Subsynovial Connective Tissue and Carpal Tunnel Syndrome

滑膜下结缔组织和腕管综合征

• 批准号: 6732780
• 负责人: Peter C. Amadio
• 金额: $ 27.34万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732780
• 关键词: biomechanics; carpal tunnel syndrome; clinical research; collagen; connective tissue; connective tissue growth factor; decorin; digital imaging; disease /disorder etiology; dogs; human subject; immunocytochemistry; laboratory rabbit; light microscopy; membrane permeability; pathologic process; postmortem; scanning transmission electron microscopy; sensory neuropathy; statistics /biometry; synovial membrane; tendon injury; transmission electron microscopy

DESCRIPTION (provided by applicant): Carpal tunnel syndrome (CTS) is one of the most common causes of work-related disability in the US. The most common pathological finding is non-inflammatory synovial fibrosis and thickening, but whether this fibrosis is a cause of, or merely an associated finding with the compression neuropathy of the median nerve that is characteristic of CTS is unknown. This study will attempt to address this important issue by investigating the motion behavior, mechanical properties, and biological response of the synovium, and specifically the subsynovial connective tissue (SSCT), the gliding interface which links the tendons and synovium in the carpal tunnel. We hypothesize that activity-related damage may occur to the SSCT, resulting in fibrosis, diminished elasticity and increased gliding resistance in the carpal tunnel, setting up a vicious cycle of progressive injury that ultimately impairs permeability of the synovium, increases carpal tunnel pressure, and thereby causes the median neuropathy of CTS. To test this hypothesis, we propose three Specific Aims. Aim 1 is to describe the motion characteristics of the SSCT, by video, fluoroscopic, and ultrasound imaging, in normal human cadavers, patients with CTS, and in candidate animal models of CTS (dog and rabbit); in Aim 2, the mechanical properties and permeability of the SSCT in these same groups will be studied and compared. Aim 3 will characterize the histology and immunohistochemistry of the SSCT in these tissues; if this hypothesis regarding the etiology of CTS is correct, a biological basis for cumulative trauma as an etiology will be established for the first time for CTS. In addition, suitable animal models will be characterized for further experimental investigations of CTS. Finally, a new perspective would be provided, which could serve as a foundation for new therapies and prevention strategies for CTS.

描述（由申请人提供）：腕管综合征（CTS）是美国与工作有关的残疾的最常见原因之一。最常见的病理发现是非炎性滑膜纤维化和增厚，但这种纤维化是否是CTS特征性正中神经压迫性神经病变的原因或仅仅是相关发现尚不清楚。本研究将试图通过研究滑膜的运动行为、力学特性和生物学反应来解决这一重要问题，特别是滑膜下结缔组织（SSCT），它是腕管中连接肌腱和滑膜的滑动界面。我们假设，活动相关的损害可能发生在SSCT，导致纤维化，弹性下降，增加滑动阻力的腕管，建立一个恶性循环的渐进性损伤，最终损害滑膜的渗透性，增加腕管压力，从而导致正中神经病变的CTS。为了验证这一假设，我们提出了三个具体目标。目的1是通过视频、荧光透视和超声成像描述正常人尸体、CTS患者和CTS候选动物模型（犬和兔）中SSCT的运动特征;目的2将研究和比较这些相同组中SSCT的机械性能和渗透性。目标3将描述这些组织中SSCT的组织学和免疫组织化学特征;如果关于CTS病因的假设是正确的，则将首次为CTS建立累积创伤作为病因的生物学基础。此外，合适的动物模型将被表征为CTS的进一步实验研究。最后，为CTS的新治疗和预防策略提供了新的视角。