The role of the sympathetic and sensory nervous system in peritoneal endometriotic lesions

Question : The nervous system (NS) has an influence on the pathogenesis of chronic inflammatory autoimmune diseases (AID). The sympathetic NS exerts an anti-inflammatory effect while the sensory NS promotes inflammatory changes, through a stimulation of immune cells and proinflammatory cytokines. A reduced density of sympathetic nerve fibers (syNF) in inflammatory tissue and an increased density of sensory (se) NF could be seen. Similar to AID, endometriosis (EM) is a chronic inflammatory disease, associated with chronic pelvic pain. In human peritoneal endometriotic lesions (pEL), seNF and syNF are present. To study the role of the nervous system in the pain pathogenesis of EM more precise, the sensory and sympathetic innervation in pEL was investigated as well as the expression of Interleukin (IL) 1β and nerve growth factor (NGF) to investigate neuroimmunomodulatory properties and further neurotrophic qualities of EM with an in vitro neuronal model. Methods: pEL and healthy peritoneum specimens were immunostained to investigate the presence of seNF (substance P, SP) and syNF (tyrosin hydroxylase, TH) to determine the ratio of both types of NF. IL 1β and NGF expression was evaluated and correlated with the ratio of seNF and syNF. Sympathetic (syG) and sensory ganglia (seG) were incubated with peritoneal fluids (PF) of patients with peritoneal EM (n=40) and without EM (n=30). Results: In pEL, compared to healthy peritoneum, a significantly increased density of seNF and a significantly lower density of syNF could be detected, revealing an imbalance in pEL (Table 1). This imbalance seems to be influenced by the NGF expression, as specimens with a higher NGF expression reveal a significantly higher ratio of seNF to syNF. IL 1β is significantly overexpressed in pEL, compared to healthy peritoneum. PF of patients with peritoneal EM, compared to the PF of non EM patients, induced a significant higher seNF sprouting in seG. The NF-sprouting of syG was significantly reduced in EM patients compared to non-EM patients (Table 2). Conclusion: As already described in other AID, an imbalance of pro-inflammatory sensory and anti-inflammatory sympathetic innervation in peritoneal EM could be demonstrated. Our data on IL 1β and NGF supports the theory that in EM a neuroimmunomodulation is part of the pathogenesis mechanism. The in vitro model confirmed neuromodulatory properties of the peritoneal fluid of EM patients, as it acts neurotrophic on sensory nerve fibers, but in