A histological and immunohistochemical study of the subsynovial connective tissue in idiopathic carpal tunnel syndrome

Background: The most common histological finding in carpal tunnel syndrome is noninflammatory synovial fibrosis. The accumulated effect of minor injuries is believed to be an important etiologic factor in some cases of carpal tunnel syndrome. We sought evidence of such injuries in the synovial tissue of patients with carpal tunnel syndrome and in cadaver controls. Methods: We compared synovial specimens from thirty patients who had idiopathic carpal tunnel syndrome with specimens from a control group of ten fresh-frozen cadavers of individuals who had not had an antemortem diagnosis of carpal tunnel syndrome and who met the same exclusion criteria. Analysis included histological and immunohistochemical examination for the distribution of collagen types I, II, and VI and transforming growth factor-β (TGF-β) RI, RII, and RIII. Results: Histological examination showed a marked increase in fibroblast density, collagen fiber size, and vascular proliferation in the specimens from the patients compared with the control specimens (p < 0.001). Collagen types I and II were not found in the synovium of either the patients or the controls, but collagen type VI was a major component of both. Collagen type-III fibers were more abundant in the patients than in the controls (p < 0.001). Expression of TGF-β RI was found in the endothelial cells and fibroblasts in the patient and control specimens, with a marked increase in expression in the fibroblasts of the patients compared with that in the control tissue (p < 0.001). Conclusions: These findings are similar to those after injury to skin, tendon, and ligament and suggest that patients with idiopathic carpal tunnel syndrome may have sustained an injury to the subsynovial connective tissue. Clinical Relevance: The changes demonstrated in the subsynovial connective tissue not only could lead to an increase in the volume of the contents in the carpal tunnel but also may alter its material properties, such as compliance and permeability to fluid flows, and vascularity. These changes may, in turn, predispose the subsynovial connective tissue to additional injury and contribute to the elevation in carpal tunnel pressure seen in patients with carpal tunnel syndrome.