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Recent findings revealed a link between cholecystokinin (CCK), neurotrophin synthesis, and intestinal hyperalgesia. The aim was to investigate the role of CCK in visceral hypersensitivity using mouse models challenged with a bout of infection with<jats:italic>Giardia lamblia<\/jats:italic>or psychological stress, either alone or in combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Abdominal pain was evaluated by visceromoter response to colorectal distension. Nerve fibers in intestinal tissues were stained using immunohistochemistry (PGP9.5). Human neuroblastoma SH\u2010SY5Y cells incubated with bacterial\u2010free mouse gut supernatant or recombinant CCK\u20108S were assessed for neurite outgrowth and nerve growth factor (NGF) production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Intestinal hypersensitivity was induced by either stress or<jats:italic>Giardia<\/jats:italic>infection, and a trend of increased pain was seen following dual stimuli. Increased CCK levels and PGP9.5 immunoreactivity were found in colonic mucosa of mice following stress and\/or infection. Inhibitors to the CCK\u2010A receptor (L\u2010364718) or CCK\u2010B receptor (L\u2010365260) blocked visceral hypersensitivity caused by stress, but not when induced by giardiasis. Nerve fiber elongation and NGF synthesis were observed in SH\u2010SY5Y cells after incubation with colonic supernatants from mice given the dual stimuli, or after treatment with CCK\u20108S. Increased nerve fiber length by colonic supernatant and CCK\u20108S was attenuated by L\u2010365260 or neutralizing anti\u2010NGF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>This new model successfully recapitulates intestinal hypernociception induced by stress or<jats:italic>Giardia<\/jats:italic>. Colonic CCK contributes to visceral hypersensitivity caused by stress, but not by<jats:italic>Giardia<\/jats:italic>, partly via NGF\u2010dependent neurite outgrowth.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13296","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T18:13:17Z","timestamp":1452967997000},"page":"1594-1603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Gut\u2010derived cholecystokinin contributes to visceral hypersensitivity via nerve growth factor\u2010dependent neurite outgrowth"],"prefix":"10.1111","volume":"31","author":[{"given":"Luo\u2010Ting","family":"Hsu","sequence":"first","affiliation":[{"name":"Graduate Institute of Physiology National Taiwan University College of Medicine Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan\u2010Yang","family":"Hung","sequence":"additional","affiliation":[{"name":"Graduate Institute 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