Characterizing clinical features and creating a gene expression profile associated with pain burden in children with inflammatory bowel disease

Abstract

Background: There is often dissociation between inflammatory activity and abdominal pain in children with inflammatory bowel disease (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-?? 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.