Nerve fibres in peritoneal endometriosis

TLDR

Endometriosis is a gynecological disease that can cause severe pelvic pain, yet the mechanisms of pain generation remain unknown. Peritoneal endometriotic lesions, normal peritoneum, and endosalpingiosis lesions from women with and without endometriosis were immunohistochemically stained for PGP9.5, neurofilament, NGF, NGFRp75, substance P, CGRP, acetylcholine, and tyrosine hydroxylase to identify myelinated, unmyelinated, sensory, cholinergic, and adrenergic nerve fibres. Peritoneal endometriotic lesions contained significantly more nerve fibres than normal peritoneum or endosalpingiosis lesions, with SP, CGRP, ACh, and TH immunoreactivity and co‑localization, intense NGF immunoreactivity near glands, and NGFRp75‑positive fibres near glands and vessels, suggesting these fibres may contribute to pain generation.

Abstract

BACKGROUND: Endometriosis is a gynaecological disease that can be associated with severe pelvic pain; however, the mechanisms by which pain is generated remain unknown. METHODS: Peritoneal endometriotic lesions and normal peritoneum were prepared from women with and without endometriosis (n = 40 and 36, respectively). Specimens were also prepared from endosalpingiosis lesions (n = 9). These sections were stained immunohistochemically with antibodies against protein gene product 9.5, neurofilament (NF), nerve growth factor (NGF), NGF receptor p75 (NGFRp75), substance P (SP), calcitonin gene-related peptide (CGRP), acetylcholine (ACh) and tyrosine hydroxylase (TH) to demonstrate myelinated, unmyelinated, sensory, cholinergic and adrenergic nerve fibres. RESULTS: There were significantly more nerve fibres identified in peritoneal endometriotic lesions than in normal peritoneum (P < 0.001) or endosalpingiosis lesions (P < 0.001). These nerve fibres were SP, CGRP, ACh or TH immunoreactive. Many of these markers were co-localized. There was an intense NGF immunoreactivity near endometriotic glands, and NGFRp75 immunoreactive nerve fibres were present near endometriotic glands and blood vessels in the peritoneal endometriotic lesions. CONCLUSIONS: Peritoneal endometriotic lesions were innervated by sensory Aδ, sensory C, cholinergic and adrenergic nerve fibres. These nerve fibres may play an important role in the mechanisms of pain generation in this condition.