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

IF 3 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinical and Translational Gastroenterology Pub Date : 2024-12-01 DOI:10.14309/ctg.0000000000000778

Matthew D Coates, Vonn Walter, August Stuart, Jeffrey Small, Shannon Dalessio, Nurgul Carkaci-Salli, Ann Ouyang, Kofi Clarke, Andrew Tinsley, Emmanuelle D Williams, Piotr Janicki, Victor Ruiz-Velasco, Kent E Vrana

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引用次数: 0

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; 1073 val/val ) related to Na v 1.8, 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 = 0.004) and hypoalgesic UC (32% vs 15%, P = 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n = 50), rs6795970 homozygotes (n = 11) also demonstrated reduced abdominal discomfort to rectal balloon distension.

Discussion: These findings indicate that Na v 1.8 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.

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SCN10A多态性对克罗恩病和溃疡性结肠炎患者腹痛感知和内脏痛觉减退的影响

导读：炎症性肠病（IBD）可能为人类腹痛提供重要的见解。这种情况以前与多态性的纯合性相关(rs6795970, A1073V；1073 val/val)与Na v1.8有关，Na v1.8是一种优先在伤害感受器上表达的电压门控钠通道。目前尚不清楚这种关系是否存在于克罗恩病（CD）和溃疡性结肠炎（UC）。这项研究评估了一个更大的、仔细分型的IBD队列来调查这个问题。方法：比较rs6795970的等位基因和基因型频率在伴有肠道炎症状态和腹痛经历的研究队列中。在健康个体中使用直肠球囊扩张进行内脏感觉知觉。结果：我们分析了416例IBD患者（261CD:155UC）和142例健康对照。在IBD队列中，84人（43CD:41UC）被确定患有疼痛减退症。与其他IBD患者和健康对照相比，低痛觉性IBD患者rs6795970等位基因频率显著升高。与其他IBD患者和健康对照相比，低痛觉性IBD患者也更有可能是这种多态性的纯合子。低痛觉性CD （30% vs 12%, P = 0.004）和低痛觉性UC （32% vs 15%, P = 0.036）与rs6795970多态性的纯合性相关的可能性均显著增加。在一组健康个体（n = 50）中，rs6795970纯合子（n = 11）也表现出直肠球囊膨胀引起的腹部不适减轻。讨论：这些发现表明，Na v 1.8在人类内脏疼痛感知中起着关键作用，可以作为治疗低痛觉性CD和UC的新诊断靶点，以及慢性腹痛相关疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

7.00

自引率

0.00%

发文量

114

审稿时长

16 weeks

期刊介绍： Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.