{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:49:50Z","timestamp":1791902990385,"version":"4.3.4"},"reference-count":66,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>\n                    <jats:bold>Background and aims:<\/jats:bold>\n                    Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Patients and methods:<\/jats:bold>\n                    fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0\u200a=\u200anone, 10\u200a=\u200amaximal).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (\u22121.5 (interquartile range \u22122 to \u22121); p\u200a=\u200a0.001) but not in IBS-C (\u22120.7 (\u22121 to 0.5)), IBS-D (\u22120.5 (\u22121.5 to 0.5)), or in all IBS patients (0 (\u22121.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.028514","type":"journal-article","created":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T20:38:06Z","timestamp":1097527086000},"page":"1595-1601","source":"Crossref","is-referenced-by-count":319,"title":["Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls"],"prefix":"10.1136","volume":"53","author":[{"given":"C H","family":"Wilder-Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Lovblad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Redmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Nirkko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2004,10,11]]},"reference":[{"key":"2025121309501159000_53.11.1595.1","unstructured":"Drossman DA, Corazziari E, Talley NJ, et al. The functional gastrointestinal disorders. McLean: Degnon Associates, 2000:355\u2013362."},{"key":"2025121309501159000_53.11.1595.2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01395503"},{"key":"2025121309501159000_53.11.1595.3","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/0016-5085(90)90620-G","volume":"99","year":"1990","journal-title":"Gastroenterology"},{"key":"2025121309501159000_53.11.1595.4","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/S0022-3565(25)38614-3","volume":"268","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"2025121309501159000_53.11.1595.5","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/j.1365-2036.1993.tb00131.x","volume":"7","year":"1993","journal-title":"Aliment Pharmacol Ther"},{"key":"2025121309501159000_53.11.1595.6","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/0016-5085(94)90809-5","volume":"107","year":"1994","journal-title":"Gastroenterology"},{"key":"2025121309501159000_53.11.1595.7","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90267-8"},{"key":"2025121309501159000_53.11.1595.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70219-1"},{"key":"2025121309501159000_53.11.1595.9","doi-asserted-by":"publisher","DOI":"10.1136\/gut.41.4.505"},{"key":"2025121309501159000_53.11.1595.10","doi-asserted-by":"publisher","DOI":"10.1136\/gut.14.2.125"},{"key":"2025121309501159000_53.11.1595.11","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.4.497"},{"key":"2025121309501159000_53.11.1595.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2000.01677.x"},{"key":"2025121309501159000_53.11.1595.13","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0016-5085(94)90086-8","volume":"107","year":"1994","journal-title":"Gastroenterology"},{"key":"2025121309501159000_53.11.1595.14","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1152\/jn.1989.62.5.1028","volume":"62","year":"1989","journal-title":"J Neurophysiol"},{"key":"2025121309501159000_53.11.1595.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0987-7053(00)87263-9"},{"key":"2025121309501159000_53.11.1595.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70220-8"},{"key":"2025121309501159000_53.11.1595.17","doi-asserted-by":"publisher","DOI":"10.1097\/00002508-199709000-00003"},{"key":"2025121309501159000_53.11.1595.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(96)03295-2"},{"key":"2025121309501159000_53.11.1595.19","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg106"},{"key":"2025121309501159000_53.11.1595.20","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/107.4.1095"},{"key":"2025121309501159000_53.11.1595.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00352-3"},{"key":"2025121309501159000_53.11.1595.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00324-X"},{"key":"2025121309501159000_53.11.1595.23","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.37071"},{"key":"2025121309501159000_53.11.1595.24","unstructured":"Coffin B , Sabate J-M, Jian R, et al. Mechanisms of visceral pain in patients with inflammatory bowel disease or irritable bowel syndrome. 10th World Congress of Pain 2002:1539P139."},{"key":"2025121309501159000_53.11.1595.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70170-3"},{"key":"2025121309501159000_53.11.1595.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05545.x"},{"key":"2025121309501159000_53.11.1595.27","first-page":"1143","volume":"45","year":"1999","journal-title":"Gut"},{"key":"2025121309501159000_53.11.1595.28","first-page":"825","volume":"13","year":"2001","journal-title":"Neuroimage"},{"key":"2025121309501159000_53.11.1595.29","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(00)91847-0"},{"key":"2025121309501159000_53.11.1595.30","doi-asserted-by":"publisher","DOI":"10.1162\/jocn.1992.4.4.352"},{"key":"2025121309501159000_53.11.1595.31","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00098-3"},{"key":"2025121309501159000_53.11.1595.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00416-5"},{"key":"2025121309501159000_53.11.1595.33","unstructured":"Fields HL, Basbaum AI. Central nervous system mechanism of pain modulation. In: Wall PD, Melzack R, eds. Textbook of pain, 4th edn. London: Churchill Livingstone, 1999:309\u201329."},{"key":"2025121309501159000_53.11.1595.34","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90036-1"},{"key":"2025121309501159000_53.11.1595.35","first-page":"102","volume":"863","year":"2000","journal-title":"Brain Res"},{"key":"2025121309501159000_53.11.1595.36","first-page":"113","volume":"28","year":"1995","journal-title":"Biol Res"},{"key":"2025121309501159000_53.11.1595.37","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90355-8"},{"key":"2025121309501159000_53.11.1595.38","doi-asserted-by":"crossref","unstructured":"Dubner R , Ren K. Endogenous mechanisms of sensory modulation. Pain 1999; (suppl 6) :45\u201353.","DOI":"10.1016\/S0304-3959(99)00137-2"},{"key":"2025121309501159000_53.11.1595.39","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90395-6"},{"key":"2025121309501159000_53.11.1595.40","first-page":"291","volume":"33","year":"1999","journal-title":"Curr Rev Pain"},{"key":"2025121309501159000_53.11.1595.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00400-1"},{"key":"2025121309501159000_53.11.1595.42","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1523\/JNEUROSCI.14-07-04095.1994","volume":"14","year":"1994","journal-title":"J Neurosci"},{"key":"2025121309501159000_53.11.1595.43","unstructured":"Jones EG. Perception of visceral sensation. Advances in psychophysiology, vol 5. New York: Jessica Kingsley Publishers, 1994:55\u2013192."},{"key":"2025121309501159000_53.11.1595.44","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1152\/jn.1994.71.2.802","volume":"71","year":"1994","journal-title":"J Neurophysiol"},{"key":"2025121309501159000_53.11.1595.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.2003220"},{"key":"2025121309501159000_53.11.1595.46","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00184-5"},{"key":"2025121309501159000_53.11.1595.47","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s11916-999-0044-7","volume":"3","year":"1999","journal-title":"Curr Rev Pain"},{"key":"2025121309501159000_53.11.1595.48","first-page":"3836","volume":"120","year":"2001","journal-title":"Gastroenterology"},{"key":"2025121309501159000_53.11.1595.49","first-page":"467","volume":"6","year":"2000","journal-title":"Curr Rev Pain"},{"key":"2025121309501159000_53.11.1595.50","unstructured":"Pandya DN. Association cortex. In: Adelman G, Smith B, eds. Encyclopedia of neuroscience on CD-ROM, 2nd edn. Amsterdam: Elsevier Science, 2001."},{"key":"2025121309501159000_53.11.1595.51","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf024"},{"key":"2025121309501159000_53.11.1595.52","first-page":"A137","volume":"118","year":"2000","journal-title":"Gastroenterology"},{"key":"2025121309501159000_53.11.1595.53","doi-asserted-by":"publisher","DOI":"10.1038\/386824a0"},{"key":"2025121309501159000_53.11.1595.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00467-5"},{"key":"2025121309501159000_53.11.1595.55","first-page":"970","volume":"1","year":"2002","journal-title":"J Neurosci"},{"key":"2025121309501159000_53.11.1595.56","doi-asserted-by":"publisher","DOI":"10.1016\/S1364-6613(98)01265-0"},{"key":"2025121309501159000_53.11.1595.57","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91835-5"},{"key":"2025121309501159000_53.11.1595.58","unstructured":"LeDoux JE. Emotional circuits in the brain. In: Adelman G, Smith B, eds. Encyclopedia of neuroscience on CD-ROM, 2nd edn. Amsterdam: Elsevier Science, 2001."},{"key":"2025121309501159000_53.11.1595.59","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.6.861"},{"key":"2025121309501159000_53.11.1595.60","doi-asserted-by":"crossref","first-page":"9896","DOI":"10.1523\/JNEUROSCI.21-24-09896.2001","volume":"21","year":"2001","journal-title":"J Neurosci"},{"key":"2025121309501159000_53.11.1595.61","doi-asserted-by":"crossref","first-page":"7438","DOI":"10.1523\/JNEUROSCI.20-19-07438.2000","volume":"20","year":"2000","journal-title":"J Neurosci"},{"key":"2025121309501159000_53.11.1595.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00316-5"},{"key":"2025121309501159000_53.11.1595.63","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s11916-000-0072-9","volume":"4","year":"2000","journal-title":"Curr Rev Pain"},{"key":"2025121309501159000_53.11.1595.64","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1152\/jn.1997.78.1.521","volume":"78","year":"1997","journal-title":"J Neurophysiol"},{"key":"2025121309501159000_53.11.1595.65","unstructured":"Swanson WL. The limbic system. In: Adelman G, Smith B, eds. Encyclopedia of neuroscience on CD-ROM, 2nd edn. Amsterdam: Elsevier Science, 2001."},{"key":"2025121309501159000_53.11.1595.66","first-page":"A90","volume":"52","year":"2003","journal-title":"Gut"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.2003.028514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T17:50:22Z","timestamp":1765648222000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.2003.028514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,11]]},"references-count":66,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2004,10,11]]},"published-print":{"date-parts":[[2004,11]]}},"alternative-id":["10.1136\/gut.2003.028514"],"URL":"https:\/\/doi.org\/10.1136\/gut.2003.028514","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,11]]}}}