Human Spinal Cord Glial Cytokines and Chronic Pain

人脊髓神经胶质细胞因子和慢性疼痛

基本信息

批准号：
7479323
负责人：
Cheri Lee Lubahn
金额：
$ 33.95万
依托单位：
BANNER SUN HEALTH RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-25 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7479323
关键词：
Abbott brand of buflomedil hydrochloride Address Affect Age Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Area Astrocytes Autopsy Birds Blood Brain Cerebrospinal Fluid Cessation of life Characteristics Chronic Chronic Fatigue Syndrome Cities Clinic Clinical Clinical Data Clinical Management Clinical Research Clinical assessments Communities Complement Activation Condition Consent Data Databases Diagnosis Diagnostic Dorsal Drug Delivery Systems Enrollment Environment Enzyme-Linked Immunosorbent Assay Evaluation Fatigue Fibromyalgia Freezing Fresh Tissue Future Gastrointestinal Diseases Goals Health Hour Human Human Resources Industry Inflammation Inflammatory Interleukin-1 Interleukin-6 Investigation Knowledge Lead Life Ligaments Link Maintenance Mediator of activation protein Medical Mental Depression Messenger RNA Microglia Modeling Motor Activity Musculoskeletal Neurodegenerative Disorders Neuroglia Neurology Neuropsychology Neurosciences Numbers Pain Pain Research Pain-Free Pathologic Patients Peripheral Nerves Pharmacologic Substance Polymerase Chain Reaction Prevalence Process Production Proteins Psyche structure Quality of life Rattus Recording of previous events Recruitment Activity Regulation Reporting Research Research Institute Research Personnel Resource Sharing Resources Retirement Rodent Role Schedule Scientist Secure Serum Skeletal Muscle Sleep Disorders Source Spinal Spinal Cord Spinal nerve structure Symptoms Syndrome System Tendon structure Testing Therapy Clinical Trials Time Tissue Banks Tissue Donations Tissue Donors Tissues To specify Transcript Tumor Necrosis Factor-alpha Tumor Necrosis Factors United States Woman animal data base chronic pain clinically relevant cytokine dorsal horn drug development human TNF protein human TYRP1 protein interest novel programs

Abbott brand of buflomedil hydrochloride Address Affect Age Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Area Astrocytes Autopsy Birds Blood Brain Cerebrospinal Fluid Cessation of life Characteristics Chronic Chronic Fatigue Syndrome Cities Clinic Clinical Clinical Data Clinical Management Clinical Research Clinical assessments Communities Complement Activation Condition Consent Data Databases Diagnosis Diagnostic Dorsal Drug Delivery Systems Enrollment Environment Enzyme-Linked Immunosorbent Assay Evaluation Fatigue Fibromyalgia Freezing Fresh Tissue Future Gastrointestinal Diseases Goals Health Hour Human Human Resources Industry Inflammation Inflammatory Interleukin-1 Interleukin-6 Investigation Knowledge Lead Life Ligaments Link Maintenance Mediator of activation protein Medical Mental Depression Messenger RNA Microglia Modeling Motor Activity Musculoskeletal Neurodegenerative Disorders Neuroglia Neurology Neuropsychology Neurosciences Numbers Pain Pain Research Pain-Free Pathologic Patients Peripheral Nerves Pharmacologic Substance Polymerase Chain Reaction Prevalence Process Production Proteins Psyche structure Quality of life Rattus Recording of previous events Recruitment Activity Regulation Reporting Research Research Institute Research Personnel Resource Sharing Resources Retirement Rodent Role Schedule Scientist Secure Serum Skeletal Muscle Sleep Disorders Source Spinal Spinal Cord Spinal nerve structure Symptoms Syndrome System Tendon structure Testing Therapy Clinical Trials Time Tissue Banks Tissue Donations Tissue Donors Tissues To specify Transcript Tumor Necrosis Factor-alpha Tumor Necrosis Factors United States Woman animal data base chronic pain clinically relevant cytokine dorsal horn drug development human TNF protein human TYRP1 protein interest novel programs

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项目摘要

DESCRIPTION (provided by applicant): Fibromyalgia (FM) is characterized by chronic pain, tenderness, and stiffness in skeletal muscle. FM afflicts 4 to 6 million people in the US, 80% of which are women. Chronic fatigue syndrome (CFS) is very similar to FM. About 75% of patients meeting the diagnostic criteria of CFS also meet the diagnostic criteria for FM. There is a linear increase in the prevalence of FM up to the eighth decade of life. Chronic pain in FM patients is not well managed in the clinic, severely affects their quality of life, and limits mobility and motor activities. We are proposing to establish a tissue bank to make brain and spinal cord tissue available to study FM. Further, we propose to use the collected spinal cord tissue to determine the extent to which chronic pain in FM patients is associated with glial activation and concomitant proinflammatory cytokine production. Glial activation is linked in animal models to pain facilitation. While studying rodent pain models has proven fruitful, there is a critical need to extend investigations from rodents to humans. Rodent studies predict that glial activation and glial proinflammatory products (e.g. tumor necrosis factor (TNF), interleukin-1 (IL-1) and IL-1B) will be key spinal mediators in human chronic pain. It is critical to test the extent that glia are involved in human pain regulation. It cannot be assumed based on animal data that glial activation and their proinflammatory cytokine products are associated with human chronic pain. Mechanisms of pain facilitation elucidated using animal models have at times proven disappointing when applied to human chronic pain. This is a critical problem because until this information becomes available, it will not be possible to develop drugs targeting glial activation or their inflammatory products for chronic pain treatment. The studies also will extend our knowledge of basic mechanisms in FM pain. The objectives of this application are 1) to increase enrollment of FM patients into the brain donation program at the Sun Health Research Institute (SHRI), collect relevant clinical data and to obtain blood, cerebrospinal fluid, spinal cords and brains from enrolled patients rapidly after death and 2) to determine the extent to which FM patients have glial activation or proinflammatory cytokine production in pain-processing areas of the brain and spinal cord using the tissue collected. These objectives will be fulfilled by completing the following Specific Aims: 1) we will actively recruit and enroll FM patients into the existing brain/spinal cord donation program at SHRI. 2) We will assess the extent to which there is immunohistochemical, mRNA or protein evidence of glial activation and proinflammatory cytokine production in spinal tissues of FM patients compared to age matched pain free controls. A research team that uniquely combines experts in pain research, FM, neurology, neuropsychology and personnel with extensive expertise with a neuroscience clinical research center and CMS tissue donation program have been assembled to complete these Aims.

描述（由申请人提供）：纤维肌痛（FM）的特征是骨骼肌肉的慢性疼痛，压痛和僵硬。 FM在美国有4至600万人受苦，其中80％是女性。慢性疲劳综合征（CFS）与FM非常相似。符合CFS诊断标准的患者中约有75％符合FM的诊断标准。到生命的第八个十年，FM的流行率有线性的增加。 FM患者的慢性疼痛在诊所无法很好地治疗，严重影响其生活质量，并限制了活动能力和运动活动。我们建议建立一个组织库，以使大脑和脊髓组织可用于研究FM。此外，我们建议使用收集的脊髓组织来确定FM患者的慢性疼痛与神经胶质激活和伴随促炎性细胞因子产生有关的程度。神经胶质激活在动物模型中与疼痛促进联系起来。在研究啮齿动物疼痛模型的同时，事实证明，至关重要的需要将研究从啮齿动物扩展到人类。啮齿动物研究预测，神经胶质激活和神经胶质促炎产物（例如肿瘤坏死因子（TNF），白介素1（IL-1）和IL-1B）将是人类慢性疼痛的关键脊柱介体。测试神经胶质参与人类疼痛调节的程度至关重要。基于动物数据不能假定神经胶质激活及其促炎细胞因子产品与人类慢性疼痛有关。使用动物模型阐明的疼痛促进机制有时在应用于人类慢性疼痛的情况下被证明令人失望。这是一个关键的问题，因为在获得此信息之前，不可能开发出靶向神经胶质激活或其炎症产物进行慢性疼痛治疗的药物。这些研究还将扩展我们对FM疼痛中基本机制的了解。该应用的目标是1）增加FM患者在Sun Health Research Institute（SHRI）的大脑捐赠计划中的入学率，收集相关的临床数据，并获得血液，脑脊液，脊髓液，脊髓和大脑在死亡后迅速和2次的患者，以确定在哪些FM患者中遇到的疼痛或脑部肿瘤生产的程度）收集。这些目标将通过完成以下特定目的来实现：1）我们将积极招募和招募FM患者进入Shri现有的大脑/脊髓捐赠计划。 2）我们将评估FM患者的脊柱脊髓组织中神经胶质激活和促炎性细胞因子的产生的免疫组织化学，mRNA或蛋白质证据的程度，与年龄相匹配的无疼痛对照组相比。与神经科学临床研究中心和CMS组织捐赠计划的广泛专业知识，具有广泛专业知识的疼痛研究，FM，神经心理学和人员的独特专家的研究团队已经组装了这些目标，以完成这些目标。