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It is reported to be a potential trigger for increased postprandial visceral sensitivity in healthy subjects and, especially in patients with irritable bowel syndrome. NR<\/jats:styled-content>2B\u2010containing N<\/jats:italic>\u2010methyl\u2010d<\/jats:sc>\u2010aspartate (NMDA<\/jats:styled-content>) receptors in the central amygdala (CeA) participate in pain modulation. Systemically administered CCK<\/jats:styled-content> activates the CeA\u2010innervating neurons. Here, we investigated whether CCK<\/jats:styled-content> modulation of visceral sensitivity is mediated through CeA NMDA<\/jats:styled-content>\u2010NR<\/jats:styled-content>2B receptors and whether this modulation involves vagal pathway.<\/jats:p><\/jats:sec>Methods<\/jats:title>We first examined the visceromotor response (VMR<\/jats:styled-content>) to colorectal distention (CRD<\/jats:styled-content>) following i.p. injection of CCK<\/jats:styled-content> octapeptide (CCK<\/jats:styled-content>\u20108) in a rat model. Next, the NR<\/jats:styled-content>2B antagonist ifenprodil and the NR<\/jats:styled-content>2A antagonist NVP<\/jats:styled-content>\u2010AAM<\/jats:styled-content>077 were microinjected into the CeA before systemic CCK<\/jats:styled-content> injection. NR<\/jats:styled-content>2B phosphorylation was detected by Western blot. To down\u2010regulate NR<\/jats:styled-content>2B gene expression, NR<\/jats:styled-content>2B\u2010specific small interfering RNA<\/jats:styled-content> (siRNA<\/jats:styled-content>) was delivered into CeA neurons by electroporation. In addition, the effects of functional deafferentation by perivagal application of capsaicin and pretreatment with the CCK<\/jats:styled-content>1<\/jats:sub> receptor antagonist devazepide were investigated.<\/jats:p><\/jats:sec>Key Results<\/jats:title>CCK<\/jats:styled-content>\u20108 increased VMR<\/jats:styled-content> to CRD<\/jats:styled-content> in a dose\u2010dependent manner. This effect was blunted by intra\u2010CeA administration of ifenprodil (but not NVP<\/jats:styled-content>\u2010AAM<\/jats:styled-content>077) and was accompanied by phosphorylation of NR<\/jats:styled-content>2B subunits in the CeA. CCK<\/jats:styled-content> failed to increase VMR<\/jats:styled-content> to CRD<\/jats:styled-content> in NR<\/jats:styled-content>2B siRNA<\/jats:styled-content>\u2010treated rats. Perivagal capsaicin application and pretreatment with devazepide prevented CCK<\/jats:styled-content>\u2010induced pronociception and CeA NR<\/jats:styled-content>2B phosphorylation.<\/jats:p><\/jats:sec>Conclusions & Inferences<\/jats:title>The pronociception induced by systemic CCK<\/jats:styled-content>, which is vagal afferent\u2010dependent, requires activation of CeA NMDA<\/jats:styled-content>\u2010NR<\/jats:styled-content>2B receptors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12633","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T08:33:15Z","timestamp":1437553995000},"page":"1333-1343","source":"Crossref","is-referenced-by-count":15,"title":["Vagal afferent\u2010dependent cholecystokinin modulation of visceral pain requires central amygdala NMDA<\/scp>\u2010NR<\/scp>2B receptors in rats"],"prefix":"10.1111","volume":"27","author":[{"given":"E. M.","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Renji Hospital School of Medicine Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. T.","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Renji Hospital School of Medicine Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. J.","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Renji Hospital School of Medicine Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Renji Hospital School of Medicine Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Renji Hospital School of Medicine Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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