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
{"title":"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","authors":"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","doi":"10.14309/ctg.0000000000000778","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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(RBD).</p><p><strong>Results: </strong>We analyzed 416 IBD patients (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 hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients 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 RBD.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.\",\"authors\":\"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\",\"doi\":\"10.14309/ctg.0000000000000778\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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(RBD).</p><p><strong>Results: </strong>We analyzed 416 IBD patients (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 hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients 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 RBD.</p><p><strong>Discussion: </strong>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.</p>\",\"PeriodicalId\":10278,\"journal\":{\"name\":\"Clinical and Translational Gastroenterology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.14309/ctg.0000000000000778\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14309/ctg.0000000000000778","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.
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(RBD).
Results: We analyzed 416 IBD patients (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 hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients 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 RBD.
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.
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.