Contribution of altered muscle hemodynamics to fatigability in older persons with

描述(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，具有多个压痛点，在绝经后妇女中最常见。疲劳，特别是劳累后，是该综合征的另一个特征。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。疲劳和疲劳性也直接导致功能依赖和活动受限，从而影响老年人的生活质量。虽然与并发症有关，但老年人的疲劳通常与已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剧之间的关系尚未被探索。这项先导性研究的目的是确定老年FM患者的肌肉生理学缺陷，以及可能导致这种症状的老年健康但易疲劳的人。将研究老年正常健康女性和在测试中被证明最疲惫的健康女性，以及被诊断为FM的老年女性。目标1将检验这样一个假设，即血流减少和肌肉氧合减少直接导致疼痛和运动后疲劳。使用新的无创近红外漫反射光谱仪，肌肉血流量和血氧饱和度将在急性运动之前、期间和之后进行量化。为了确定导致组织氧合减少的机制，将在AIM 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内皮碱性磷酸酶来评估肌肉活检中的血管密度和内皮功能，并使用流动介导扩张(FMD)试验和光学探针进行非侵入性评估。目的3将验证肌肉氧合减少的长期后果可能是线粒体功能受损的假设。将进行肌肉活检的线粒体氧化磷酸化分析，包括呼吸速率和复合I-IV活性。线粒体代谢产物的异常积累可能会改变肌肉的血管扩张特性，进一步降低氧的可获得性，从而导致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，FM患者可能会遭受暂时或永久性的虚弱。这个项目将探索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因素所起的作用。

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.