To investigate the neurotrophic properties of
endometriosis, as well as the involvement of
neurotrophic factors in the development of chronic
pelvic pain in patients with
endometriosis, we performed a prospective clinical study. The presence of
neurotrophins was investigated in the peritoneal fluid (PF) of patients with peritoneal endometriotic lesions or
adenomyosis, as well as from women with non-endometriotic adhesions and from women without
endometriosis/
adenomyosis/adhesions. The PF from patients with peritoneal endometriotic lesions was divided in three groups: asymptomatic
endometriosis, minimal
pain and severe
pain. PF from patients with
adenomyosis or with non-endometriotic adhesions and the control group were divided in patients without
pain and with
pain.
Neurotrophin expression in PF was analyzed using Elisa and the neuronal growth assay with cultured chicken sensory ganglia (dorsal-root-ganglia, DRG) and sympathetic ganglia. PF from women with peritoneal endometriotic lesions overexpress
nerve growth factor (
NGF) and neurotrophin-3 (NT-3), but not
brain derived neurotrophic factor (
BDNF), whereas the PF of women with
adenomyosis or adhesions seems to express normal amounts of these factors.
Neurotrophin expression did not differ among the
pain groups. Furthermore, the PF from patients with peritoneal endometriotic lesions induced a strong sensory and a marginal sympathetic neurite outgrowth, while the PF from women with
adenomyosis and non-endometriotic adhesions induced an outgrowth similar to the control group. The induced neurite outgrowth could only be inhibited in DRG incubated with peritoneal endometriotic lesions. Interestingly, the outgrowth of sympathetic ganglia was inhibited in all studied groups. The present study suggests that only peritoneal endometriotic lesions lead to an increased release of
NGF and NT-3 into the PF and that
NGF modulates the nerve fiber growth in
endometriosis.