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

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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.

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Authors and Affiliations

  1. Department of Obstetrics & Gynaecology, BC Women’s Centre for Pelvic Pain and Endometriosis, The University of British Columbia, Vancouver, British Columbia, Canada, V6H 3N1

    Bo Peng PhD, Hong Zhan PhD MD, Fahad Alotaibi MSc, Mohamed A. Bedaiwy MD, PhD & Paul J. Yong MD, PhD

  2. Child & Family Research Institute, Vancouver, British Columbia, Canada

    Bo Peng PhD, Hong Zhan PhD MD, Fahad Alotaibi MSc, Mohamed A. Bedaiwy MD, PhD & Paul J. Yong MD, PhD

  3. Department of Clinical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia

    Ghadeer M. Alkusayer MD, MSc

  4. BC Women’s Centre for Pelvic Pain and Endometriosis, Vancouver, British Columbia, Canada

    Mohamed A. Bedaiwy MD, PhD & Paul J. Yong MD, PhD

Authors
  1. Bo Peng PhD
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  2. Hong Zhan PhD MD
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  3. Fahad Alotaibi MSc
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  4. Ghadeer M. Alkusayer MD, MSc
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  5. Mohamed A. Bedaiwy MD, PhD
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  6. Paul J. Yong MD, PhD
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Corresponding author

Correspondence to Paul J. Yong MD, PhD.

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Peng, B., Zhan, H., Alotaibi, F. et al. Nerve Growth Factor Is Associated With Sexual Pain in Women With Endometriosis. Reprod. Sci. 25, 540–549 (2018). https://doi.org/10.1177/1933719117716778

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