The Role of TNF-alpha and MAP Kinases in the Maintenance of COMT-dependent

TNF-α 和 MAP 激酶在维持 COMT 依赖性中的作用

• 批准号: 8982961
• 负责人: Jane E. Hartung
• 金额: $ 2.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2016-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8982961
• 关键词: Adrenergic Receptor; Afferent Neurons; American; Animal Model; Astrocytes; Behavioral; Biological Assay; Biological Availability; Calcium; Catechol O-Methyltransferase; Catecholamines; Cells; Cerebrospinal Fluid; Chronic; Clinical; Confocal Microscopy; Data; Development; Drug Delivery Systems; Enzymes; Fibromyalgia; Genetic; Genetic Polymorphism; Homeostasis; Hour; Image; Inflammatory; Interleukin-6; Interleukins; Link; Literature; MAPK14 gene; MAPK8 gene; Maintenance; Measures; Mechanics; Mediating; Mediator of activation protein; Microglia; Mitogen-Activated Protein Kinases; Mus; Musculoskeletal Pain; Neurobiology; Neuroglia; Neurons; Nociception; Nociceptive Stimulus; Nociceptors; Pain; Pathway interactions; Patients; Peripheral; Phosphotransferases; Physiology; Play; Rattus; Research; Rodent; Role; Signal Transduction; Spinal Cord; Spinal Ganglia; Techniques; Temporomandibular Joint Disorders; Testing; Time; Tissues; Treatment Efficacy; Tumor Necrosis Factor-alpha; Western Blotting; Work; calcium indicator; chronic pain; clinically relevant; cytokine; extracellular; genetic variant; human TNF protein; in vivo; inhibitor/antagonist; mitogen-activated protein kinase p38; novel; pain behavior; public health relevance; response; satellite cell; temporal measurement; transmission process

 DESCRIPTION (provided by applicant): Chronic musculoskeletal pain conditions are maladaptive and negatively impact the lives over 100 million Americans. A growing body of literature suggests that these chronic pain conditions result from imbalances in catecholamine homeostasis, which give way to increased release of pro-inflammatory molecules and increased activation of cells that transmit information about pain. Therefore, this proposal will employ a clinically-relevant animal model to [[1) determine if targeting specific pro-inflammatory molecules is able to reverse chronic pain caused by dysregulation of catecholamine homeostasis and 2) determine which cells involved in pain signal transmission play a role downstream from pro-inflammatory molecule activity.

 描述（由申请人提供）： 慢性肌肉骨骼疼痛状况是适应不良的，对超过1亿美国人的生活产生负面影响。越来越多的文献表明，这些慢性疼痛病症是由儿茶酚胺稳态失衡引起的，这导致促炎分子释放增加和传递疼痛信息的细胞活化增加。因此，该提案将采用临床相关的动物模型来[[1]确定靶向特定促炎分子是否能够逆转由儿茶酚胺稳态失调引起的慢性疼痛，以及2]确定参与疼痛信号传递的哪些细胞在促炎分子活性下游发挥作用。