Subsynovial Connective Tissue and Carpal Tunnel Syndrome

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。CTS中最常见的病理学发现是非炎性纤维化和滑膜下结缔组织（SSCT）增厚，但这种纤维化是否是CTS的原因或仅仅是CTS中的相关发现尚不清楚。本研究将通过在动物模型中研究SSCT与腕管综合征的关系来解决这一重要问题。我们选择的模型是基于增殖疗法或增殖疗法的概念，增殖疗法是一种通过注射增殖剂溶液诱导细胞增殖和纤维化并因此愈合的治疗。我们有初步证据表明，单次注射10%葡萄糖到兔腕管可以诱导SSCT的非炎症增殖反应，与CTS患者非常相似，最终导致正中神经脱髓鞘的发展。在这一竞争性更新中，我们建议验证该家兔模型，特别是检验模型中SSCT损伤导致纤维化进展、材料特性改变和腕管压力增加导致正中神经病变的假设，与CTS患者中观察到的情况相似。为了验证这一假设，我们提出了四个具体的目标：比较我们的动物模型与CTS患者中观察到的材料特性和腕管压力的变化;比较我们的动物模型与CTS患者中SSCT的组织学、免疫组织化学和超微结构;比较正中神经电诊断变化的演变在我们的动物模型和CTS患者中，比较高、低和顺序葡萄糖注射对我们的兔模型中SSCT纤维化和正中神经病变演变的有效性。如果这些目标得以实现，并且我们的假设得到支持，那么我们将首次拥有一个模拟CTS临床演变的有效动物模型。该模型将使我们能够研究针对停止或逆转SSCT纤维化演变的干预措施，从而研究CTS的发展。该模型还将使我们能够更详细地研究CTS的发病机制。

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 in CTS is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT), but whether this fibrosis is a cause of or merely an associated finding in CTS is unknown. This study will address this important issue by investigating the relationship of the SSCT to carpal tunnel syndrome in an animal model. The model that we have selected is based on the concept of proliferative therapy, or prolotherapy, a treatment that induces cellular proliferation and fibrosis, and, thus, healing, by injection of a proliferant solution. We have preliminary evidence that a single injection of 10% dextrose into the rabbit carpal tunnel can induce a non-inflammatory proliferative response in the SSCT very similar to that seen in patients with CTS, culminating eventually in the development of demyelination of the median nerve. In this competitive renewal, we propose to validate this rabbit model, specifically to test the hypothesis that damage to the SSCT in the model results in a progression of fibrosis, altered material properties and increased pressure in the carpal tunnel leading to median neuropathy, similar to that seen in CTS patients. To test this hypothesis, we propose four specific aims: to compare the changes in material properties and carpal tunnel pressure in our animal model with those seen in CTS patients; to compare the histology, immunohistochemistry and ultrastructure of the SSCT in our animal model and CTS patients; to compare the evolution of electrodiagnostic changes in the median nerve (and nerve histology in animals only) in our animal model and CTS patients; and to compare the effectiveness of higher, lower, and sequential dextrose injections on the evolution of SSCT fibrosis and median neuropathy in our rabbit model. If these aims are achieved, and our hypothesis is supported, then for the first time we will have a validated animal model which mimics the clinical evolution of CTS. This model would allow us to study interventions directed at halting or reversing the evolution of SSCT fibrosis, and thereby the development of CTS. The model would also allow us to study the pathogenesis of CTS in more detail.