Nerve Growth Factor Is Associated With Sexual Pain in Women With Endometriosis

Bo Peng, Zhan H, Hong Zhan, Alotaibi F, Fahad Alotaibi, Fahad T. Alotaibi, Ghadeer M Alkusayer, Mohamed A Bedaiwy, Paul J Yong
Reproductive sciences (Thousand Oaks, Calif.) · 2017 · vol. 25(4) , pp. 540–549 · doi:10.1177/1933719117716778 · PMID:28673205 · W2780337009
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-11 ⓘ

Elevated nerve growth factor and its receptor TrkA were found in endometriosis lesions of women with deep dyspareunia, and in cultured cells, NGF increased COX-2 and PGE2.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

The study examined nerve growth factor (NGF) and its receptors (TrkA and p75NTR) in surgically excised cul-de-sac/uterosacral endometriosis from 32 women with endometriosis, comparing those with deep dyspareunia versus those without using immunohistochemistry and Histoscore blinded to pain phenotype. NGF immunointensity and TrkA were significantly elevated in endometriotic stroma and epithelium in women with deep dyspareunia, while p75NTR was not, and NGF in stroma was associated with both deep dyspareunia intensity and local nerve bundle density; however, the receptor and tissue-expression analyses were cross-sectional and based on a relatively small posterior-compartment cohort. In cultured endometriotic stromal cells, NGF increased PTGS-2/COX-2 expression and PGE2 secretion, and these effects were blocked by the Trk inhibitor K252a. This paper is centrally about endometriosis — specifically linking NGF/TrkA signaling and COX-2/PGE2 activity to endometriosis-associated deep dyspareunia.

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Abstract

Endometriosis is present in 1 in 10 reproductive-age women, and half experience deep dyspareunia (pelvic pain with sexual intercourse). Our objective was to investigate nerve growth factor (NGF) and its receptors (TrkA/p75NTR) in endometriosis-associated deep dyspareunia. A total of 32 women with endometriosis in the posterior pelvic compartment (cul-de-sac/uterosacrals) were included, either with (n = 17) or without (n = 15) deep dyspareunia symptoms confirmed by endovaginal ultrasound-assisted palpation on examination. Expression of NGF, TrkA, and p75NTR in the surgically excised cul-de-sac/uterosacral endometriosis was examined by immunohistochemistry and Histoscore blinded to pain phenotypes. Additionally, endometriotic stromal cells (ESCs; n = 3) from ectopic endometriosis lesions were cultured and incubated with/without NGF and/or Trk inhibitor K252a, followed by expression analysis of prostaglandin-endoperoxide synthase 2 (PTGS-2)/cyclooxygenase 2 (COX-2; reverse transcription quantitative real-time polymerase chain reaction and Western blot) and prostaglandin E2 (PGE2) secretion (enzyme-linked immunosorbent assay). We found that the immunointensity of NGF and TrkA, but not p75NTR, was significantly elevated in endometriotic stroma and epithelium from women with deep dyspareunia compared to women without deep dyspareunia. Nerve growth factor immunoreactivity in the stroma was also significantly associated with deep dyspareunia intensity and local nerve bundle density. In cultured ESCs, NGF significantly increased PTGS-2/COX-2 mRNA and protein levels as well as PGE2 secretion, and these effects could be abolished by pretreatment of Trk inhibitor K252a. In conclusion, elevated NGF levels were associated with deep dyspareunia in women with cul-de-sac/uterosacral endometriosis. This association may be mediated by increased nerve bundle density and by COX-2/PGE2 stimulation via Trk receptor. Nerve growth factor signaling may play an important role in endometriosis-associated sexual pain.
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Abstract

Endometriosis is present in 1 in 10 reproductive-age women, and half experience deep dyspareunia (pelvic pain with sexual intercourse). Our objective was to investigate nerve growth factor (NGF) and its receptors (TrkA/p75NTR) in endometriosis-associated deep dyspareunia. A total of 32 women with endometriosis in the posterior pelvic compartment (cul-de-sac/uter-osacrals) were included, either with (n = 17) or without (n = 15) deep dyspareunia symptoms confirmed by endovaginal ultrasound-assisted palpation on examination. Expression of NGF, TrkA, and p75NTR in the surgically excised cul-de-sac/ uterosacral endometriosis was examined by immunohistochemistry and Histoscore blinded to pain phenotypes. Additionally, endometriotic stromal cells (ESCs; n = 3) from ectopic endometriosis lesions were cultured and incubated with/without NGF and/or Trk inhibitor K252a, followed by expression analysis of prostaglandin-endoperoxide synthase 2 (PTGS-2)/cyclooxygenase 2 (COX-2; reverse transcription quantitative real-time polymerase chain reaction and Western blot) and prostaglandin E2 (PGE2) secretion (enzyme-linked immunosorbent assay). We found that the immunointensity of NGF and TrkA, but not p75NTR, was significantly elevated in endometriotic stroma and epithelium from women with deep dyspareunia compared to women without deep dyspareunia. Nerve growth factor immunoreactivity in the stroma was also significantly associated with deep dyspareunia intensity and local nerve bundle density. In cultured ESCs, NGF significantly increased PTGS-2/COX-2 mRNA and protein levels as well as PGE2 secretion, and these effects could be abolished by pretreatment of Trk inhibitor K252a. In conclusion, elevated NGF levels were associated with deep dyspareunia in women with cul-de-sac/uterosacral endometriosis. This association may be mediated by increased nerve bundle density and by COX-2/PGE2 stimulation via Trk receptor. Nerve growth factor signaling may play an important role in endometriosis-associated sexual pain. Similar content being viewed by others

References

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Reprod. Sci. 25, 540–549 (2018). https://doi.org/10.1177/1933719117716778 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719117716778

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Condition tags

dyspareuniaendometriosischronic_pelvic_pain

MeSH descriptors

Dyspareunia Endometriosis Nerve Growth Factor Peritoneal Diseases Receptor, Nerve Growth Factor Receptor, trkA Dyspareunia Dyspareunia Endometriosis Endometriosis Female Humans Nerve Growth Factor Pelvic Pain Pelvic Pain Pelvic Pain Peritoneal Diseases Peritoneal Diseases Receptor, Nerve Growth Factor Receptor, trkA

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