroangiogenesis”.