Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions

OBJECTIVE: To investigate the topographical relationship between nerve fibers and peritoneal endometriotic lesions and to determine the origin of endometriosis-associated nerve fibers. DESIGN: Retrospective nonrandomized study. SETTING: University hospital endometriosis research center. PATIENT(S): Premenopausal women with histologically confirmed endometriosis were selected (n = 73). Peritoneal endometriotic lesions (n = 106) and unaffected peritoneal biopsies from patients without endometriosis (n = 9) were obtained. INTERVENTION(S): Immunohistochemistry was used to study the expression of neurofilament, substance P, smooth muscle actin, von Willebrand factor, growth-associated protein 43, nerve growth factor, and neutrophin-3 in peritoneal endometriotic lesion samples from women with symptomatic endometriosis and in peritoneal samples from women without endometriosis. RESULT(S): Pain-conducting substance-P-positive nerve fibers were found to be directly colocalized with human peritoneal endometriotic lesions in 74.5% of all cases. The endometriosis-associated nerve fibers are accompanied by immature blood vessels within the stroma. Nerve growth factor and neutrophin-3 are expressed by endometriotic cells. Growth-associated protein 43, a marker of neural outgrowth and regeneration, is expressed in endometriosis-associated nerve fibers but not in existing peritoneal nerves. CONCLUSION(S): The data provide the first evidence of direct contact between sensory nerve fibers and peritoneal endometriotic lesions. This implies that the fibers play an important role in the etiology of endometriosis-associated pelvic pain. Moreover, emerging evidence suggests that peritoneal endometriotic cells exhibit neurotrophic properties.