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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 na\u00efve 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.<\/jats:p>","DOI":"10.1126\/sciimmunol.adi5578","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T18:58:50Z","timestamp":1709319530000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-3123","authenticated-orcid":true,"given":"Byron W.","family":"Hayes","sequence":"first","affiliation":[{"name":"Department of Pathology, Duke University Medical Center, Durham, NC, 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