Geburtshilfe Frauenheilkd 2011; 71 - A38
DOI: 10.1055/s-0031-1292729

Neurotrophic events in peritoneal endometriotic lesions

ML Barcena de Arellano 1, J Arnold 1, C Rüster 1, GF Vercellino 1, V Chiantera 1, AD Ebert 2, A Schneider 1, S Mechsner 1
  • 1Charité Campus Benjamin Franklin, Endometriose Forschungslabor, Berlin, Germany
  • 2Vivantes Humboldt-Klinikum, Endometriosezentrum Berlin-Brandenburg Stufe III, Berlin, Germany

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 (p<0.0001). The NGF expression in PF of women with AM or AD was similar to the level in the CG (p>0.05). 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 (p<0.05). The BDNF and NT-3 expression did not differ between the AM and AD and the CG (p>0.05). 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 (p<0.01). DRG treated with PF from women with AM or AD showed a similar outgrowth to that from the DRG treated with PF from the CG (p>0.05). The outgrowth of the DRG treated with PF from women with pEM was significant inhibited with anti-NGF (p<0.001). The outgrowth of the DRG treated with PF from women with AM, AD and from the CG was only marginal blocked when treated with anti-NGF (p>0.05).

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.