Nerve Pathway Identified That May Mitigate Pain from Endometriosis Interview with:
Robert N. Taylor, MD PhD
Professor of Obstetrics and Gynecology
Investigator, Clinical and Translational Research Center
Jacobs School of Medicine and Biomedical Sciences
University at Buffalo What is the background for this study?

Response: Our laboratory has been interested in the hormonal modulation of endometriosis-associated pain for decades. This disease and its manifestations are multifactorial. In the current study we focused on the role of nerve growth factors and their receptors, interactive proteins that direct the growth of new nerves and allow their circuits to communicate to regions of the brain that sense pain. What should readers take away from your report?

Response: The salient finding in our recent report is that inflammatory cytokine proteins (in our case we selected IL-1 beta as a prototype) that are mediators of immune responses, predominantly activate a selective biochemical pathway: the so-called c-Jun N-terminal kinase (JNK) pathway. A surprising observation was that nerve growth factors and specific receptors were both stimulated via this same biochemical cascade.

The take away concept here is that interference with JNK signaling has the theoretical capacity to both block nerve migration into endometrial tissue and also to block transmission of painful stimuli from endometrial and endometriosis nerves to the brain. Drugs that inhibit the JNK pathway, thus have the potential to mitigate endometriosis-associated pain through non-hormonal mechanisms. Currently approved drugs for the treatment of endometriosis pain target hormone production and are commonly accompanied by side-effects akin to menopausal symptoms. What recommendations do you have for future research as a result of this study?

Response: The current study reflects an in vitro laboratory model of endometriosis created with isolated, purified human cells. More complex surrogates, such as human “organoids” or induced mouse or rat models, will be needed to more closely represent the multicellular lesions that form the disease in women, so that new therapeutic interventions can be more rigorously tested. The latter, we hope, will lead to clinical trials that might prove safe and effective for the millions of women who experience these symptoms. 

Disclosures: The authors of this study have served as consultants to pharmaceutical companies in the past, but have no current conflicts of interest involving the targets identified in the present research.


Yu J, Berga SL, Zou E, Schrepf AD, Clauw DJ, As-Sanie S, Taylor RN. Neurotrophins and Their Receptors, Novel Therapeutic Targets for Pelvic Pain in Endometriosis, Are Coordinately Regulated by IL-1β via the JNK Signaling Pathway. Am J Pathol. 2023 Aug;193(8):1046-1058. doi: 10.1016/j.ajpath.2023.04.007. Epub 2023 May 8. PMID: 37164275.

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Last Updated on August 14, 2023 by