Influence of Somatization on Central Pain Responses in Irritable Bowel Syndrome

描述(由申请人提供)：申请NIDDK K23指导患者导向研究职业发展奖，以支持医学博士Gregory S.Sayuk继续进行指导方法学培训和研究中枢神经系统在肠易激综合征(IBS)中的病理生理作用的严格计划。IBS是一种常见的腹痛障碍，影响多达五分之一的人。我们对IBS潜在机制的认识有限，导致缺乏有针对性的IBS治疗。虽然过去评估IBS的机制基础的研究主要集中在肠道特异性因素上，但最近的证据表明，大脑对外周疼痛信号的异常反应在IBS的发展中可能起到了作用。研究人员特别感兴趣的是IBS与躯体化的重叠，这种情况的特征是多种原因不明的疼痛共病。在三分之一的IBS受试者中，躯体化导致较差的IBS临床结果。申请者研究的总体目标是：(1)阐明躯体化影响IBS患者对外周疼痛信号的大脑反应的机制，(2)确定基于躯体化的中枢神经系统反应的这些差异是否与IBS症状体验相关。拟议的研究是初步数据的合乎逻辑的扩展，初步证据表明，在稳态传入加工网络(HAPN)内，大脑激活的独特IBS-躯体化模式，HAPN是一组对疼痛的情感和认知反应重要的大脑区域。这项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，然后评估中枢作用的IBS疗法对这些大脑区域的影响。本研究的总体假设是，腹侧核对内脏刺激的异常反应在肠易激综合征中具有机械相关性，尤其是在伴有躯体化的亚组(肠易激综合征-S+)中。还介绍了一系列相关的、多学科的指导和职业发展活动，包括神经解剖学和功能神经成像方面的额外培训，作为作为IBS神经病理生理学独立研究员的职业生涯的基石。

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.