Abstract

Characterizing Clinical Features and Creating a Gene Expression Profile Associated With Pain Burden in Children With Inflammatory Bowel Disease

Grossi V1,2, Hyams JS1,2, Glidden NC3, Knight BE4, Young EE5. Inflamm Bowel Dis. 2019 Oct 18. pii: izz240. doi: 10.1093/ibd/izz240. [Epub ahead of print]

 
     

Author information

Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut, USA.

Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Department of Anesthesiology, University of Kansas School of Medicine, Kansas City, Kansas, USA.

Abstract

BACKGROUND: There is often dissociation between inflammatory activity and abdominal pain in children with inflammatory boweldisease (IBD), suggesting other factors may play a role in the pain experience.

METHODS: Patients (8 to 17 years) newly diagnosed with IBD were enrolled in the ALLAY Study: Assessing Risk Factors for Abdominal Pain in Children with Inflammatory Bowel Disease (NCT02984059). At diagnostic colonoscopy, 3 rectal biopsies were collected, and gene expression analysis was performed using Qiagen RT2 Profiler Neuropathic and Inflammatory Pain 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: Thirty-nine newly diagnosed IBD patients were included (65% male, mean age 12.75 years [SD 2.63], 23 Crohn's disease, 16 ulcerative colitis), along with 3 controls. Mean PBI score was 7.73 (SD 6.4, range 0 to 23) for all patients. Age and sex were not predictive of pain burden, but disease activity score was (P = 0.03). Expression of TRPV3, OPRM1, P2X3, SCN9A, PTGS2, and MAPK14 were associated with PBI score. Subsequent 2-tailed t tests comparing patients with no pain (PBI score ? 2, N = 11) to those with pain (PBI > 2, N = 28) confirmed differential expression of TRPV3, PTGS2, and MAPK14 was in patients with pain (all P < 0.05).

CONCLUSION: Pain burden in newly diagnosed IBD patients may be linked to TRPV3, PTGS2, and MAPK14 expression, suggesting potential therapeutic targets for managing pain in IBD.

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