Neurotrophins and Their Receptors, Novel Therapeutic Targets for Pelvic Pain in Endometriosis, Are Coordinately Regulated by IL-1β via the JNK Signaling Pathway

Jie Yu, Sarah L Berga, Eric Zou, Andrew D Schrepf, Andrew Schrepf, Daniel J Clauw, Sawsan As-Sanie, Sawsan As‐Sanie, Robert N Taylor
The American journal of pathology · 2023 · vol. 193(8) , pp. 1046–1058 · doi:10.1016/j.ajpath.2023.04.007 · PMID:37164275 · PMC10433690 · W4375851713
article OA: bronze CC0 ⤵ 9 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Interleukin-1 beta coordinately regulates neurotrophins and their receptors, key players in endometriosis-associated pelvic pain, through activation of the JNK signaling pathway.

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Abstract

Pelvic pain in women with endometriosis is attributed to neuroinflammation and afferent nociceptor nerves in ectopic and eutopic endometrium. The hypothesis that uterine nociception is activated by IL-1β, a prominent cytokine in endometriosis, was tested herein. Immunofluorescence histochemistry confirmed the presence of neurons in human endometrial tissue. Expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors in endometrial tissue and cells was validated by immunohistochemistry and Western blotting. Isolated endometrial stromal cells (ESCs) were subjected to dose-response and time-course experiments with IL-1β and kinase inhibitors to characterize in vitro biomarkers. Neural biomarkers were co-localized in endometrial nerve fibers. NGF, BDNF, and their receptors tropomyosin receptor kinase (Trk) A, TrkB, and p75 neurotrophin receptor were all expressed in primary ESCs. IL-1β stimulated higher TrkA/B expression in ESCs derived from endometriosis cases (2.8- ± 0.2-fold) than cells from controls (1.5- ± 0.3-fold, t-test, P < 0.01), effects that were mediated via the c-Jun N-terminal kinase (JNK) pathway. BDNF concentrations trended higher in peritoneal fluid of endometriosis cases but were not statistically different from controls (P = 0.16). The results support the hypothesis that NGF and BDNF and their corresponding receptors orchestrate innervation of the endometrium, which is augmented by IL-1β. We postulate that JNK inhibitors, such as SP600125, have the potential to reduce neuroinflammation in women with endometriosis.

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Condition tags

endometriosischronic_pelvic_pain

MeSH descriptors

Brain-Derived Neurotrophic Factor Brain-Derived Neurotrophic Factor Brain-Derived Neurotrophic Factor Brain-Derived Neurotrophic Factor Brain-Derived Neurotrophic Factor Brain-Derived Neurotrophic Factor Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Biomarkers Biomarkers Biomarkers Biomarkers Biomarkers

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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