Neurotrophic events in peritoneal endometriotic lesions

ML Barcena de Arellano, Julia T. Arnold, C Rüster, GF Vercellino, Vito Chiàntera, AD Ebert, A Schneider, Sylvia Mechsner
In: Geburtshilfe und Frauenheilkunde · 2011 · vol. 71(10) · doi:10.1055/s-0031-1292729 · W2315536164
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This study investigated neurotrophic factors and nerve fibers in peritoneal endometriotic lesions and found a strong NGF expression in the peritoneal fluid of endometriosis patients.

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This study analyzed peritoneal fluid from women with peritoneal endometriotic lesions, adenomyosis, adhesions, and healthy controls to assess neurotrophic factor expression. Using western blotting and neuronal growth assays, researchers found that nerve growth factor (NGF) was significantly overexpressed in the peritoneal fluid of patients with peritoneal endometriosis compared to all other groups. The results demonstrated that this elevated NGF directly stimulated sensory nerve outgrowth, an effect that was inhibited by anti-NGF treatment, whereas adenomyosis and adhesion fluids did not show similar neurotrophic activity. This paper is centrally about endometriosis — specifically investigating the role of neurotrophic factors like NGF in the pathophysiology of peritoneal endometriotic lesions.

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Abstract

Introduction: The development of endometriosis (EM) associated pain seems to be strongly influenced by the incidence of nerve fibers (NF) in close contact to the endometriotic lesions. NF as well as neurotrophins (NT) are found closely to peritoneal endometriotic lesions (pEL). In addition, a strong NGF expression could be achieved in the peritoneal fluid (PF) of patients with EM. EM-associated neuromodulatory effects seem to be due to a complex interaction by several factors. The pain pathomechanisms of EM are not well understood; therefore, a further characterisation of neurotrophic properties of EM is urgently needed.
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Introduction

The development of endometriosis (EM) associated pain seems to be strongly influenced by the incidence of nerve fibers (NF) in close contact to the endometriotic lesions. NF as well as neurotrophins (NT) are found closely to peritoneal endometriotic lesions (pEL). In addition, a strong NGF expression could be achieved in the peritoneal fluid (PF) of patients with EM. EM-associated neuromodulatory effects seem to be due to a complex interaction by several factors. The pain pathomechanisms of EM are not well understood; therefore, a further characterisation of neurotrophic properties of EM is urgently needed. We investigated the expression of NGF, brain derived neurotrophic factor (BDNF) and NT-3 in the PF of patients with pEM, with adenomyosis (AM) or with adhesions (AD) using the neuronal growth assay (NGA) and western blot (WB), to study the role of pEL in neuromodulatory processes,

Methods

Using WB, the expression of NGF, BDNF and NT-3 was analysed in the PF of women with only pEL (n=65), with AM without pEM (n=15), with AD (without EM or AM) (n=11), and of women without EM and AM (CG) (n=30). Chicken sensory ganglia (SG) were treated with PF from women with pEM (n=30), with AM (n=15), with AD (n=11) and from CG (n=30). In addition NGF inhibitors were used to block the neurite outgrowth.

Results

In the PF of women with pEM, NGF is about 12 times overexpressed compared to AM, AD or CG (p0.05). The level of BDNF and NT-3 was 3 times up-regulated in PF of women with pEM compared to the PF-level of women with AM, AD or CG (p0.05). DRG treated with PF from women with pEM showed a significant stronger outgrowth as the DRG treated with PF from women with AM, AD or from the CG (p0.05). The outgrowth of the DRG treated with PF from women with pEM was significant inhibited with anti-NGF (p0.05).

Conclusion

PF of patients with peritoneal EM might exhibit neurotrophic properties. NT expression was significantly higher in the PF of patients with pEL, whereas the NT expression in patients with AM (without pEM) or only AD was similar to the CG, suggesting alterations in the pelvic milieu, which seems to be regulated through the pEL. We could demonstrate that NGF seems to be one of the main factors involved in the outgrowth of sensory nerves in pEM, while the sprouting in AM or AD seems to be NGF-independent. Our data support the theory of neuropathic properties of the pEM as well as that NGF plays a key role in this disease.

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endometriosis

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