Analysis of pain related gene expression in endometriosis and endometriosis related pelvic pain

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Endometriosis is a poorly understood, estradiol-dependent condition associated with severe pelvic pains and defined by vascularized endometrial growths outside the uterus. However, the mechanisms by which pain is generated remain unknown. The broad scope of neurotrophin action is well documented in the case of nerve growth factor (NGF) and its effect on nociceptors and nociception. It was reported that NGF is up-regulated after inflammatory injury and administration of exogenous NGF either systemically or in the skin causes thermal hyperalgesia. We examined NGF, TrkA receptor and p75 receptor expression in the endometriotic lesion and normal endometrium by means of immunohistochemistry, RT-PCR and Western blot. Endometrial cyst wall, adenomyotic lesions, peritoneal endometriotic lesions and normal endometrium were prepared (n=19, 4, 8 and 8, respectively). NGF expression was significantly stronger in peritoneal endometriosis, endometriotic cyst, and adenomotic lesions than in normal endometrium. NGF expression was the most stronger in peritoneal lesions. Although the low affinity neurotrophin receptor (p75NTR) was detected in the endometriotic lesions, high affinity NGF receptor (TrkA) was not detectied in the endometriotic lesions. The levels of NGF in peritoneal fluid were also measured to compare the concentration in women who have endometriosis and in women without endometriosis. NGF was detected in 45% cases. 5 of the 18 control samples (28%) was positive. Of the 46 samples of endometriosis patients, 24 was positive for NGF (52%). These results suggest a role of NGF in the progression of endometriosis. The pain and hyperalgesia in endometriosis may be related with the expression of NGF. The expression of the NGF- p75NTR could explain hyperalgesia in endometriosis.