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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR049823-09
Application #
8048167
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2003-04-15
Project End
2013-09-30
Budget Start
2011-04-01
Budget End
2013-09-30
Support Year
9
Fiscal Year
2011
Total Cost
$401,514
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Matsuura, Yusuke; Thoreson, Andrew R; Zhao, Chunfeng et al. (2016) Development of a hyperelastic material model of subsynovial connective tissue using finite element modeling. J Biomech 49:119-122
Yang, Tai-Hua; Thoreson, Andrew R; Gingery, Anne et al. (2015) Collagen gel contraction as a measure of fibroblast function in carpal tunnel syndrome. J Biomed Mater Res A 103:574-80
Yang, Tai-Hua; Thoreson, Andrew R; Gingery, Anne et al. (2015) Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis. J Orthop Res 33:668-74
Filius, Anika; Scheltens, Marjan; Bosch, Hans G et al. (2015) Multidimensional ultrasound imaging of the wrist: Changes of shape and displacement of the median nerve and tendons in carpal tunnel syndrome. J Orthop Res 33:1332-40
Filius, Anika; Thoreson, Andrew R; Yang, Tai-Hua et al. (2014) The effect of low- and high-velocity tendon excursion on the mechanical properties of human cadaver subsynovial connective tissue. J Orthop Res 32:123-8
Chikenji, Takako; Gingery, Anne; Zhao, Chunfeng et al. (2014) Transforming growth factor-? (TGF-?) expression is increased in the subsynovial connective tissue in a rabbit model of carpal tunnel syndrome. PLoS One 9:e108312
Gingery, Anne; Yang, Tai-Hua; Passe, Sandra M et al. (2014) TGF-? signaling regulates fibrotic expression and activity in carpal tunnel syndrome. J Orthop Res 32:1444-50
Wang, Yuexiang; Filius, Anika; Zhao, Chunfeng et al. (2014) Altered median nerve deformation and transverse displacement during wrist movement in patients with carpal tunnel syndrome. Acad Radiol 21:472-80
Chikenji, Takako; Gingery, Anne; Zhao, Chunfeng et al. (2014) Transforming growth factor-? (TGF-?) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome. J Orthop Res 32:116-22
Ozasa, Yasuhiro; Gingery, Anne; Thoreson, Andrew R et al. (2014) A comparative study of the effects of growth and differentiation factor 5 on muscle-derived stem cells and bone marrow stromal cells in an in vitro tendon healing model. J Hand Surg Am 39:1706-13

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