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Recent studies revealed that acid-sensing ion channels (ASICs) control the excitability of nociceptors in the urinary bladder. Using genetic and pharmacological tools we show that ASICs are functionally coupled with voltage-gated Ca2+ channels to mediate Ca2+ transients evoked by acidification in sensory neurons. Genetic deletion of Asic3 of these sensory neurons does not alter the mechanical response of bladder afferents to distension in na\u00efve mice. Both control and sensory neuron conditional Asic3 knockout (Asic3-KO) mice with chemical cystitis induced by cyclophosphamide (CYP) administration exhibit frequent low volume voiding events. However, these changes are transient and revert over time. Of major significance, in Asic3-KO mice, CYP treatment results in the sensitization of a subset of bladder afferents and pelvic allodynia that persist beyond the resolution of the inflammatory process. Thus, ASICs function is necessary to prevent long-term sensitization of visceral nociceptors.<\/jats:p>","DOI":"10.3390\/ijms252312503","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:46:11Z","timestamp":1732164371000},"page":"12503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expression of Acid-Sensing Ion Channel 3 in Afferents Averts Long-Term Sensitization and the Development of Visceral Pain"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2897-9540","authenticated-orcid":false,"given":"Nicolas","family":"Montalbetti","sequence":"first","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-9193","authenticated-orcid":false,"given":"Guadalupe","family":"Manrique-Maldonado","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-1523","authenticated-orcid":false,"given":"Youko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"},{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Dalghi","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kanai","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"},{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Apodaca","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"},{"name":"Department of Cell Biology, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1901-1618","authenticated-orcid":false,"given":"Marcelo D.","family":"Carattino","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburg, PA 15261, USA"},{"name":"Department of Cell Biology, University of Pittsburgh, Pittsburg, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nm.2235","article-title":"Nociceptor sensitization in pain pathogenesis","volume":"16","author":"Gold","year":"2010","journal-title":"Nat. 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