Nerve fibre infiltration and expression in peritoneal lesions of endometriosis in a nonhuman primate model of endometriosis

Abstract

Baboon ( Papio anubis) models of endometriosis are thought to mimic the early stages of spontaneous human peritoneal endometriotic disease. The objective of this study was to investigate the presence and course of nerve fibre ingrowth during peritoneal lesion formation in specimens collected at 3 months (early stage of lesion development) and 15 months (late stage of lesion development) after disease initiation compared to pelvic peritoneum (control). Five-micron sections of paraffin-embedded peritoneal lesions were obtained from normally cycling baboons with 3-month (n = 12), 15-month (n = 12) induced endometriosis and pelvic peritoneum (n = 10) from baboons with no endometriosis. Immunohistochemical staining was performed with specific antibodies: protein gene product 9.5 – broad marker of nerve fibres and neurones, neuropeptide Y – sympathetic neurones, substance P – sensory neurones, vasoactive intestinal peptide – parasympathetic neurones, nerve growth factor – development of new neurones and high-affinity receptor for nerve growth factor (tropomyosin receptor kinase A) – neuronal differential. Significantly, more nerve fibres were identified in peritoneal endometriotic lesions collected 15 months after the initiation of experimental protocols compared with 3-month and control samples (p < 0.001). Nerve fibres were immunoreactive for all the tested markers – protein gene product 9.5, neuropeptide Y, substance P, vasoactive intestinal peptide, nerve growth factor and tropomyosin receptor kinase A – indicating the presence of different types of nerve fibres. In conclusion, peritoneal lesions of endometriosis in a nonhuman primate model of endometriosis were found to be progressively and spontaneously innervated by both myelinated and unmyelinated sensory nerve fibres, parasympathetic and sympathetic neurones. These nerve fibres may play an important role in the mechanisms of pain generation in this condition.