Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain

Objectives: 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 asso...

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Autores principales: Adam B. Willits, Victoria Grossi, Nicole C. Glidden, Jeffrey S. Hyams, Erin E. Young
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/f271894650fb463e8ebf971d5c41ec8e
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spelling oai:doaj.org-article:f271894650fb463e8ebf971d5c41ec8e2021-11-05T06:51:47ZIdentification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain2673-561X10.3389/fpain.2021.759634https://doaj.org/article/f271894650fb463e8ebf971d5c41ec8e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpain.2021.759634/fullhttps://doaj.org/toc/2673-561XObjectives: 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.Methods: 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-ΔΔ 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 (P ≤ 0.05).Results: 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 (p < 0.001), as well as significantly higher abdominal pain (p = 0.01). Of the 84 genes, expression of GRIN1 (p = 0.02), MAPK3 (p = 0.04), P2X4 (p = 0.04), and PTGES3 (p = 0.02) were all significantly associated with PBI score.Discussion: Abdominal pain associated with IBS/FAP in pediatric patients may be linked to the expression of GRIN1, MAPK3, P2X4, and PTGES3, pointing to potential novel therapeutic targets for management of recurring abdominal pain.Adam B. WillitsVictoria GrossiNicole C. GliddenJeffrey S. HyamsErin E. YoungErin E. YoungErin E. YoungFrontiers Media S.A.articleirritable bowel syndromefunctional abdominal paingene expressionrecurrent abdominal paingenesNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Pain Research, Vol 2 (2021)
institution DOAJ
collection DOAJ
language EN
topic irritable bowel syndrome
functional abdominal pain
gene expression
recurrent abdominal pain
genes
Neurology. Diseases of the nervous system
RC346-429
spellingShingle irritable bowel syndrome
functional abdominal pain
gene expression
recurrent abdominal pain
genes
Neurology. Diseases of the nervous system
RC346-429
Adam B. Willits
Victoria Grossi
Nicole C. Glidden
Jeffrey S. Hyams
Erin E. Young
Erin E. Young
Erin E. Young
Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
description Objectives: 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.Methods: 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-ΔΔ 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 (P ≤ 0.05).Results: 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 (p < 0.001), as well as significantly higher abdominal pain (p = 0.01). Of the 84 genes, expression of GRIN1 (p = 0.02), MAPK3 (p = 0.04), P2X4 (p = 0.04), and PTGES3 (p = 0.02) were all significantly associated with PBI score.Discussion: Abdominal pain associated with IBS/FAP in pediatric patients may be linked to the expression of GRIN1, MAPK3, P2X4, and PTGES3, pointing to potential novel therapeutic targets for management of recurring abdominal pain.
format article
author Adam B. Willits
Victoria Grossi
Nicole C. Glidden
Jeffrey S. Hyams
Erin E. Young
Erin E. Young
Erin E. Young
author_facet Adam B. Willits
Victoria Grossi
Nicole C. Glidden
Jeffrey S. Hyams
Erin E. Young
Erin E. Young
Erin E. Young
author_sort Adam B. Willits
title Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
title_short Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
title_full Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
title_fullStr Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
title_full_unstemmed Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
title_sort identification of a pain-specific gene expression profile for pediatric recurrent abdominal pain
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/f271894650fb463e8ebf971d5c41ec8e
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