Effect of antiangiogenic treatment on peritoneal endometriosis associated nerve fibers

Because nerve fibers present in endometriosis play an important role in pain mechanisms, antiangiogenic treatment that decreases nerve fibers provides a novel therapeutic approach.


Edurne Novella-Maestre, Ph.D., Sonia Herraiz, Ph.D., José María Vila-Vives, M.D., Carmen Carda, Ph.D., M.D., Amparo Ruiz-Sauri, Ph.D., M.D., Antonio Pellicer, Ph.D., M.D.

Vol 98, Issue 5, Pages 1209-1217



To investigate the antiangiogenic treatment effect on experimental endometriotic lesion nerve fibers.


Heterologous mice model of endometriosis.


University Institute IVI, University Hospital La Fe.


Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4).


Endometrium fragments were stuck in the peritoneum of 5-week old female nude mice. Mice were treated with vehicle (n=8) and anti-angiogenic agent Cabergoline (n=8; Cb2, 0.05 mg/kg/day) for 14 days.

Main outcome measure(s):

Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions.


All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls.


Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.

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