Complex Persistent Pain Conditions: Unique & Shared Pathways of Vulnerability
复杂的持续性疼痛状况:独特
基本信息
- 批准号:8273089
- 负责人:
- 金额:$ 20.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-30 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): The current proposal is a competitive revision to the Program Project (2P01NS045685-06A1-PI Dr Maixner) in which we propose to explore the role of mitochondrial inheritance as a shared pathway for co-morbid Complex Persistent Pain (CPP) conditions. Our group has recent data suggesting that certain mitochondrial DNA (mtDNA) polymorphisms are associated with several CPP, including migraine and IBS, suggesting that impaired energy metabolism may be a shared pathway. In this revision we will explore the relationship between polymorphic changes in the entire mtDNA to identify candidate polymorphisms associated with CPP. This is a novel pathway to be explored in CPP and fits seamlessly into the goals of the Program Project. Exploring mtDNA, in addition to nuclear DNA, psychological and physiological factors as already proposed in this program project grant, would enhance our understanding of the shared risk factors for complex persistent pain disorders. To this end, existing blood samples obtained in the project grant will be used for genetic analyses, supplemented with banked samples. In a subgroup (N=400) of patients and controls, we will cyclosequence the entire mtDNA. Any polymorphism demonstrating a potential trend association with CPP, will be studied by PCR-RFLP in the whole sample (N=1850). In addition, detailed pedigrees will be obtained to determine the presence and degree of a maternal inheritance pattern of functional symptoms/disorders and association with identified polymorphisms. Data collected on mtDNA will be integrated with nuclear genetic data for analysis and modeling within the original aims of the PPG. Identification of disease-associated mtDNA sequence variants could provide mechanistic insight and clinical advances, and establish a new pathogenic model for understanding mtDNA-mediated polygenic susceptibility in CPP.
描述(由申请人提供):当前提案是对计划项目(2 P01 NS 045685 - 06 A1-PI Dr Maixner)的竞争性修订,我们建议在该项目中探索线粒体遗传作为共病复杂持续性疼痛(CPP)病症的共享途径的作用。我们的研究小组最近的数据表明,某些线粒体DNA(mtDNA)多态性与几种CPP相关,包括偏头痛和IBS,这表明能量代谢受损可能是一个共同的途径。在这次修订中,我们将探讨整个mtDNA的多态性变化之间的关系,以确定与CPP相关的候选多态性。这是一个新的途径,将在CPP探索,并无缝地融入计划项目的目标。探索mtDNA,除了核DNA,心理和生理因素已经提出了在这个程序项目资助,将提高我们的理解复杂的持续性疼痛障碍的共同风险因素。为此,将利用项目赠款中获得的现有血液样本进行遗传分析,并辅以库存样本。在患者和对照组的一个亚组(N=400)中,我们将对整个mtDNA进行环测序。将在整个样本(N=1850)中通过PCR-RFLP研究证明与CPP潜在趋势相关的任何多态性。此外,将获得详细的谱系,以确定功能性症状/疾病的母体遗传模式的存在和程度,以及与已鉴定多态性的相关性。收集的mtDNA数据将与核遗传数据相结合,用于PPG最初目标范围内的分析和建模。鉴定疾病相关的mtDNA序列变异可以提供机制的见解和临床进展,并建立一个新的致病模型,了解mtDNA介导的多基因易感性CPP。
项目成果
期刊论文数量(0)
专著数量(0)
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WILLIAM MAIXNER其他文献
WILLIAM MAIXNER的其他文献
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{{ truncateString('WILLIAM MAIXNER', 18)}}的其他基金
Role of Preoperative Baroreflex Sensitivity on Postoperative and Persistent Pain after Thoracic Surgery
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9809527 - 财政年份:2019
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$ 20.37万 - 项目类别:
SCREENING FOR UNC NEUROSENSORY DISORDERS PROJECTS
北卡罗来纳大学神经感觉障碍项目的筛选
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7716815 - 财政年份:2008
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- 批准号:
7625605 - 财政年份:2006
- 资助金额:
$ 20.37万 - 项目类别:
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