{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:29:24Z","timestamp":1791962964403,"version":"4.3.4"},"reference-count":92,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The endocannabinoid (eCB) system includes ligands (anandamide and 2\u2010arachidonoyl glycerol, 2\u2010AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress\u2010related model of visceral hypersensitivity induced by the selective corticotropin\u2010releasing factor receptor subtype 1 (CRF<jats:sub>1<\/jats:sub>) agonist, cortagine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Sprague\u2013Dawley rats were injected subcutaneously (SC) with URB597 (3\u2009mg\/kg) or vehicle and 2\u2009h later, intraperitoneally with cortagine (10\u2009\u03bcg\/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15\u2009min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and na\u00efve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl\u2010ethanolamide, AEA), oleoyl\u2010ethanolamide (OEA) and palmitoyl\u2010ethanolamide (PEA)], and 2\u2010AG. In separate animals, defecation\/diarrhea were monitored after URB597 and cortagine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>URB597 inhibited cortagine\u2010induced increased VMR at 40\u2009mmHg (89.0\u2009\u00b1\u200914.8% vs. 132.5\u2009\u00b1\u200915.6% for vehicle SC, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and 60\u2009mmHg (107.5\u2009\u00b1\u200916.1% vs. 176.9\u2009\u00b1\u200924.4% for vehicle SC, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2\u2010AG did not change. URB597 did not modify cortagine\u2010induced defecation\/diarrhea versus vehicle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF<jats:sub>1<\/jats:sub> signaling supporting a potential strategy of FAAH inhibitors to alleviate stress\u2010related visceral hypersensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14927","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T09:59:50Z","timestamp":1727690390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>FAAH<\/scp> inhibitor <scp>URB597<\/scp> shows anti\u2010hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of <scp>CRF<sub>1<\/sub><\/scp> agonist mediated visceral hypersensitivity in male rats"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-3675","authenticated-orcid":false,"given":"Muriel","family":"Larauche","sequence":"first","affiliation":[{"name":"Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine David Geffen School of Medicine, University of California Los Angeles  Los Angeles California USA"},{"name":"VA Greater Los Angeles Healthcare System  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-8393","authenticated-orcid":false,"given":"Agata","family":"Mulak","sequence":"additional","affiliation":[{"name":"Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine David Geffen School of Medicine, University of California Los Angeles  Los Angeles California USA"},{"name":"VA Greater Los Angeles Healthcare System  Los Angeles California 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