{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:58:10Z","timestamp":1785473890023,"version":"3.56.0"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uric acid (UA) is an endogenous antioxidant that protects against neuroinflammatory diseases. Although irritable bowel syndrome (IBS) is considered a disorder of gut\u2013brain interaction, the role of UA in IBS remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An experimental rat model of IBS was induced using laser\u2010induced shock waves (LISW) applied to the head. Hyperuricemia (HUA) was induced by intraperitoneal administration of inosine monophosphate and potassium oxonate. Visceral hypersensitivity was assessed by colorectal distension. Ileal mucosal permeability was measured using the Evans blue method. CRFR1 mRNA expression in the rectum, IL\u201010 and TGF\u2010\u03b21 expression in the ileum, and IL\u20101\u03b1, IL\u20101\u03b2, and TNF expression in the medial prefrontal cortex (mPFC) and paraventricular nucleus (PVN) were quantified by qRT\u2010PCR. Vagal involvement was assessed using subdiaphragmatic vagotomy or atropine treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>LISW increased visceral hypersensitivity, ileal mucosal permeability, and rectal CRFR1 expression and reduced IL\u201010 expression in the ileum. HUA significantly ameliorated these changes. HUA was also associated with reduced IL\u20101\u03b2 expression in the mPFC and reduced IL\u20101\u03b1 and IL\u20101\u03b2 expression in the PVN in LISW\u2010treated animals. Importantly, the ameliorative effects of HUA on visceral hypersensitivity were abolished by vagotomy or atropine treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>Hyperuricemia ameliorated LISW\u2010induced visceral hypersensitivity, improved ileal mucosal permeability, restored IL\u201010 expression in the ileal mucosa, and reduced proinflammatory cytokine expression in the brain. The loss of HUA\u2010induced suppression of visceral hypersensitivity after vagotomy or atropine treatment suggests the possible involvement of vagal and cholinergic brain\u2013gut communication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70396","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:46:41Z","timestamp":1783914401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effect of Uric Acid on Rat Model of Irritable Bowel Syndrome Requires Brain\u2013Gut Communication Through Vagal Cholinergic Pathways"],"prefix":"10.1111","volume":"38","author":[{"given":"Hiroyuki","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of Internal Medicine National Defense Medical College  Saitama 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