Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn’s Disease and Ulcerative Colitis

Abstract

INTRODUCTION: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn’s disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question. METHODS: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension. RESULTS: We analyzed 416 patients with IBD (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in patients with hypoalgesic IBD when compared with other patients with IBD and healthy controls. Patients with hypoalgesic IBD were also more likely to be homozygous for this polymorphism when compared with other patients with IBD and healthy controls. Hypoalgesic CD (30% vs 12%, P 5 0.004) and hypoalgesic UC (32% vs 15%, P 5 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n 5 50), rs6795970 homozygotes (n 5 11) also demonstrated reduced abdominal discomfort to rectal balloon distension. DISCUSSION: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.