Pain Mechanisms of Knee Joint Osteoarthritis

膝关节骨关节炎的疼痛机制

基本信息

批准号：
8502248
负责人：
Hee-Jeong Im Sampen
金额：
$ 32.7万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8502248
关键词：
Acute Pain Address Affect Afferent Neurons Analgesics Animal Model Animals Area Arthralgia Arthritis Attenuated Back Pain Behavioral Biological Cartilage Chronic Clinical Clinical Protocols Degenerative Disorder Degenerative polyarthritis Development Disease Down-Regulation Drug Targeting Esthesia Etiology Event Human Inflammation Injury Intervention Investigation Joints Knee Knee Osteoarthritis Knee joint Knowledge Link Medial meniscus structure Meniscus structure of joint Modeling Molecular Mus Musculoskeletal Neuritis Nociception Nociceptors Operative Surgical Procedures Osteoarthrosis Deformans Pain Pain Measurement Pathway interactions Patients Peptides Perception Peripheral Pharmacotherapy Phase Quality of life Rattus Regulation Reporting Research Resistance Role Signal Pathway Signal Transduction Source Spinal Spinal Cord Spinal Ganglia Staging Symptoms Synovial Membrane TIMP3 gene Testing Therapeutic Time Tissues angiogenesis arthropathies attenuation base bone chronic pain dorsal horn economic cost effective therapy gain of function in vivo inflammatory neuropathic pain inhibitor/antagonist innovation joint injury knee pain loss of function mechanical allodynia novel psychological distress repaired response socioeconomics tool translational study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Patients suffering from persistent knee joint pain typically have cartilage degeneration with structural and morphological changes in synovium, meniscus and subchondral bone at the damage knee joint region. Osteoarthritis is a leading cause of musculoskeletal-associated pain, psychological distress, impaired quality of life, and staggering socio-economic costs (estimated at $100 billion per year in the US alone). Currently, there is no effective treatment for this common affliction. Relief of knee joint pain is hampered because causative mechanisms (e.g., the pain source and affected cellular pathways) have not yet been established. To investigate the etiology of back pain and assess opportunities for possible clinical intervention, we will investigate specific signaling pathways leading to knee joit osteoarthritis and its symptom, knee pain by using representative tools: 1) established OA animal model model for facilitating behavioral pain assessments that allow us to investigate pain mechanisms, 2) genetically modified mice to understand pathophysiological nociceptive pathway evoked by knee osteoarthritis, and 3) investigation of peripheral (dorsal root ganglions) and central (spinal dorsal horn) responses by knee joint OA and roles of glial activation in chronic knee joint osteoarthritic pain. Our studies may uncover the nociceptive pathway that is impaired in OA condition, and may reveal that alleviation of OA pain at the spinal level is indeed beneficial to the joints by arresting progressive cartilage destruction through neurogenic attenuation. Successful completion of these studies will establish that effective controls of the PKC axis not only protects peripheral knee joint tissues from further degeneration, but also relieves its clinically debilitating symptom, pain, that profoundly impacts on the quality of life or a vast number of patients.

描述（由申请人提供）：患有持续性膝关节疼痛的患者通常存在软骨退变，损伤膝关节区域的滑膜、半月板和软骨下骨发生结构和形态变化。骨关节炎是导致肌肉骨骼相关疼痛、心理困扰、生活质量受损和惊人社会经济成本（仅在美国每年就达 1000 亿美元）的主要原因。目前，这种常见疾病尚无有效治疗方法。由于尚未确定致病机制（例如疼痛来源和受影响的细胞途径），因此膝关节疼痛的缓解受到阻碍。为了研究背痛的病因并评估可能的临床干预机会，我们将使用代表性工具研究导致膝关节骨关节炎及其症状、膝痛的特定信号通路：1）建立 OA 动物模型，以促进行为疼痛评估，让我们能够研究疼痛机制，2）转基因小鼠了解膝骨关节炎引起的病理生理伤害性通路，3）外周（背根神经节）和中枢的研究（脊髓背角）膝关节 OA 的反应以及神经胶质细胞激活在慢性膝关节骨关节炎疼痛中的作用。我们的研究可能会揭示骨关节炎情况下受损的伤害性通路，并可能揭示通过神经源性衰减阻止渐进性软骨破坏，减轻脊柱水平的骨关节炎疼痛确实对关节有益。这些研究的成功完成将证明，有效控制 PKC 轴不仅可以保护周围膝关节组织免于进一步退化，还可以缓解其临床衰弱症状和疼痛，这对大量患者的生活质量产生深远影响。