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

基本信息

批准号：
8050615
负责人：
GREGORY S SAYUK
金额：
$ 16.83万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
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/8050615
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

项目摘要

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）：请求 NIDDK K23 指导的以患者为导向的研究职业发展奖为 Gregory S. Sayuk（医学博士、公共卫生硕士）提供支持，以继续开展严格的指导方法培训计划，并调查中心的病理生理学作用肠易激综合症（IBS）的神经系统。 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 治疗方法。尽管过去评估 IBS 机制基础的研究主要集中在肠道特异性因素上，但最近出现的证据表明，大脑对周围疼痛信号的异常反应在 IBS 的发展中具有潜在作用。研究者特别感兴趣的是IBS与躯体化的重叠，躯体化是一种以多种无法解释的疼痛合并症为特征的疾病。三分之一的 IBS 受试者存在躯体化，导致 IBS 临床结果不佳。申请人研究的总体目标是：（1）阐明IBS中躯体化影响大脑对周围疼痛信号的反应的机制，以及（2）确定基于躯体化存在的中枢神经系统反应的这些差异是否与IBS相关。 IBS 症状经历。拟议的研究是初步数据的逻辑延伸，初步数据提供了稳态传入处理网络（HAPN）中大脑激活的独特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，然后评估中枢作用的 IBS 疗法对这些大脑区域的影响。这项研究的总体假设是，HAPN 对内脏刺激的异常反应与 IBS 具有机制相关性，特别是在伴有躯体化共病的子集中 (IBS-S+)。还描述了一系列相关的多学科指导和职业发展活动，包括神经解剖学和功能性神经影像学方面的额外培训，作为独立研究者 IBS 神经病理生理学的职业基础。公共健康相关性：本研究将检查肠易激综合征 (IBS) 中大脑对肠疼痛信号的反应。据推测，在部分 IBS 受试者中，特别是患有多种疼痛综合征（“躯体化”）的受试者中，大脑对肠道信号的异常解释可能是造成 IBS 疼痛的原因，此外还可能影响患者对经过验证的治疗的反应。