ArticleJournal of advanced research2025
Targeting NGF but not VEGFR1 or BDNF signaling reduces endometriosis-associated pain in mice.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Modulation of Female Reproductive Functions through Nerve Growth Factor: A Systematic Review.Expert reviews in molecular medicine · 2026Pooled it
- WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Homologous): homologous rodent models.Molecular human reproduction · 2025Pooled it
- Phytochemicals Modulating Receptor Tyrosine Kinase Signaling Networks in Endometriosis.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Human biomarker navigator.iMeta · 2026Review
- Hormonal Dysregulation and Neuroinflammation in Endometriosis: Convergent Druggable Pathways.Current issues in molecular biology · 2026Review
- A Narrative Review of Recent Insights on Nerve Growth Factor Signaling in Physiological and Pathological Ovarian Processes in Mammals.Biomolecules · 2026Review
- Lesion size reduction in mouse model of endometriosis following clove (International journal of reproductive biomedicine · 2026Article
- Behavioral attenuation of marble burying and digging mirrors evoked and non-evoked phenotypes in the endometriosis mouse model.Scientific reports · 2026Article
- Neuroendocrine-Immune Axis in Endometriosis: A Review on How the Nervous System Goes Beyond Pain Perception.Biomolecules · 2025Review
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility.International journal of molecular sciences · 2025Review
- Pathogenic Crosstalk Between the Peripheral and Central Nervous System in Rheumatic Diseases: Emerging Evidence and Clinical Implications.International journal of molecular sciences · 2025Review
- Neuroinflammation is responsible for pain in endometriosis - targeting the JAK-STAT pathway and mast cell activation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionEndometriosis is a chronic inflammatory disease that affects ∼10 % of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and angiogenesis.
objectivesWe aim to evaluate the potential for key tyrosine-kinase-receptor-coupled neurotrophic molecules to contribute to endometriosis-associated pain in mice.
methodsPeritoneal fluid was collected from endometriosis patients undergoing surgery and the levels of NGF and VEGFR1 regulators (VEGFA, VEGFB, PLGF, and sVEGFR1) were quantified by ELISA. VEGFR1 regulator concentrations were used to calculate VEGFR1 occupancy. We used genetic depletion, neutralizing antibodies, and pharmacological approaches to specifically block neurotrophic ligands (NGF or BDNF) or receptors (VEGFR1, TRKs) in a murine model of endometriosis-associated pain. Endometriosis-associated pain was measured using von Frey filaments, quantification of spontaneous abdominal pain-related behavior, and thermal discomfort. Disease parameters were evaluated by lesion size and prevalence. To evaluate potential toxicity, we measured the effect of entrectinib dose and schedule on body weight, liver and kidney function, and bone structure (via micro-CT).
resultsWe found that entrectinib (pan-Trk inhibitor) or anti-NGF treatments reduced evoked pain, spontaneous pain, and thermal discomfort. In contrast, even though calculated receptor occupancy revealed that VEGFR1 agonist levels are sufficient to support signaling, blocking VEGFR1 via antibody or tamoxifen-induced knockout did not reduce pain or lesion size in mice. Targeting BDNF-TrkB with an anti-BDNF antibody also proved ineffective. Notably, changing dosing schedule to once weekly eliminated entrectinib-induced bone-loss without decreasing efficacy against pain.
conclusionsThis suggests NGF-TrkA signaling, but not BDNF-TrkB or VEGF-VEGFR1, mediates endometriosis-associated pain. Moreover, entrectinib blocks endometriosis-associated pain and reduces lesion sizes. Our results also indicated that entrectinib-like molecules are promising candidates for endometriosis treatment.
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