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Published on: April 11, 2018
Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
Adam B Willits1, Victoria Grossi2, Nicole C Glidden3
1Neuroscience Program, KU Medical Center, Kansas City, KS, United States.
Insights
Pediatric patients with functional abdominal pain (FAP) and irritable bowel syndrome (IBS) show distinct gene expression profiles. Specific genes like GRIN1, MAPK3, P2X4, and PTGES3 are linked to pain burden, suggesting new therapeutic targets.
Area of Science:
- Gastroenterology
- Pediatric Medicine
- Molecular Biology
Background:
- Functional Abdominal Pain (FAP) and Irritable Bowel Syndrome (IBS) are prevalent conditions in children characterized by recurrent abdominal pain without inflammation.
- Identifying a biological signature for these conditions is crucial for accurate diagnosis and targeted treatment.
Purpose of the Study:
- To investigate gene expression changes in the colon of pediatric patients diagnosed with IBS or FAP.
- To uncover a potential biological signature associated with IBS/FAP and abdominal pain burden.
Main Methods:
- Gene expression analysis was performed on rectal biopsies from 22 pediatric patients (8-17 years) with newly diagnosed IBS or FAP using a Qiagen PCR Array.
- Expression levels of 84 pain-associated genes were compared to pain-free controls, and factors influencing pain burden were analyzed.
Main Results:
- IBS/FAP patients reported significantly higher pain burden and abdominal pain compared to controls.
- The expression of four genes—GRIN1, MAPK3, P2X4, and PTGES3—was significantly associated with the pain burden score in pediatric IBS/FAP patients.
Conclusions:
- The study identifies a potential genetic link between specific gene expression patterns (GRIN1, MAPK3, P2X4, PTGES3) and abdominal pain in pediatric IBS/FAP.
- These findings suggest novel therapeutic targets for managing recurrent abdominal pain in children.
Abstract:
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.
