Subsynovial Connective Tissue and Carpal Tunnel Syndrome

描述(由申请人提供)：腕管综合征(CTS)是美国最常见的与工作相关的残疾原因之一。最常见的病理表现是非炎症性滑膜纤维化和增厚，但这种纤维化是CTS特有的正中神经压迫神经病的原因，还是仅仅与其相关的发现尚不清楚。本研究试图通过研究滑膜的运动行为、力学特性和生物反应来解决这一重要问题，特别是滑膜下结缔组织(SSCT)，它是连接腕管中肌腱和滑膜的滑动界面。我们假设SSCT可能发生活动性损伤，导致腕管纤维化、弹性减弱和滑动阻力增加，建立进行性损伤的恶性循环，最终损害滑膜的通透性，增加腕管压力，从而导致CTS的正中神经病变。为了检验这一假设，我们提出了三个具体目标。目的1是通过视频、透视和超声成像，描述SSCT在正常人身体、CTS患者和CTS候选动物模型(狗和兔)中的运动特征；在目标2，将研究和比较这些相同组的SSCT的力学特性和通透性。目的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病因的这一假说是正确的，则将首次建立作为CTS病因学的累积创伤的生物学基础。此外，还将为CTS的进一步实验研究确定合适的动物模型。最后，将提供一个新的视角，作为CTS新疗法和预防战略的基础。

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.