Post exertion malaise in GWI_Brain autonomic and behavioral interactions
GWI_Brain 自主神经和行为相互作用中的劳累后不适
基本信息
- 批准号:10683715
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-01-01 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAfghanistanBehavioralBrainCardiacCardiovascular systemCaringCentral Nervous SystemCerebrovascular CirculationCharacteristicsChronicChronic Fatigue SyndromeCognitionCompensationCountryDataEvidence Based MedicineExerciseExertionFatigueFibromyalgiaFunctional Magnetic Resonance ImagingFunctional disorderGene ExpressionGlucocorticoid ReceptorGoalsGulf War veteranHealthHeart RateHomeostasisHourImmuneImmune systemImpaired cognitionImpairmentInflammation MediatorsInflammatoryInstitute of Medicine (U.S.)InterventionIraqLaboratoriesLassoLeukocytesMaintenanceMalaiseMeasuresMedicalMetabolicMethodsMissionModelingMusculoskeletal PainPainPain MeasurementPaintPathway interactionsPatientsPersian GulfPersian Gulf SyndromePhysiologicalPhysiologyPositioning AttributePosturePublishingRegulationReportingResearchResearch PersonnelRestStimulusStudy modelsSymptomsSystemTestingTimeTitrationsUnited States Department of Veterans AffairsVeteransVisceraWarWorkautonomic nervecerebrovascularclinical carecognitive functioncognitive taskcytokinedesigndisabilityefficacious treatmentexperiencehealth care service utilizationimmunoregulationimprovedindividualized medicineinstrumentneuralpain sensitivitypersonalized medicinepublic health relevanceresponsestressortargeted treatmenttherapy design
项目摘要
DESCRIPTION (provided by applicant):
The overall goal of this research is to determine the mechanisms of symptom maintenance and
exacerbation in Gulf War Veterans (GVs) suffering with Gulf War illness (GWI). To date, the pathophysiology of GWI is poorly understood, and there are currently no confirmed efficacious treatments for these Veterans. Research involving GVs and civilians with similar chronic multi-symptom illnesses (CMI) such as chronic fatigue syndrome and fibromyalgia show that multiple physiological systems are dysfunctional - principally the central, autonomic, and immune systems. Moreover, dysfunction within these systems is magnified and symptoms are exacerbated following an exercise challenge (i.e., post-exertion malaise [PEM]), providing a controllable model for the study of GWI.
Our central hypothesis is that dysfunction across multiple physiological systems interacts to
produce and maintain the symptoms of GWI, and this dysfunction is best studied via a PEM model. Our
pilot data demonstrate that compared with healthy controls, patients with CMI (including GVs) demonstrate: (1) enhanced ratings and brain responses to painful stimuli and poor cerebral vascular auto-regulation, (2) augmented ratings and neural responses to fatiguing cognitive tasks, and (3) enhanced symptoms, increased pain sensitivity, and up-regulated gene expression to exercise challenge. These systems have been primarily studied in isolation and need to be studied under the same circumstances and within the same Veterans to determine the pathophysiological significance of their interactions. The primary goals of this project will b accomplished by comparing GVs with GWI to healthy GVs. The specific aims of the project are to determine: (1) baseline function across multiple physiological systems (CNS, autonomic, immune) in GVs with and without GWI; (2) the impact of an exercise challenge on CNS regulation of pain/fatigue, cardiovascular autonomic function, and immune system activity and symptoms in GVs with and without GWI; and (3) whether interactions among multiple systems significantly explain symptoms of GWI. CNS regulation of pain/fatigue will be measured using functional magnetic resonance imaging. Autonomic regulation will be measured via cerebral blood flow and parasympathetic responses to postural challenge. Immune activity will be measured via gene expression of inflammatory mediators (i.e., pro-inflammatory cytokine, metabolic and glucocorticoid receptors). The exercise challenge will consist of a single bout of cycling on a standard cycle ergometer at 70% of predicted peak heart rate for 30 minutes. CNS regulation of paint/fatigue, autonomic regulation, and immune activity will be measured 24 hours post-exercise when Veterans are experiencing PEM. Symptoms will be measured with validated instruments to assess pain, fatigue, and cognitive impairment. Symptoms will be followed for one week after exercise challenge to characterize the presence, magnitude, and time-course of PEM in GWI. We expect that GVs with GWI will demonstrate dysfunction across multiple physiological systems, that these systems will become more impaired as a result of an exercise challenge, and that interactions among these
systems will significantly explain symptoms at baseline and during symptom exacerbation (i.e., PEM).
The goals of this project will significantly enhance our understanding of GWI and will begin to determine
the physiological systems that are most impaired. Study findings will provide the first critical steps
towards designing treatments for GWI that are mechanistically based on physiology rather than
standard approaches designed to target symptoms. These goals are consistent with a recent Institute of Medicine evidence-based review (IOM, 2014) of treatment options for Veterans of Gulf, Iraq,and Afghanistan citing the need for individualized treatments that are specific to the Veteran. This treatment approach cannot be realized without first determining the pathophysiology of GWI - the primary goal of the proposed research.
描述(由申请人提供):
这项研究的总体目标是确定症状维持和治疗的机制。
患有海湾战争疾病 (GWI) 的海湾战争退伍军人 (GV) 的病情加重 迄今为止,人们对 GWI 的病理生理学知之甚少,目前还没有针对这些退伍军人和患有类似慢性多症状的平民的有效治疗方法。慢性疲劳综合症和纤维肌痛等症状(CMI)表明多个生理系统功能失调——主要是中枢系统、自主神经系统和免疫系统,而且这些系统内的功能失调。运动挑战后(即运动后不适 [PEM]),GWI 会被放大且症状会加剧,为 GWI 的研究提供了一个可控模型。
我们的中心假设是多个生理系统的功能障碍相互作用
产生并维持 GWI 症状,这种功能障碍最好通过我们的 PEM 模型来研究。
试点数据表明,与健康对照相比,CMI(包括 GV)患者表现出:(1)对疼痛刺激的评分和大脑反应增强,脑血管自动调节能力较差,(2)对疲劳认知任务的评分和神经反应增强, (3) 运动挑战时症状增强、疼痛敏感性增加和基因表达上调。这些系统主要是单独研究的,需要在相同的情况下和在相同的退伍军人中进行研究,以确定其病理生理学意义。主要目标。该项目的具体目标是通过将具有 GWI 的 GV 与健康的 GV 进行比较来完成:(1) 有和没有 GWI 的 GV 的多个生理系统(中枢神经系统、自主神经、免疫)的基线功能;运动挑战对中枢神经系统对疼痛/疲劳、心血管自主神经功能、免疫系统活动和 GV 症状的影响,无论是否有 GWI;(3) 多个系统之间的相互作用是否能显着解释 GWI 的症状。将使用功能性磁共振成像来测量自主神经调节,并通过炎症介质(即促炎细胞因子、代谢和炎症介质)的基因表达来测量副交感神经对姿势挑战的反应。运动挑战包括在标准自行车测力计上以 70% 的预测峰值心率进行单次骑行,持续 30 分钟。当退伍军人经历 PEM 时,将在运动后 24 小时测量油漆/疲劳、自主调节和免疫活动。将使用经过验证的仪器测量症状,以评估疼痛、疲劳和认知障碍。运动后将跟踪症状一周。描述 GWI 中 PEM 的存在、强度和时间过程的挑战我们预计 GWI 的 GV 将表现出跨多个生理系统的功能障碍,这些系统将因运动挑战而变得更加受损,并且这些之间的相互作用
系统将显着解释基线时和症状恶化期间的症状(即 PEM)。
该项目的目标将显着增强我们对 GWI 的理解,并将开始确定
受损最严重的生理系统的研究结果将提供第一个关键步骤。
设计基于生理学而非机械性 GWI 的治疗方法
这些目标与最近医学研究所对海湾、伊拉克和阿富汗退伍军人治疗方案的循证审查(IOM,2014)一致,该审查指出需要针对退伍军人进行个体化治疗。如果不首先确定 GWI 的病理生理学(本研究的主要目标),这种治疗方法就无法实现。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DANE B. COOK其他文献
DANE B. COOK的其他文献
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{{ truncateString('DANE B. COOK', 18)}}的其他基金
Post exertion malaise in GWI_Brain autonomic and behavioral interactions
GWI_Brain 自主神经和行为相互作用中的劳累后不适
- 批准号:
10426235 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Post exertion malaise in GWI_Brain autonomic and behavioral interactions
GWI_Brain 自主神经和行为相互作用中的劳累后不适
- 批准号:
10291815 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Post exertion malaise in GWI_Brain autonomic and behavioral interactions
GWI_Brain 自主神经和行为相互作用中的劳累后不适
- 批准号:
9210549 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Impact of exercise training on pain and brain function in Gulf War Veterans
运动训练对海湾战争退伍军人疼痛和大脑功能的影响
- 批准号:
8277785 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Impact of exercise training on pain and brain function in Gulf War Veterans
运动训练对海湾战争退伍军人疼痛和大脑功能的影响
- 批准号:
8793726 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Impact of exercise training on pain and brain function in Gulf War Veterans
运动训练对海湾战争退伍军人疼痛和大脑功能的影响
- 批准号:
8698364 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Impact of exercise training on pain and brain function in Gulf War Veterans
运动训练对海湾战争退伍军人疼痛和大脑功能的影响
- 批准号:
8003196 - 财政年份:2011
- 资助金额:
-- - 项目类别:
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