Subsynovial connective tissue is sensitive to surgical interventions in a rabbit model of carpal tunnel syndrome

Abstract

The most common histological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) in the tunnel. While the cause of SSCT fibrosis and the relationship of SSCT fibrosis and CTS are unknown, one hypothesis is that SSCT injury causes fibrosis, and that the fibrosis then leads to CTS. We investigated the sensitivity of the SSCT to injuries. Two types of surgical intervention were performed in a rabbit model: a skin incision with tendon laceration and SSCT stretching sufficient to damage the SSCT, and skin incision alone,. Twelve weeks after surgery, the rabbit carpal tunnel tissues were studied with immunochemistry for TGF-β receptors 1, 2, and 3, collagen III, and collagen VI. All TGF-β receptors were expressed. The percentages of the TGF-β receptors’ expressions were less in the control SSCT fibroblasts than in the fibroblasts from rabbits with surgical interventions. The surgical interventions did not result in any alteration of collagen III expression. However, both surgical interventions resulted in a significant decrease in collagen VI expression compared to the control group. The two surgical interventions achieved similar expression of TGF-β receptors and collagens. Our results provide evidence that the SSCT is sensitive to surgical interventions, even when these are modest. Since SSCT fibrosis is a hallmark of carpal tunnel syndrome, these data also suggest that such fibrosis could result from relatively minor trauma.

Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients

“…The mechanism underlying fibrosis involves the expression of collagen types I and III as a result of the up‐regulation of TGF‐β and CTGF expression by fibroblasts in the SSCT (Chikenji et al, ). Repeated minor trauma to the SSCT is believed to result in the up‐regulation of TGF‐β expression in fibroblasts in patients with idiopathic CTS (Sun et al, ). However, as it also occurs in individuals who do not overuse their hands, it may have other underlying causes.…”

Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis

“…Earlier studies that focused on pathological changes in the median nerve used balloons or other devices to elevate pressure in the carpal tunnel, causing acute and direct pressure effects. 9,25,26 More recent studies have proposed, however, that the noninflammatory fibrotic change and thickening of the SSCT is the initiating cause of the pressure elevation, and hence of the neuropathy in idiopathic CTS. 5,6,12 In a rabbit model, two injections of 10% dextrose 1 week apart induced fibrosis in the SSCT with 6 weeks, which persisted for up to 24 weeks 12-14 as well as producing, at 12 weeks, changes in nerve physiology consistent with findings in CTS patients.…”

TGF‐β signaling regulates fibrotic expression and activity in carpal tunnel syndrome

“…Non‐inflammatory synovial fibrosis is commonly observed in idiopathic CTS . Since fibrosis appears to play an important role in the pathology of this disease, we sought to characterize the fibrosis in CTS and to identify potential therapeutic targets.…”

“…Previous work has shown that even small increases in TGF‐β expression can have profound effects in the local environment and changes in receptors or second messengers such as SMAD3 can amplify the TGF‐β associated responsiveness . Given that TGF‐β is a common mediator of fibrosis in tissue and organ systems and that significant increases are found in both TGF‐β 1 and TGF‐β receptors in SSCT of CTS patients, we chose to focus on this pathway as a potential regulator and therapeutic target …”