Mechanism of Neuropathic Pain (CRPS)

神经性疼痛 (CRPS) 的机制

基本信息

批准号：
7214682
负责人：
JIN M CHUNG
金额：
$ 33.11万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-12-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7214682
关键词：
6-Cyano-7-nitroquinoxaline-2,3-dione Abbreviations Absence of pain sensation Acids Affect Analgesics Analysis of Variance Apoptosis Behavior Behavioral Biological Assay Causalgia Cell Death Cell Nucleus Cells Cerebrospinal Fluid Chronic Chronic Disease Complex Regional Pain Syndromes Count DNA DNA Fragmentation DNA Nucleotidylexotransferase Data Depth Detection Development Dimethyl Sulfoxide Electrophoresis Enzyme-Linked Immunosorbent Assay Enzymes Exposure to Figs - dietary Free Radical Scavengers Free Radicals Functional disorder Funding GABA Receptor Gel Glutamate Decarboxylase Goals Grant Heating High Pressure Liquid Chromatography Hyperalgesia Immune Impairment In Situ In Situ Nick-End Labeling Individual Injection of therapeutic agent Isomerism Isoxazoles KLK3 gene Label Lead Ligation Link Localized Measurement Measures Mechanics Mediating Medical Microdialysis Modeling N-Methyl-D-Aspartate Receptors N-Methylaspartate Names Neuro-Oncological Ventral Antigen 2 Neurons Nitric Oxide Synthase Numbers Oxides Pain Patients Peripheral Play Posterior Horn Cells Postoperative Period Preparation Propionic Acids Propionic acid Quality of life Rattus Reactive Oxygen Species Role Sepharose Series Site Slice Spinal Spinal Cord Spinal cord posterior horn Spinal nerve structure Spinothalamic Tracts TNF gene Testing Time Tumor Necrosis Factor-alpha Tumor Necrosis Factors allodynia base behavior test central sensitization gamma-Aminobutyric Acid human TNF protein improved in vivo interdisciplinary approach intraperitoneal nerve injury neuropeptide Y painful neuropathy phenyl-N-tert-butylnitrone postsynaptic presynaptic prevent synthetic enzyme tert-Butylhydroperoxide tripolyphosphate

项目摘要

DESCRIPTION (provided by applicant): Complex regional pain syndrome (CRPS) is an especially difficult medical problem because it is a chronic disease affecting a patient's quality of life, often with no effective treatment. Therefore, it is important to understand the mechanisms of CRPS, thereby allowing new treatment paradigms to be developed, which is the long-term goal of this proposal. Using the spinal nerve ligation model, an extensively used rat model of CRPS (type II with major nerve injury), various aspects of the peripheral mechanisms of CRPS has been studied in the past, with support from the present grant. In the upcoming funding period of the present grant, however, the focus will be on spinal mechanisms of CRPS. The overall hypothesis is that spinal nerve injury induces a sustained elevated level of highly toxic free radicals, reactive oxygen species (ROS), in the spinal cord, leading in turn to central sensitization of dorsal horn neurons, which is the key underlying mechanism in CRPS. Four specific aims are proposed to test the following individual hypotheses: 1) that spinal nerve ligation induces an elevated level of spinal ROS, 2) that the increased ROS are associated with central sensitization and behavioral signs of pain, 3) that an important mechanism of ROS-induced central sensitization is impairment of GABA function in the cord, and 4) that as time passes many dorsal horn neurons die due to extended exposure to ROS. The present proposal is to test these hypotheses using a multidisciplinary approach. Successful completion of these aims will not only uncover important spinal mechanisms of CRPS but may also lead to the development of new analgesic drugs based on free radical scavengers.

描述（由申请人提供）：复杂的区域疼痛综合征（CRP）是一个特别困难的医学问题，因为它是一种慢性疾病，影响了患者的生活质量，通常没有有效的治疗。因此，重要的是要了解CRP的机制，从而允许开发新的治疗范式，这是该提议的长期目标。使用脊柱神经连接模型，一种广泛使用的CRP的大鼠模型（具有重大神经损伤的II型），过去已经研究了CRP的外围机制的各个方面，并得到了目前的赠款的支持。但是，在即将到来的资助期间，重点将放在CRP的脊柱机制上。总体假设是，脊柱神经损伤诱导脊髓中持续升高的剧毒自由基，活性氧（ROS）的持续升高，导致背角神经元的中心敏化，这是CRPS中的关键基础机制。 Four specific aims are proposed to test the following individual hypotheses: 1) that spinal nerve ligation induces an elevated level of spinal ROS, 2) that the increased ROS are associated with central sensitization and behavioral signs of pain, 3) that an important mechanism of ROS-induced central sensitization is impairment of GABA function in the cord, and 4) that as time passes many dorsal horn neurons die due to extended exposure to ROS.目前的建议是使用多学科方法检验这些假设。这些目标的成功完成不仅会发现CRP的重要脊柱机制，而且还可能导致基于自由基清除剂的新镇痛药的发展。