Complex Persistant Pain Conditions: Unique & Shared Pathways of Vulnerability

描述（由申请方提供）：复杂持续性疼痛病症（CPPC），如头痛病症、纤维肌痛、颞下颌关节紊乱病、肠易激综合征和外阴前庭炎，是高流行率和共享或共病的慢性疼痛病症。CPPC的两个特征对于本提案的目的和目标至关重要：1）CPPC的病因是多因素的，2）CPPC的临床表现多种多样。在这个项目中，我们希望确定五种CPPC的风险因素：纤维肌痛（FM），阵发性偏头痛（EM），外阴前庭炎（VVS），肠易激综合征（IBS）和颞下颌关节紊乱病（TMD）。此外，我们期望表征每个CPPC内的患者群，这些患者群除了其疼痛特征外，还根据其病症的表现而显著变化（例如，疲劳、功能障碍、睡眠不足）。重要的是，我们预计在CPPC之间的一些患者群比任何单一CPPC内的患者群更相似，这与我们认为CPPC的表现存在一些重叠的观点一致。整合该计划的统一假设是，多种遗传因素，当与环境暴露（例如损伤，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CPPC的易感性。为了解决本申请中描述的子项目和核心的目的和目标，一组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聚集在一起，形成了这个计划。 本计划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，这些因素影响已建立CPPD的注册者的疼痛放大和心理特征。此外，拟议的研究旨在表征这些遗传变异因果影响CPPC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.