{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:01:10Z","timestamp":1789725670236,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2014,10,27]],"date-time":"2014-10-27T00:00:00Z","timestamp":1414368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Health Research Board","award":["HRA_POR\/2010\/52"],"award-info":[{"award-number":["HRA_POR\/2010\/52"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"crossref","award":["07\/CE\/B1368"],"award-info":[{"award-number":["07\/CE\/B1368"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Physiology, UCC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p>Hyperactivity of the stress system and low\u2010grade immune activation characterize the functional bowel disorder irritable bowel syndrome (IBS).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>These studies show that interleukin (IL)\u20106 and IL\u20108 and the stress hormone corticotropin\u2010releasing factor (CRF), present in IBS plasma, have functional effects on gastrointestinal activity by stimulating myenteric neurons and colonic contractions.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Moreover, in the Wistar Kyoto rat model of IBS, which exhibits altered gastrointestinal motility and visceral pain sensitivity, blocking IL\u20106 and\/or CRF1 receptors alleviates these IBS\u2010like symptoms.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Underlying these effects are altered colonic protein expression of tight junction proteins which regulate gut barrier function and the T\u2010type calcium channel Ca<jats:sub>V<\/jats:sub>3.2, which has been linked to visceral pain.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>These findings demonstrate the importance of the enteric nervous system and intestinal physiology in bowel dysfunction.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin\u20106 (IL\u20106) and corticotropin\u2010releasing factor receptor (CRFR) 1 in visceral pain and stress\u2010induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti\u2010IL\u20106 receptor antibodies (xIL\u20106R, 0.5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> <jats:sc>i.p<\/jats:sc>) with or without the CRFR1 antagonist antalarmin (10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> <jats:sc>i.p<\/jats:sc>). Post\u2010intervention, the pain threshold to colorectal distension and stress\u2010induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro\u2010stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL\u20106, IL\u20108 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL\u20106 and CRF1 receptors <jats:italic>in vivo<\/jats:italic> in the WKY IBS rat model normalized stress\u2010induced defecation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and visceral pain sensitivity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain\u2010associated T\u2010type calcium channel Ca<jats:sub>V<\/jats:sub>3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1\/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL\u20106 and CRF1 receptors is effective in alleviating IBS\u2010like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.279968","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T04:15:52Z","timestamp":1411791352000},"page":"5235-5250","source":"Crossref","is-referenced-by-count":63,"title":["Modulation of enteric neurons by interleukin\u20106 and corticotropin\u2010releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome"],"prefix":"10.1113","volume":"592","author":[{"given":"Maria M.","family":"Buckley","sequence":"first","affiliation":[{"name":"Alimentary Pharmabiotic Centre University College Cork  Cork Ireland"},{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken D.","family":"O'Halloran","sequence":"additional","affiliation":[{"name":"Department of 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