{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:25:59Z","timestamp":1792718759436,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T00:00:00Z","timestamp":1406246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Supernatants from colonic mucosal biopsies from patients with irritable bowel syndrome (IBS) activate enteric and dorsal root ganglion (DRG) neurons. Based on the discomfort\/pain threshold during rectal distension, IBS patients may be subtyped as normo\u2010 or hypersensitive. However, the link between neuronal activation and visceral sensitivity remains unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>We found that supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons than supernatants from normosensitive IBS patients. The level of activation correlated with the individual discomfort\/pain threshold pressure values. We therefore conclude that mucosal biopsy supernatants have biomarker potential and may, in the future, help to personalize treatment of IBS patients with different visceral sensitivities.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Based on the discomfort\/pain threshold during rectal distension, irritable bowel syndrome (IBS) patients may be subtyped as normo\u2010 or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that visceral sensitivity is linked to the degree of neuronal activation. Normo\u2010 and hypersensitive IBS patients were distinguished by their discomfort\/pain threshold to rectal balloon distension with a barostat. Using potentiometric and Ca<jats:sup>2+<\/jats:sup> dye imaging, we recorded the response of guinea\u2010pig enteric submucous and mouse dorsal root ganglion (DRG) neurons, respectively, to mucosal biopsy supernatants from normosensitive (<jats:italic>n<\/jats:italic>\u00a0=\u00a012 tested in enteric neurons, <jats:italic>n<\/jats:italic>\u00a0=\u00a09 tested in DRG) and hypersensitive IBS patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a09, tested in both types of neurons). In addition, we analysed the association between neuronal activation and individual discomfort\/pain pressure thresholds. The IBS supernatants evoked Ca<jats:sup>2+<\/jats:sup> transients in DRG neurons and spike discharge in submucous neurons. Submucous and DRG neurons showed significantly stronger responses to supernatants from hypersensitive IBS patients as reflected by higher spike frequency or stronger [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transients and proportion of responding neurons correlated significantly with the individual discomfort\/pain thresholds of the IBS patients. Supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons. The level of activation correlated with the individual discomfort\/pain threshold pressure values. These findings support our hypothesis that visceral sensitivity is linked to activation of peripheral neurons by biopsy supernatants.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2014.080036","type":"journal-article","created":{"date-parts":[[2014,6,21]],"date-time":"2014-06-21T04:43:50Z","timestamp":1403325830000},"page":"1299-1311","source":"Crossref","is-referenced-by-count":47,"title":["Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity"],"prefix":"10.1113","volume":"99","author":[{"given":"Sabine","family":"Buhner","sequence":"first","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breg","family":"Braak","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"},{"name":"Department of Physiology Shangdong University  Shangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Maria","family":"Kugler","sequence":"additional","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamira","family":"Klooker","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Wouters","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders University Hospital Gasthuisberg Catholic University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemma","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Vignali","sequence":"additional","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Mazzuoli\u2010Weber","sequence":"additional","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Grundy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Boeckxstaens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center  Amsterdam The Netherlands"},{"name":"Translational Research Center for Gastrointestinal Disorders University Hospital Gasthuisberg Catholic University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schemann","sequence":"additional","affiliation":[{"name":"Human Biology Technische Universit\u00e4t M\u00fcnchen  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03801.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.055"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.039"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2006.00871.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.54"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.139352"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12011"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.07.005"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.06.004"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.02.060"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29255"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.86"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.140210"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/39639"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.4.523"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301856"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.120"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01100.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00153.2011"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.213108"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02524.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.05.078"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.11.022"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01926.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.219550"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.140806"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.07.024"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2005.12.011"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2006.12.004"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.01.040"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052104"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.241"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.371"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00210-0"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.028514"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.06.017"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fexpphysiol.2014.080036","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/expphysiol.2014.080036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T10:00:16Z","timestamp":1695981616000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/expphysiol.2014.080036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,25]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1113\/expphysiol.2014.080036"],"URL":"https:\/\/doi.org\/10.1113\/expphysiol.2014.080036","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,25]]}}}