ArticleScience immunology2024
Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.
Article in Science immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Potential Efficacy of Polyphenols and Isothiocyanates in the Management of Genitourinary Diseases: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2026Pooled it
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Review
- Bladder mucosal afferents detect UTI and aid pathogen clearance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mesenchymal stromal cell therapy is a long-term regenerative approach for chronic radiation cystitis, involving coordinated modulation of the urothelial, immune, vascular, and fibrotic pathways.Stem cell research & therapy · 2026Article
- Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections.Research square · 2026Article
- Obesity promotes urinary tract infection by disrupting bladder focal adhesion kinase signaling.iScience · 2025Article
- Article
- Ectopic Nociceptor Sprouting as a Key Peripheral Driver of Pain in Rheumatoid Arthritis.Current rheumatology reports · 2025Review
- Benzyl Benzoate Isolation fromPharmaceuticals (Basel, Switzerland) · 2025Article
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Peripheral Mechanisms Underlying Bacillus Calmette-Guerin-Induced Lower Urinary Tract Symptoms (LUTS).Brain sciences · 2024Review
- Persistent Elevation in Urinary Neutrophil Gelatinase-Associated Lipocalin Levels Can Be a Predictor of Urinary Tract Infection Recurrence or Persistence in Women.International journal of molecular sciences · 2024Article
- Setting the tone: nociceptors as conductors of immune responses.Trends in immunology · 2024Review
- Mast cell-sensory neuron crosstalk in allergic diseases.The Journal of allergy and clinical immunology · 2024Review
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI. We noticed a notable increase in neuropeptide content in the lamina propria and indications of enhanced nociceptive activity. In mice subjected to rUTI, we observed sensory nerve sprouting that was associated with nerve growth factor (NGF) produced by recruited monocytes and tissue-resident mast cells. Treatment of rUTI mice with an NGF-neutralizing antibody prevented sprouting and alleviated pelvic sensitivity, whereas instillation of native NGF into naïve mice bladders mimicked nerve sprouting and pain behavior. Nerve activation, pain, and urinary frequency were each linked to the presence of proximal mast cells, because mast cell deficiency or treatment with antagonists against receptors of several direct or indirect mast cell products was each effective therapeutically. Thus, our findings suggest that NGF-driven sensory sprouting in the bladder coupled with chronic mast cell activation represents an underlying mechanism driving bacteria-independent pain and voiding defects experienced by patients with rUTI.
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Registered trials
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