Influence of Somatization on Central Pain Responses in Irritable Bowel Syndrome

躯体化对肠易激综合征中枢疼痛反应的影响

• 批准号: 8261123
• 负责人: GREGORY S SAYUK
• 金额: $ 16.74万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8261123
• 关键词: Abdominal Pain; Affect; Affective; Aftercare; Amitriptyline; Antidepressive Agents; Brain; Brain region; Cerebrum; Clinical; Cognitive; Comorbidity; Data; Development; Diagnosis; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Heterogeneity; Individual; Intestines; Investigation; Irritable Bowel Syndrome; Measures; Medical History; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; National Institute of Diabetes and Digestive and Kidney Diseases; Neuraxis; Neuroanatomy; Outcome; Pain; Pain Disorder; Patients; Pattern; Peripheral; Process; Research; Research Personnel; Role; Rome; Sensory; Series; Signal Transduction; Stimulus; Subgroup; Symptoms; Syndrome; Training; Variant; Visceral; base; career; career development; central pain; experience; instrument; interest; multidisciplinary; neuroimaging; programs; public health relevance; rectal; response; treatment response

DESCRIPTION (provided by applicant): An NIDDK K23 Mentored Patient-Oriented Research Career Development Award is requested to provide support for Gregory S. Sayuk, MD, MPH to continue a rigorous program of mentored methodologic training and investigation into the pathophysiologic role of the central nervous system in irritable bowel syndrome (IBS). IBS is a common abdominal pain disorder, affecting up to one in five individuals. Our limited appreciation for the mechanisms underlying IBS has resulted in a lack of targeted IBS therapies. Though in the past, studies evaluating the mechanistic basis of IBS have focused on bowel-specific factors, more recently evidence has emerged to suggest a potential role of abnormal brain responses to peripheral pain signals in the development of IBS. Of particular interest to the investigator is the overlap of IBS with somatization, a condition characterized by multiple unexplained pain comorbidities. Present in one-third of IBS subjects, somatization results in poor IBS clinical outcomes. The overall goals of the applicant's research are: (1) to elucidate the mechanisms by which somatization influences brain responses to peripheral pain signals in IBS, and (2) to determine whether these differences in CNS responses based on the presence of somatization are relevant to IBS symptom experiences. The proposed investigations are a logical extension of the preliminary data which provided initial evidence of a unique IBS-somatization pattern of brain activations within the homeostatic afferent processing network (HAPN), a group of brain regions important to the affective and cognitive response to pain. The proposed research will examine the response of these same brain regions to more generalized stimuli (somatic and visceral), and then assess the influence of centrally-acting IBS therapies on these brain regions. The overarching hypothesis of this research is that abnormal HAPN responses to visceral stimuli have mechanistic relevance in IBS, particularly in the subset with comorbid somatization (IBS- S+). A series of relevant, multidisciplinary mentorship and career development activities also are described, including additional training in neuroanatomy and functional neuroimaging, as building blocks for a career as an independent investigator IBS neuropathophysiology. PUBLIC HEALTH RELEVANCE: This study will examine brain responses to bowel pain signals in irritable bowel syndrome (IBS). It is hypothesized that in a portion of IBS subjects, particularly those with multiple pain syndromes ("somatization"), abnormal brain interpretation of bowel signals may be responsible for the pain of IBS, and moreover may affect patient responses to proven treatments.

描述（由申请人提供）：NIDDK K23指导的以患者为导向的研究职业发展奖被要求为格雷戈里S。Sayuk，医学博士，公共卫生硕士继续严格的指导方法培训计划和调查中枢神经系统在肠易激综合征（IBS）中的病理生理作用。IBS是一种常见的腹痛疾病，影响多达五分之一的人。我们对IBS潜在机制的认识有限，导致缺乏针对性的IBS治疗。虽然在过去，评估IBS的机制基础的研究集中在肠道特异性因素，最近的证据表明，在IBS的发展异常的大脑反应外周疼痛信号的潜在作用。研究者特别感兴趣的是IBS与躯体化的重叠，这是一种以多种原因不明的疼痛合并症为特征的疾病。存在于三分之一的IBS受试者中，躯体化导致IBS临床结果较差。申请人研究的总体目标是：（1）阐明躯体化影响IBS患者大脑对外周疼痛信号反应的机制，以及（2）确定基于躯体化存在的CNS反应差异是否与IBS症状体验相关。拟议的调查是初步数据的逻辑延伸，初步数据提供了在稳态传入处理网络（HAPN）内大脑激活的独特IBS-躯体化模式的初步证据，HAPN是一组对疼痛的情感和认知反应很重要的大脑区域。拟议的研究将检查这些相同的大脑区域对更广泛的刺激（躯体和内脏）的反应，然后评估中枢作用IBS疗法对这些大脑区域的影响。本研究的总体假设是，内脏刺激的异常HAPN反应在IBS中具有机制相关性，特别是在伴有躯体化的亚组（IBS-S+）中。一系列相关的，多学科的指导和职业发展活动也被描述，包括神经解剖学和功能性神经影像学的额外培训，作为IBS神经病理生理学独立研究者职业生涯的基石。 公共卫生相关性：本研究将检查肠易激综合征（IBS）患者的大脑对肠疼痛信号的反应。假设在一部分IBS受试者中，特别是具有多种疼痛综合征（“躯体化”）的那些受试者中，肠信号的异常大脑解释可能是IBS疼痛的原因，并且此外可能影响患者对已证实的治疗的反应。