{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:31:34Z","timestamp":1779906694438,"version":"3.53.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> Functional Abdominal Pain (FAP) and Irritable Bowel Syndrome (IBS) are common recurrent abdominal pain diagnoses with the hallmark, lack of inflammation. To identify a biological signature for IBS\/FAP in the colon, this study used genetic profiling to uncover gene expression changes associated with IBS\/FAP and abdominal pain.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Patients (8 to 17 years) newly diagnosed with IBS or FAP were enrolled in the study. At diagnostic colonoscopy, three rectal biopsies were collected, and gene expression analysis was performed using a Qiagen PCR Array. Relative fold difference in gene expression for 84 pain-associated genes was calculated using the 2-\u0394\u0394 Cq method compared with pain-free controls. Factors affecting pain burden (Pain Burden Interview; PBI) were analyzed, including age, sex, rectal inflammation, and gene expression. Data were analyzed using multiple stepwise linear regression and 2-tailed t tests (<jats:italic>P<\/jats:italic> \u2264 0.05).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Of the 22 total patients in the study, 19 were diagnosed with either IBS-Constipation (frequency of 5.26%), IBS-Diarrhea (47.37%), IBS-Mixed (10.53%), or FAP (36.84%). IBS\/FAP patients reported significantly higher pain burden at the time of diagnosis compared to pain-free controls (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), as well as significantly higher abdominal pain (<jats:italic>p<\/jats:italic> = 0.01). Of the 84 genes, expression of <jats:italic>GRIN1<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.02), <jats:italic>MAPK3<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.04), <jats:italic>P2X4<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.04), and <jats:italic>PTGES3<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.02) were all significantly associated with PBI score.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Abdominal pain associated with IBS\/FAP in pediatric patients may be linked to the expression of <jats:italic>GRIN1, MAPK3, P2X4<\/jats:italic>, and <jats:italic>PTGES3, pointing to potential novel<\/jats:italic> therapeutic targets for management of recurring abdominal pain.<\/jats:p>","DOI":"10.3389\/fpain.2021.759634","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T06:51:52Z","timestamp":1636095112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain"],"prefix":"10.3389","volume":"2","author":[{"given":"Adam B.","family":"Willits","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C.","family":"Glidden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Hyams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1586\/egh.10.28","article-title":"Management of functional abdominal pain and irritable bowel syndrome in children and adolescents","volume":"4","author":"Chiou","year":"2010","journal-title":"Expert Rev Gastroenterol Hepatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1056\/NEJM198403293101305","article-title":"Morbidity in childhood\u2013a longitudinal view","volume":"310","author":"Starfield","year":"1984","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1542\/peds.112.6.1368","article-title":"Importance of parental conceptual model of illness in severe recurrent abdominal pain","volume":"112","author":"Crushell","year":"2003","journal-title":"Pediatrics."},{"key":"B4","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/S0022-3476(96)70246-9","article-title":"Abdominal pain and irritable bowel syndrome in adolescents: a community-based study","volume":"129","author":"Hyams","year":"1996","journal-title":"J Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.jpeds.2008.09.047","article-title":"Prospective school-based study of abdominal pain and other common somatic complaints in children","volume":"154","author":"Saps","year":"2009","journal-title":"J Pediatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cgh.2007.12.019","article-title":"Chronic abdominal pain and depressive symptoms: analysis of the national longitudinal study of adolescent health","volume":"6","author":"Youssef","year":"2008","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1080\/08035250410025104","article-title":"Recurrent abdominal pain: a five-year follow-up study","volume":"94","author":"Stordal","year":"2005","journal-title":"Acta Paediatr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1542\/peds.2005-0114","article-title":"Quality of life for children with functional abdominal pain: a comparison study of patients' and parents' perceptions","volume":"117","author":"Youssef","year":"2006","journal-title":"Pediatrics."},{"key":"B9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.5056\/jnm16214","article-title":"What is new in Rome IV","volume":"23","author":"Schmulson","year":"2017","journal-title":"J Neurogastroenterol Motil."},{"key":"B10","doi-asserted-by":"publisher","first-page":"G1085","DOI":"10.1152\/ajpgi.00542.2011","article-title":"Irritable bowel syndrome: methods, mechanisms, and pathophysiology. 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