Molecular Profiling Core

摘要： 分子图谱核心。纤维肌痛(FM)、肠易激综合征(IBS)、外阴前庭炎综合征(WS)和发作性偏头痛(EM)是常见的复杂性持续性疼痛(CPPC)。CPPC通常聚集为合并症，其特征是报告的疼痛比体检时预期的要大。由于我们不了解CPPC的发病机制，患者接受的治疗不足 并遭受严重的生理、心理和社会经济后果。最近的研究表明，CPPC在很大程度上是由基因变异介导的，基因变异可以对蛋白质的数量和/或活性产生功能影响，从而调节影响疼痛相关过程的下游信号事件。然而，关于基因型和生物活性之间的关系的具体性质以及它们与临床表型的相关性还知之甚少。因此，分子图谱核心的目标是确定对CPPC有贡献的生物介体。这一目标将通过执行三个具体目标来实现。在AIM I，FM、IBS、WS和EM病例和无疼痛对照(每组N=300)将使用我们的研究团队开发的疼痛研究小组进行基因分型，以测量350个基因中近3,000个基因的多态，这些基因的蛋白产物与影响疼痛传递、炎症反应或心理状态的生物通路有关。在AIM II中，疼痛研究小组代表的350个基因对应的蛋白质表达的变化将使用定制的蛋白质微阵列技术在患者和对照组的血浆和白细胞中进行测量。 这些研究的结果将使我们能够评估直接由功能多态导致的蛋白质表达模式的变化。此外，他们将为与AIM III相关的研究的设计提供信息，该研究旨在创建一个淋巴母细胞储存库，该储存库将提供一个体内系统，在其中基于基因和蛋白质分析对细胞信号过程进行建模。阐明其基础的病理生理机制 CPPC将促进我们计划的长期目标，即为患有这些疾病的个人提供更准确的亚诊断和个性化的治疗方案。

Abstract: Molecular Profiling Core. Fibromyalgia (FM), irritable bowel syndrome (IBS), vulvar vestibulitis syndrome (WS), and episodic migraine (EM) are prevalent complex persistent pain conditions (CPPCs). CPPCs commonly aggregate as comorbid conditions and are characterized by a report of pain greater than expected upon physical examination. Because we do not understand the efiology of CPPCs, patients receive inadequate treatment and suffer severe physiologic, psychologic, and socioeconomic consequences. Recent studies suggest that CPPCs are mediated in large part by genefic variability which can produce functional consequences on the amount and/or activity of proteins, which regulate downstream signaling events that impact pain-relevant processes. However, little is known about the specific nature of the relationship between genotype and biologic activity and their relevance to clinical phenotype. Thus, the objective of the Molecular Profiling Core is to identify biologic mediators that contribute to CPPCs. This goal will be achieved through execution of three specific aims. In Aim I, FM, IBS, WS, and EM cases and pain free controls (N = 300 per group) will be genotyped using the Pain Research Panel developed by our investigative team to measure neariy 3,000 polymorphisms in 350 genes whose protein products are linked to biologic pathways that influence pain transmission, inflammatory response, or psychological state. In Aim II, changes in the expression of proteins corresponding to the 350 genes represented on the Pain Research Panel will be measured in plasma and leukocytes from cases and controls using custom protein microarray technology. Results of these studies will allow us to evaluate changes in protein expression patterns that direcfiy result from functional polymorphisms. Moreover, they will inform the design of studies associated with Aim III, which is to create a lymphoblast repository that will provide an in vivo system within which to model cell signaling processes based on genefic and protein analyses. Elucidating the pathophysiologic mechanisms that underlie CPPCs will facilitate the long-term goal of our program which is to provide more accurate subdiagnoses as well as individualized therapeutic regimens to individuals who suffer from these conditions.