{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:53Z","timestamp":1788871913402,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T00:00:00Z","timestamp":1400457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science of China","doi-asserted-by":"crossref","award":["81171041"],"award-info":[{"award-number":["81171041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Natural Science Foundation of Jiangsu Province","award":["BK2011197"],"award-info":[{"award-number":["BK2011197"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (\n IBS<\/jats:styled-content>\n ), its underlying mechanisms remain elusive. Toll\u2010like receptor 4 (\n TLR<\/jats:styled-content>\n 4) is a critical pattern recognition molecule of the innate immune system. In this study, we investigated whether the\n TLR<\/jats:styled-content>\n 4\/myeloid differentiation factor 88 (\n M<\/jats:styled-content>\n y\n D<\/jats:styled-content>\n 88)\/nuclear factor\u2010kappa\n B<\/jats:styled-content>\n (\n NF<\/jats:styled-content>\n \u2010\u03ba\n B<\/jats:styled-content>\n ) signalling pathway in the spinal cord contributed to the visceral hypersensitivity induced by neonatal colonic irritation (\n CI<\/jats:styled-content>\n ) in rats.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The\n S<\/jats:styled-content>\n prague\u2010Dawley rat model of\n IBS<\/jats:styled-content>\n was induced by colon irritation on post\u2010natal day (\n PND<\/jats:styled-content>\n ) 8,\n PND<\/jats:styled-content>\n 10 and\n PND<\/jats:styled-content>\n 12. Experiments were conducted in adult rats.\n TLR<\/jats:styled-content>\n 4 m\n RNA<\/jats:styled-content>\n and protein, and its downstream signalling molecules,\n M<\/jats:styled-content>\n y\n D<\/jats:styled-content>\n 88, inhibitory nuclear factor\u2010kappa\n B<\/jats:styled-content>\n (\n I<\/jats:styled-content>\n \u03ba\n B<\/jats:styled-content>\n ) and\n NF<\/jats:styled-content>\n \u2010\u03ba\n B<\/jats:styled-content>\n protein expressions in\n L<\/jats:styled-content>\n 2\u2010\n S<\/jats:styled-content>\n 4 spinal segments were detected by quantitative real\u2010time reverse transcription\u2010polymerase chain reaction as well as Western blotting.\n TLR<\/jats:styled-content>\n 4 co\u2010localization was determined by immunohistochemistry. Levels of tumour necrosis factor\u2010alpha (\n TNF<\/jats:styled-content>\n \u2010\u03b1) and interleukin 1\u03b2 (\n IL<\/jats:styled-content>\n \u20101\u03b2) were measured with enzyme\u2010linked immunosorbent assay.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found that neonatal\n CI<\/jats:styled-content>\n treatment induced long\u2010lasting visceral hypersensitivity without identifiable structural abnormalities in descending colons of adult rats. Neonatal\n CI<\/jats:styled-content>\n treatment evoked a significant up\u2010regulation of the expressions of\n TLR<\/jats:styled-content>\n 4 in glia,\n M<\/jats:styled-content>\n y\n D<\/jats:styled-content>\n 88, p\u2010\n I<\/jats:styled-content>\n \u03ba\n B<\/jats:styled-content>\n \u2010\u03b1 and\n NF<\/jats:styled-content>\n \u2010\u03ba\n B<\/jats:styled-content>\n in adult rats. Neonatal\n CI<\/jats:styled-content>\n treatment also increased the levels of its downstream inflammatory agents\n TNF<\/jats:styled-content>\n \u2010\u03b1 and\n IL<\/jats:styled-content>\n \u20101\u03b2 in the\n L<\/jats:styled-content>\n 2\u2013\n S<\/jats:styled-content>\n 4 regions of the spinal cord of adult rats.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results suggest that neonatal\n CI<\/jats:styled-content>\n stimulates the production of\n IL<\/jats:styled-content>\n \u20101\u03b2 and\n TNF<\/jats:styled-content>\n \u2010\u03b1 through the\n TLR<\/jats:styled-content>\n 4\/\n M<\/jats:styled-content>\n y\n D<\/jats:styled-content>\n 88\/\n NF<\/jats:styled-content>\n \u2010\u03ba\n B<\/jats:styled-content>\n signalling pathway in the spinal cord, which contributed to visceral hypersensitivity induced by neonatal\n CI<\/jats:styled-content>\n in rats.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ejp.534","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T21:52:54Z","timestamp":1400536374000},"page":"176-186","source":"Crossref","is-referenced-by-count":39,"title":["Spinal toll\u2010like receptor 4\u2010mediated signalling pathway contributes to visceral hypersensitivity induced by neonatal colonic irritation in rats"],"prefix":"10.1002","volume":"19","author":[{"given":"Z\u2010Y.","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical College China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X\u2010W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical College China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Yu","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Anesthesiology 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