Urocortin & Musculoskeletal Hyperalgesia

尿皮质素

• 批准号: 7989277
• 负责人: ALICE A LARSON
• 金额: $ 15.1万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989277
• 关键词: Adipose tissue; American; Area; Biological Assay; Blood specimen; Brain; Brown Fat; Carbohydrates; Clinical; Collaborations; Data; Diet; Endocrine; Exposure to; Eye; Fatty acid glycerol esters; Fibromyalgia; Flexor; Glucose; Goals; Hormones; Human; Hyperalgesia; Image; Image Analysis; Individual; Intervention; Limb structure; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Metabolic; Metabolism; Modeling; Monitor; Mus; Muscle; Musculoskeletal; Musculoskeletal Pain; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nerve; Nociception; Pain; Palpation; Pathway interactions; Patients; Physiological; Positron-Emission Tomography; Proteins; Recruitment Activity; Regulation; Research; Rest; Sampling; Scientist; Skin; Stress; Study Subject; Supraclavicular; Sympathetic Ganglia; Symptoms; Testing; Therapeutic; Thermogenesis; Time; TimeLine; Tissues; base; fluorodeoxyglucose positron emission tomography; interest; novel; parent grant; psychologic; public health relevance; relating to nervous system; response; statistics; transmission process; uptake; urocortin

DESCRIPTION (provided by applicant): The proposed new studies extend those in mice with fibromyalgia-type musculoskeletal hyperalgesia ("Urocortin & Musculoskeletal Hyperalgesia"; 12/01/08-11/30/13; Larson, P.I.) to studies in humans. The new collaboration between Drs. Larson and Pardo brings together a basic scientist (Larson), who has a long- standing interest in the mechanism of pain transmission with a focus on that seen in patients with fibromyalgia, and a clinical neuroscientist (Pardo), who has expertise in PET imaging. The original proposal was to determine the effect of specific stress hormones on musculoskeletal pain models in mice. The new studies focus on the unique distribution of such pain in patients with fibromyalgia (near the trunk and proximally rather than distally and on the extremities) based on the tendency for cold stress to enhance the symptoms of fibromyalgia. Brown adipose tissue is located near the trunk and proximal extremities-- i.e., in supraclavicular areas and atop sympathetic ganglia in the trunk. Stress activates brown adipose tissue via sympathetic nerves with collaterals to surrounding skin and muscle. We hypothesize that this enhanced sympathetic tone causes sympathetically maintained pain in the skin and muscle surrounding brown adipose tissue. The BIRT research goal is to test this hypothesis by determining whether the pain of fibromyalgia, measured by palpation, nociceptive flexor reflexometry, and established rating scales, correlates with the volume (MRI) or glucose metabolic activity (tissue uptake of fluordeoxyglucose PET) of brown adipose tissue in fibromyalgia patients compared to controls. In these individuals, we will assess whether pain is temporarily relieved by dietary manipulations inhibiting brown adipose activity, or whether the pain is worsened by exposure to cold increasing brown adipose tissue activity. As in the parent grant, samples will be taken to monitor the concentrations of stress hormones (CRF and urocortins I, II and III) in fibromyalgia patients compared to healthy controls, as suggested by the reviewers of the original RO1 proposal. These studies will be the first to test the hypothesis of sympathetically mediated metabolism in brown adipose tissue and the collateral effects upon the pain in related muscles and skin in fibromyalgia syndrome. They can provide a novel inroad toward developing novel assessment and therapeutic strategies. PUBLIC HEALTH RELEVANCE: According to NIAMS statistics, 1 in 73 (1.35%) or approximately 3.7 million Americans suffer from fibromyalgia syndrome. Stress enhances the symptoms of fibromyalgia, but the mechanism by which this occurs is unknown. We hypothesize that stress enhances sympathetic tone to brown adipose tissue as well as to collaterals that innervate the surrounding skin and muscle in areas that overlap with the distribution of fibromyalgia pain. If the amount or activity of brown adipose tissue (determined using FDG PET and MRI) differs in patients with fibromyalgia from that in controls, this will, for the first time, identify the regulation of brown adipose tissue as a potential contributor to fibromyalgia symptoms. Identification of pathways that cause pain in these patients will allow us to test potential therapies and clinical interventions that relieve the symptoms of fibromyalgia.

描述（由申请人提供）：拟议的新研究将纤维肌痛型肌肉骨骼肌肉骨骼痛觉过敏（“尿素素和肌肉骨骼骨骼痛觉过敏”延伸； 12/01/08-11/30/30/13; Larson，P.I.）到人类的研究。 Drs之间的新合作。拉尔森（Larson）和帕多（Pardo）汇集了一位基本科学家（拉尔森（Larson）），他们对疼痛传播机制具有长期的兴趣，重点是纤维肌痛患者，以及临床神经科学家（Pardo），他在宠物成像方面具有专业知识。最初的建议是确定特定应激激素对小鼠肌肉骨骼疼痛模型的影响。新研究的重点是纤维肌痛患者的独特分布（靠近树干，近端而不是远端和四肢），这是基于冷应激的趋势来增强纤维肌痛的症状。棕色的脂肪组织位于树干附近，近端近端 - 即，在锁骨上区域和躯干上的交感神经节上。压力通过侧边的交感神经来激活棕色的脂肪组织，以围绕皮肤和肌肉。我们假设这种增强的交感神经声音会导致棕色脂肪组织周围的皮肤和肌肉疼痛。 BIRT研究目标是通过确定通过触诊，伤心屈肌反射法测量的纤维肌痛的疼痛和确定的评级量表是否与体积（MRI）或葡萄糖代谢活性相关（纤维糖摄入富含脂质粘液粉的脂肪症患者）与纤维组织中的纤维蛋白患者相关。在这些人中，我们将评估疼痛是否因抑制棕色脂肪活性的饮食操纵而暂时缓解，还是暴露于寒冷增加棕色脂肪组织活性来恶化疼痛。与父母的赠款一样，与健康对照组相比，纤维肌痛患者的应力激素（CRF和泌尿皮质素I，II和III）的浓度将进行，如原始RO1提案的审阅者所建议。这些研究将是第一个检验棕色脂肪组织中交感介导的代谢的假设以及对纤维肌痛综合征相关肌肉和皮肤疼痛的附带作用。他们可以为制定新颖的评估和治疗策略提供新颖的进攻。 公共卫生相关性：根据NIAMS统计数据，有73分之一（1.35％）或大约370万美国人患有纤维肌痛综合征。应力增强了纤维肌痛的症状，但是发生这种情况的机制尚不清楚。我们假设应力增强了对棕色脂肪组织的交感神经，以及在与纤维肌痛疼痛分布重叠的区域中支配周围皮肤和肌肉的侧支。如果纤维肌痛患者与对照组的患者的棕色脂肪组织的数量或活性（使用FDG PET和MRI确定）不同，这将首次确定对棕色脂肪组织的调节，作为纤维肌痛症状的潜在贡献。鉴定引起这些患者疼痛的途径将使我们能够测试缓解纤维肌痛症状的潜在疗法和临床干预措施。