Carpal Tunnel Syndrome and Subsynovial Connective Tissue
Carpal tunnel syndrome (CTS), a compression neuropathy of the median nerve, 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. In our progress report, we describe the histology, ultrastructure, and material properties of the SSCT in normal humans and in those with carpal tunnel syndrome, and we compare the normal human SSCT with that found in animal species which might serve as models for CTS research. This competitive renewal will address this important issue further by investigating the evolution of the motion behavior, mechanical properties, and biological response of the SSCT, and comparing that evolution to the evolution of nerve function, in a novel animal model of CTS.
The model that we have selected is based on the concept of proliferative therapy, or prolotherapy, a treatment for enthesopathies that attempts to induce cellular proliferation and fibrosis, and, thus, healing, by injection of a proliferant solution. Three classes of proliferant solutions have been described: chemical irritants, such as phenol; osmotic shock agents, such as hypertonic dextrose; and chemotactic agents, such as morrhuate sodium, a derivative of cod liver oil. We have strong preliminary evidence that a single injection of 10% dextrose into the rabbit carpal tunnel can, indeed, induce a progressive 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.
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. There are four specific aims:
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 actual clinical evolution (though not necessarily the specific inciting cause) of CTS. This model would allow us to study interventions directed at halting or reversing the evolution of SSCT fibrosis, which appears to be an important factor in the etiology and development of CTS. The model would also allow us to study the pathogenesis of CTS in more detail.
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