{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T02:03:26Z","timestamp":1774663406850,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Interstitial Cystitis\/Bladder Pain Syndrome (IC\/BPS) is a chronic and debilitating condition marked by bladder pain, urinary urgency, and frequency.  The pathophysiology of IC\/BPS remains poorly understood, with limited therapeutic options available. The role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its receptor PAC1 in IC\/BPS has not been thoroughly investigated, despite their potential involvement in inflammation and sensory dysfunction. This study aims to examine the expression and functional role of the PACAP\/PAC1 signaling pathway in the pathogenesis of IC\/BPS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bladder tissue samples from IC\/BPS patients and a rat model of cystitis were analyzed to evaluate PACAP and PAC1 expression.  Transcriptomic analysis, immunohistochemistry, and bladder function assays were employed to assess the correlation between PACAP\/PAC1 activation, bladder inflammation, and sensory dysfunction. Additionally, modulation of the PACAP\/PAC1 pathway was tested in rats to determine its effects on bladder inflammation and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrate significant upregulation of PACAP and PAC1 in both human bladder tissues from IC\/BPS patients and in the rat cystitis model.  This upregulation was associated with increased bladder inflammation and sensory dysfunction. Intervention with PACAP\/PAC1 pathway modulation in rats resulted in a marked reduction in bladder inflammation and improvement in bladder function, suggesting the pathway\u2019s pivotal role in disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The findings provide compelling evidence that the PACAP\/PAC1 pathway is involved in the inflammatory and sensory changes observed in IC\/BPS. By targeting this signaling pathway, we may offer a novel therapeutic approach to mitigate the symptoms of IC\/BPS. This study enhances our understanding of the molecular mechanisms driving IC\/BPS and opens avenues for the development of targeted treatments.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1413078","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T06:33:39Z","timestamp":1732775619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PACAP\/PAC1 regulation in cystitis rats: induction of bladder inflammation cascade leading to bladder 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