An Investigation of the Relationship between Pelvic Pain and Density of Nerve Fibers in Peritoneal Lesions of Endometriosis

Abstract

Purpose Endometriosis is a gynecological disease often characterized by severe pelvic pain, including perimenstrual and intermenstrual pain and dyspareunia. Sensory nerve fibers within peritoneal lesions have previously been shown to contribute to generation of pain in endometriosis; however, their association with different types of pelvic pain is currently uncertain. Methods Peritoneal endometriotic lesions (n = 30) were sectioned and stained immunohistochemically with protein gene product 9.5 (PGP 9.5; pan-neuronal marker), neuropeptide Y (NPY; sympathetic), vasoactive intestinal polypeptide (VIP; parasympathetic), substance P (SP; sensory) and nerve growth factor (NGF) to identify nerve fibers and neurotrophin levels. Densities were assessed within stroma of the lesions and in the adjacent peritoneum. Pelvic pain scores were obtained using a visual analogue scale (VAS), and correlation analysis was performed. Results Increased density of nerve fibers was observed within the stroma of lesions. NGF expression was significantly increased in glandular epithelium, compared with stromal regions (p = 0.026) and correlated inversely with menstrual pain scores (p = 0.05). Sympathetic nerve fiber density (NPY) in stroma showed a significant positive correlation with intensity of menstrual pain (p = 0.04). Parasympathetic nerve fiber density (VIP) also showed a strong trend toward a positive correlation with menstrual pain intensity (p = 0.056). Conclusions There is increased neurogenesis in the stromal region. Innervation of lesions correlates to intensity of menstrual pain. NGF in glandular epithelium may promote growth of nerve fibers into the core of lesions; however, the inverse correlation between NGF expression in glandular epithelium and menstrual pain indicates that mechanisms of pain generation in endometriosis are complex.