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）：拟议的新研究将患有纤维肌痛型肌肉骨骼痛觉过敏（“尿皮质素和肌肉骨骼痛觉过敏”；12/01/08-11/30/13；Larson, P.I.）的小鼠研究扩展到人类研究。博士之间的新合作。 Larson 和 Pardo 汇集了一位基础科学家 (Larson) 和一位临床神经科学家 (Pardo)，前者对疼痛传递机制长期感兴趣，重点关注纤维肌痛患者的疼痛传递机制，后者拥有 PET 成像方面的专业知识。最初的提议是确定特定应激激素对小鼠肌肉骨骼疼痛模型的影响。新研究基于冷应激增强纤维肌痛症状的趋势，重点关注纤维肌痛患者此类疼痛的独特分布（躯干附近和近端，而不是远端和四肢）。棕色脂肪组织位于躯干和四肢近端附近，即锁骨上区域和躯干交感神经节顶部。压力通过交感神经以及周围皮肤和肌肉的络脉激活棕色脂肪组织。我们假设这种增强的交感神经张力会导致棕色脂肪组织周围的皮肤和肌肉交感神经维持的疼痛。 BIRT 研究的目标是通过确定纤维肌痛的疼痛（通过触诊、伤害性屈肌反射测量和既定的评分量表测量）是否与棕色纤维的体积 (MRI) 或葡萄糖代谢活动（组织摄取氟脱氧葡萄糖 PET）相关来检验这一假设。纤维肌痛患者的脂肪组织与对照组相比。在这些个体中，我们将评估抑制棕色脂肪活性的饮食控制是否会暂时缓解疼痛，或者是否会因暴露于寒冷而增加棕色脂肪组织活性而加剧疼痛。与母基金一样，按照原始 RO1 提案的审查者的建议，将采集样本来监测纤维肌痛患者与健康对照者的应激激素（CRF 和尿皮质素 I、II 和 III）浓度。这些研究将首次检验棕色脂肪组织中交感神经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影响。它们可以为开发新的评估和治疗策略提供新的进展。 公共健康相关性：根据 NIAMS 统计数据，每 73 人中就有 1 人 (1.35%) 或大约 370 万美国人患有纤维肌痛综合征。压力会加剧纤维肌痛的症状，但其发生机制尚不清楚。我们假设压力会增强棕色脂肪组织的交感神经张力，以及神经支配与纤维肌痛分布重叠区域的周围皮肤和肌肉的络脉的张力。如果纤维肌痛患者的棕色脂肪组织的数量或活性（使用 FDG PET 和 MRI 测定）与对照组不同，这将首次确定棕色脂肪组织的调节是导致纤维肌痛症状的潜在因素。确定导致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。