Sexual Pain in Endometriosis

Sexual Pain in Endometriosis is associated with increased levels of Nerve Growth Factor and its receptors

Key Points

Highlight:

• Women with endometriosis can experience dyspareunia. The study objective was to investigate the role of nerve growth factor (NGF) in endometriosis-associated dyspareunia.
• NGF and TrkA protein levels were elevated in women with deep dyspareunia.

Importance:

• NGF is a small secreted endocrine regulator for the growth, maintenance, and survival of neurons (nerve cells).
• The level of elevated NGF was associated with deep dyspareunia in women with uterosacral endometriosis.

What's done here:

• The study recruited 32 women with endometriosis in the posterior pelvic compartment (uterosacral or cul-de-sac), either with (17 women) or without (15 women) deep dyspareunia symptoms.
• The expression of NGF and its receptors (TrkA and p75NTR) in surgically excised uterosacral endometriosis was examined by immunohistochemistry.
• Endometriotic stromal cells (ESCs) from endometriosis tissues were cultured and incubated with NGF and Trk inhibitor K252a to evaluate levels of other related inflammatory factors: prostaglandin-endoperoxide synthase 2 (PTGS-2)/cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) secretion.

Data:

• NGF and TrkA, but not p75NTR were significantly elevated in women with deep dyspareunia compared to women without deep dyspareunia.
• NGF immunoreactivity in the endometriotic stroma was significantly associated with deep dyspareunia intensity and local nerve bundle density.
• NGF significantly increased PTGS-2/COX-2 mRNA and protein levels. These effects could be abolished by pretreatment with Trk inhibitor.

Limitations:

• The study did not examine the eutopic (uterine) endometrium for comparison.
• Levels of inflammatory factors in the corresponding endometriosis specimen were not examined in situ.
• Relatively small sample size.

Lay Summary

Pelvic pain during sexual intercourse (deep dyspareunia) is a major concern for women with endometriosis. As many as half of women with endometriosis experience deep dyspareunia and has been shown to have a detrimental impact on quality of life. The mechanism of endometriosis-associated deep dyspareunia is not well understood. However, cul-de-sac/uterosacral (i.e., the cul-de-sac peritoneal fold between the uterus and the rectum) endometriosis is more likely to be associated with deep dyspareunia.

To understand deep dyspareunia, Peng et al. studied NGF in women with endometriosis in the uterosacral or cul-de-sac area. This study published in Reproductive Sciences recruited 32 women with uterosacral/cul-de-sac endometriosis confirmed by endovaginal ultrasound-assisted palpation on examination either with (17 women) or without (15 women) deep dyspareunia symptoms. The expression levels of NGF and its receptors (TrkA and p75NTR) examined in the surgically excised cul-de-sac/uterosacral endometriosis specimens by immunohistochemistry. Also, the endometriotic stromal cells (ESCs) from 3 samples of ectopic endometriosis lesions were cultured and incubated with NGF and Trk inhibitor, K252a. From these cultured cells, the authors analyzed levels of inflammatory factors PTGS-2/COX-2, and prostaglandin E2 (PGE2) secretion. NGF is an important endocrine regulator neuron (nerve cells) growth, maintenance, and survival. It is also known to contribute pain that is associated with other medical conditions such as rheumatoid arthritis and cancer. Hence, it is of significance to understand if there is an association between NGF and endometriosis-associated deep dyspareunia.

The results showed that NGF and TrkA protein levels were elevated in women with deep dyspareunia compared to women without deep dyspareunia. NGF expression in the endometriotic stroma (the surrounding supporting tissue) was correlated with nerve bundle density in endometriotic tissues and the severity of deep dyspareunia. In cultured endometriotic stromal cells, NGF increased COX-2 expression and PGE2 secretion, which can be abolished by pretreatment of Trk inhibitor, K252a. Thus, these data suggested the involvement of NGF in nerve growth and pain in endometriosis

There are several limitations in this study. The authors have focused on uterosacral/cul-de-sac endometriosis and did not have eutopic (uterine) endometrium samples for comparison. It is unclear whether inflammatory factor COX-2 was involved because authors did not examine its level in their specimens. Furthermore, the results from this study would be interpreted with higher confidence given larger sample size number. Nonetheless, this study showed the involvement of NGF which may be targetable for future therapy to reduce deep dyspareunia in women with endometriosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28673205