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Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic\/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation\/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.<\/jats:p>","DOI":"10.1172\/jci.insight.176103","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T12:00:22Z","timestamp":1706184022000},"source":"Crossref","is-referenced-by-count":5,"title":["Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis"],"prefix":"10.1172","volume":"9","author":[{"given":"Amanda","family":"Wolf-Johnston","sequence":"first","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-1523","authenticated-orcid":true,"given":"Youko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of 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