Subsynovial Connective Tissue and Carpal Tunnel Syndrome

滑膜下结缔组织和腕管综合征

• 批准号: 7582433
• 负责人: Peter C. Amadio
• 金额: $ 39.95万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7582433
• 关键词: Address; Animal Model; Animals; Biological; Carpal Tunnel Syndrome; Cell Proliferation; Chemicals; Clinical; Cod Liver Oil; Connective Tissue; Demyelinations; Development; Enthesopathies; Etiology; Evolution; Fibrosis; Glucose; Healed; Histology; Human; Immunohistochemistry; Inflammatory; Injection of therapeutic agent; Intervention Studies; Irritants; Median Neuropathy; Modeling; Motion; Nerve; Neuropathy; Oryctolagus cuniculus; Osmotic Shocks; Pathogenesis; Patients; Phenols; Progress Reports; Property; Research; Sodium Morrhuate; Solutions; Testing; Time; Work; base; compare effectiveness; disability; healing; mechanical behavior; median nerve; novel; pressure; prolotherapy; response

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.

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最常见原因之一。 CTS中最常见的病理发现是非炎性纤维化和亚率结缔组织（SSCT）的增厚，但是这种纤维化是造成CTS中或仅仅是CTS中相关发现的原因。这项研究将通过研究动物模型中SSCT与腕管综合症的关系来解决这一重要问题。我们选择的模型是基于增生疗法或增殖疗法的概念，一种诱导细胞增殖和纤维化的治疗方法，从而通过注射增殖溶液来愈合。我们有初步的证据表明，将10％右旋糖的单次注射到兔腕管中可以诱导与CTS患者相似的SSCT中的非炎性增生反应，最终在中间神经的脱髓鞘发展中最终导致。在这种竞争性更新中，我们建议验证这种兔模型，特别是为了测试模型中损害SSCT的假设导致纤维化的发展，材料特性改变并增加了腕管导致中​​位神经病的压力，与CTS患者相似。为了检验这一假设，我们提出了四个具体的目的：将动物模型中材料特性和腕管压力的变化与CTS患者中看到的变化；比较我们动物模型和CTS患者中SSCT的组织学，免疫组织化学和超微结构；比较我们的动物模型和CTS患者中正中神经（仅动物的神经组织学）电诊断变化的演变；并比较我们兔模型中SSCT纤维化和中位神经病进化的较高，较低和顺序葡萄糖注射的有效性。如果实现了这些目标，并且我们的假设得到了支持，那么我们将首次拥有一个验证的动物模型，该模型模仿了CT的临床演变。该模型将使我们能够研究旨在停止或逆转SSCT纤维化演变的干预措施，从而开发CTS。该模型还将使我们能够更详细地研究CTS的发病机理。