Complex Persistant Pain Conditions: Unique & Shared Pathways of Vulnerability

描述(申请人提供)：复杂的持续性疼痛状况(CPPC)，如头痛状况、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非常普遍的和共同或共病的慢性疼痛状况。CPPC有两个特征对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的临床表现是多样的。在这个项目中，我们希望确定五种CPPC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)和颞下颌关节紊乱病(TMD)。此外，我们预计每个CPPC中的患者群的特征除了其痛苦的特征(例如，疲劳、功能障碍、失眠)外，还会根据他们的病情表现而显著不同。重要的是，我们预计CPPC中的一些患者群比任何单个CPPC中的患者更相似，这与我们的观点一致，即CPPC的表现有一些重叠。整合该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/或增加心理痛苦，增加对高度流行的CPPC的易感性。为了达到本申请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组成了这个计划。本计划项目申请中提出的研究试图确定影响已建立CPPD的参与者的疼痛放大和心理特征的心理和生理风险因素、簇和相关的基因多态。此外，拟议的研究试图描述这些遗传变异对CPPC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.