Complex Persistant Pain Conditions: Unique & Shared Pathways of Vulnerability

描述（由申请人提供）：复杂持续性疼痛状况（CPPCs），如头痛状况、纤维肌痛、颞下颌紊乱、肠易激综合征和外阴前庭炎是高发和共有或共病的慢性疼痛状况。CPPCs的两个基本特征是：1)CPPCs的病因是多因素的；2)CPPCs的临床表现是多种多样的。在这个项目中，我们希望确定五种CPPCs的危险因素：纤维肌痛（FM）、发作性偏头痛（EM）、外阴前庭炎（VVS）、肠易激综合征（IBS）和颞下颌关节疾病（TMD）。此外，我们希望对每个CPPC内的患者群进行特征描述，这些患者群根据他们的病情表现以及疼痛特征（如疲劳、功能障碍、睡眠不足）而有显著差异。重要的是，我们预计一些患者群在不同的CPPC中比在任何单一的CPPC中更相似，这与我们认为CPPC的表现有一些重叠的观点是一致的。整合本计划的一个统一假设是，当多种遗传因素与环境暴露（例如伤害、感染、身体和心理压力）相结合时，通过增强疼痛敏感性和/或增加心理困扰，增加了对高度流行的CPPCs的易感性。为了解决本应用程序中描述的子项目和核心的目的和目标，一群有成就的疼痛临床医生，疼痛研究人员，心理生理学家，分子和细胞遗传学家，生物统计学家和流行病学家已经聚集在一起形成了这个项目。本项目申请中提出的研究旨在确定心理和生理风险因素、集群和相关的遗传多态性，这些因素会影响已经建立cppd的参保者的疼痛放大和心理特征。此外，拟议的研究试图描述这些遗传变异对CPPCs产生因果影响的生物学途径。

DESCRIPTION (provided by applicant): Complex persistent pain conditions (CPPCs) such as headache conditions, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and vulvar vestibulitis are high prevalent and shared or comorbid chronic pain conditions. There are two features of CPPCs that are fundamental to the aims and goals of this proposal: 1) the etiology of CPPCs is multifactorial and 2) the clinical manifestations of CPPCs are diverse. In this Program Project, we expect to identify a mosaic of risk factors for each of five CPPCs: fibromyalgia (FM), episodic migraine (EM), vulvar vestibulitis (VVS), irritable bowel syndrome (IBS), and temporomandibular joint disorders (TMD). Furthermore, we expect to characterize clusters of patients within each CPPC that vary significantly according to manifestations of their condition in addition to its painful characteristics (e.g., fatigue, dysfunction, sleep loss). Importantly, we expect some clusters of patients to be more alike across CPPCs than within any single CPPC, consistent with our view that there is some overlap in the manifestations of CPPCs. A unifying hypothesis integrating this Program is that multiple genetic factors, when coupled with environmental exposures (e.g. injury, infections, physical and psychological stress), increase the susceptibility to highly prevalent CPPCs by enhancing pain sensitivity and/or increasing psychological distress. To address the aims and goals of the subprojects and cores described in this application, a group of accomplished pain clinicians, pain researchers, psychophysiologists, molecular and cellular geneticists, biostatisticians and epidemiologists have been brought together to form this Program. Studies proposed in this Program Project application seek to identify the psychological and physiological risk factors, clusters, and associated genetic polymorphisms, that influence pain amplification and psychological profiles in enrollees who have established CPPDs. Additionally, the proposed studies seek to characterize the biological pathways through which these genetic variations causally influence CPPCs.