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An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity. Male, cynomolgus macaques underwent five four\u2010week treatments of dextran sodium sulfate (DSS)\u2010distilled water (DW), which induced mild\u2013moderate colitis with remission during each treatment cycle. Balloon rectal distention (RD) was performed under anesthesia 14\u2009weeks after the final DSS\u2010DW treatment. Colonoscopy confirmed the absence of colitis prior to the start of RD. In na\u00efve, untreated macaques, 10, 20 and 30\u2009ml RD did not evoke brain activation. However, insular cortex\/somatosensory II cortex and cerebellum were significantly activated in DSS\u2010treated macaques at 20 and 30\u2009ml rectal distention. Intra\u2010rectal pressure after DSS treatment was not significantly different from that of na\u00efve, untreated macaques, indicating lack of alteration of rectal functioning following DSS\u2010treatment. Treatment with 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist alosetron (p.o.) reduced distension\u2010evoked brain activation and decreased intra\u2010rectal pressure. The current findings demonstrated activation of brain regions to RD following DSS treatments which was not present in na\u00efve macaques, suggesting visceral hypersensitivity. Brain activation in turn was reduced by alosetron, which could underlie the analgesic effect alosetron in IBS patients.<\/jats:p>","DOI":"10.1096\/fba.2022-00048","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T01:55:28Z","timestamp":1660787728000},"page":"694-708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome"],"prefix":"10.1096","volume":"4","author":[{"given":"Rintaro","family":"Fujii","sequence":"first","affiliation":[{"name":"Hamamatsu Pharma Research, Inc.  Hamamatsu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Awaga","sequence":"additional","affiliation":[{"name":"Hamamatsu Pharma Research, Inc.  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