Grossi V^1,2, Hyams JS^1,2, 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

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

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

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

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

5 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.