Contribution of altered muscle hemodynamics to fatigability in older persons with

描述（由申请人提供）：纤维肌痛（FM）是一种广泛的肌肉骨骼疼痛的临床状态，伴有多个压痛点，最常见于绝经后妇女。疲劳，特别是劳累后疲劳，是该综合征的另一个标志。FM可能没有单一的病因，可能有神经内分泌，神经，免疫和肌肉骨骼成分。疲劳和易疲劳性也直接导致影响老年人生活质量的功能依赖和活动限制。虽然与合并症有关，但老年人的疲劳通常与确定的医学原因无关。与FM相关的疲劳、与疾病相关的疲劳以及疲劳症状随年龄的加重之间的关系尚未探讨。这项初步研究的目的是确定老年FM患者的肌肉生理缺陷，以及老年健康但易疲劳的个体，这可能有助于这种症状。老年正常健康妇女和妇女谁是健康的，但证明在测试过程中最疲劳，以及老年妇女诊断为FM，将进行研究。目的1将检验血流量减少和肌肉氧合减少直接导致疼痛和运动后疲劳的假设。使用新的，非侵入性的近红外漫射光谱，肌肉血流量和氧饱和度将量化之前，期间和之后的急性回合的运动。为了确定组织氧合降低的潜在机制，将在目标2中分析肌肉微血管。将通过免疫荧光检测内皮细胞抗原和检测内皮碱性磷酸酶，在肌肉活检中评估血管密度和内皮功能，并采用流动介导的扩张（FMD）试验和光学探针进行非侵入性评估。目的3将检验这一假设，即肌肉氧合减少的长期后果可能是线粒体功能受损。将进行肌肉活检的线粒体氧化磷酸化测定，包括呼吸速率和复合物I-IV活性。线粒体代谢物的异常积累可能会改变肌肉血管舒张特性，进一步降低氧的可用性，导致FM的疼痛和疲劳，以及老年人的疲劳。 公共卫生相关性：纤维肌痛在绝经后妇女中越来越常见。由于FM通常与疼痛、疲劳、睡眠障碍、抑郁、心理和情绪障碍以及认知缺陷有关，因此FM患者可能会遭受暂时性至永久性的衰弱。该项目将探讨肌肉生理学改变作为纤维肌痛患者以及经历疲劳的老年健康女性所经历的疼痛和疲劳的贡献者的作用。

DESCRIPTION (provided by applicant): Fibromyalgia (FM) is a clinical state of widespread musculoskeletal pain with multiple tender points that is most common in postmenopausal women. Fatigue, particularly post-exertional, is an additional hallmark of the syndrome. FM likely has no single etiology and may have neuroendocrine, neurologic, immune and musculoskeletal components. Fatigue and fatigability also contribute directly to functional dependence and activity limitations that impact quality of life among the aged. Although associated with co-morbidities, fatigue in the elderly is often not associated with an identified medical cause. The relationship among fatigue associated with FM, fatigue associated with disease, and exacerbation of fatigue symptoms with age are unexplored. The goal of this pilot study is to identify defects in muscle physiology of older FM patients, as well as older healthy but fatigable individuals, which may contribute to this symptom. Older normal healthy women and women who are healthy but prove most fatiguable during testing, as well as older women diagnosed with FM, will be studied. Aim 1 will test the hypothesis that decreased blood flow and reduced muscle oxygenation contribute directly to pain and post exercise fatigue. Using novel, noninvasive near-infrared diffuse optical spectroscopies, muscle blood flow and oxygen saturation will be quantified before, during and after an acute bout of exercise. To identify mechanisms underlying reduced tissue oxygenation, muscle microvasculature will be analyzed in Aim 2. Vascular density and endothelial function will be assessed in muscle biopsies by immunofluorescent detection of endothelial cell antigens and detection of endothelial alkaline phosphatase, and non-invasively with the flow-mediated dilatation (FMD) test and optical probe. Aim 3 will test the hypothesis that the long term consequence of reduced muscle oxygenation may be compromised mitochondrial function. Assays of mitochondrial oxidative phosphorylation from muscle biopsies will be performed, including respiration rates and complex I-IV activities. Aberrant accumulation of mitochondrial metabolites may alter muscle vasodilatory properties, further reducing oxygen availability contributing to the pain and fatigue of FM, as well as fatigue in the elderly. PUBLIC HEALTH RELEVANCE: Fibromyalgia is increasingly common in postmenopausal women. As FM is commonly associated with pain, fatigue, sleep disturbances, depression, psychological and mood disorders, and cognitive deficiencies, individuals with FM may suffer from temporary to permanent debilitation. This project will explore the role of altered muscle physiology as a contributor to the pain and fatigue experienced by fibromyalgic patients, as well as older healthy women experiencing fatigue.