{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:08:08Z","timestamp":1793362088846,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670484"],"award-info":[{"award-number":["81670484"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470812"],"award-info":[{"award-number":["81470812"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270463"],"award-info":[{"award-number":["81270463"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500412"],"award-info":[{"award-number":["81500412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Increased colonic bile acid (BA) exposure, frequent in diarrhea\u2010predominant irritable bowel syndrome (IBS\u2010D), can affect gut function. Nerve growth factor (NGF) is implicated in the development of visceral hyper\u2010sensitivity (VH). In this study, we tested the hypothesis that BAs cause VH\n                    <jats:italic>via<\/jats:italic>\n                    mucosal mast cell (MMC)\u2010to\u2010nociceptor signaling, which involves the farnesoid X receptor (FXR)\/NGF\/transient receptor potential vanilloid (TRPV)1 axis. BAs were intracolonically administered to rats for 15 d. Visceral sensitivity to colorectal distention and colonic NGF expression were examined. BAs caused VH, an effect that involved MMC\u2010derived NGF and was accompanied by enhanced TRPV1 expression in the dorsal root ganglia. Anti\u2010NGF treatment and TRPV1 antagonism inhibited BA\u2010induced VH. BAs induced NGF mRNA and protein expression and release in cultured mast cells. Colonic supernatants from patients with IBS\u2010D with elevated colonic BA content transcriptionally induced NGF expression. In\n                    <jats:italic>FXR<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, visceral sensitivity and colonic NGF expression were unaltered after BA treatment. Pharmacological antagonism and FXR silencing suppressed BA\u2010induced NGF expression and release in mast cells. Mitogen\u2010activated protein kinase kinase (MKK) 3\/6\/p38 MAPK\/NF\u2010\u03baB signaling was mechanistically responsible for FXR\u2010mediated NGF expression and secretion. The findings show an MMC\u2010dependent and FXR\u2010mediated pronociceptive effect of BAs and identify the BA\/FXR\/NGF\/TRPV1 axis as a key player in MMC\u2010to\u2010neuron communication during pain processing in IBS.\u2014Li, W.\u2010T., Luo, Q.\u2010Q., Wang, B., Chen, X., Yan, X.\u2010J., Qiu, H.\u2010Y., Chen, S.\u2010L. Bile acids induce visceral hypersensitivity\n                    <jats:italic>via<\/jats:italic>\n                    mucosal mast cell\u2013to\u2013nociceptor signaling that involves the farnesoid X receptor\/nerve growth factor\/transient receptor potential vanilloid 1 axis. FASEB J. 33, 2435\u20132450 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800935rr","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T14:01:21Z","timestamp":1538056881000},"page":"2435-2450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Bile acids induce visceral hypersensitivity\n                    <i>via<\/i>\n                    mucosal mast cell\u2013to\u2013nociceptor signaling that involves the farnesoid X receptor\/nerve growth factor\/transient receptor potential vanilloid 1 axis"],"prefix":"10.1096","volume":"33","author":[{"given":"Wen-Ting","family":"Li","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":"Qing-Qing","family":"Luo","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":"Bo","family":"Wang","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":"Xin","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":"Xiu-Juan","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":"Hong-Yi","family":"Qiu","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":"Sheng-Liang","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"}]}],"member":"311","published-online":{"date-parts":[[2018,9,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.029"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1207068"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.03.035"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521003702734"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.04.020"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13227"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.215"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.11.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12426"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00194.2001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106644"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.015867"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305965"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.08.051"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01489324"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.01.042"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3739"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3249-15.2016"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.05.019"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311456"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1053\/gast.2000.19576","article-title":"Anew model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development","volume":"119","author":"A-Chaer E. 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