Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome?
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ABSTRACT:
SUBMITTER: Oh S
PROVIDER: S-EPMC2528978 | biostudies-other | 2008 Mar
REPOSITORIES: biostudies-other
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Project description:Carpal tunnel syndrome (CTS) is a very common pathology. Its most common diagnosis is idiopathic. Although it is accepted that chronic increase in pressure within the carpal tunnel is responsible for median nerve neuropathy, the exact pathophysiology leading to this pressure increase remains unknown. All the histological studies of the carpal tunnel in the CTS find a noninflammatory thickening of the subsynovial connective tissue (SSCT), which seems to be a characteristic of this pathology. Numerous animal models have been developed to recreate CTS in vivo to develop and improve preventive strategies and effective conservative treatments by a better understanding of its pathophysiology. The creation of a shear injury of the SSCT in a rabbit model induced similar modifications to what is observed in CTS, suggesting that this could be a pathway leading to idiopathic CTS.
| S-EPMC4208960 | biostudies-other
Project description:Carpal Tunnel Syndrome (CTS) is the most common surgically treated problem in the hand. Aside from the neuropathy itself, the most common findings are fibrosis of the subsynovial connective tissue (SSCT) and increased intra carpal tunnel pressure. Normally, the SSCT is a multilayer tissue interspersed among the carpal tendons and nerve. As the tendons move, successive SSCT layers are recruited, forming a gliding unit and providing a limit to differential movement. Exceeding this limit, damages the SSCT as has been shown in both cadavers and animal models. This damage leads to a non-inflammatory response with progressive fibrosis and nerve ischemia leaving the SSCT more susceptible to injury. Although the direct consequences for patients are not fully understood, ultrasound research shows that this fibrosis restricts median nerve displacement during tendon loading. This article aims to provide insights into the mechanical properties of SSCT described so far and place it in the context of CTS pathophysiology. A theoretical damage model concerning the SSCT is proposed showing a chain of events and vicious cycles that could lead to the nerve compression as it is found in CTS. Although not complete, this model could explain the pathophysiological pathway of idiopathic CTS.
| S-EPMC5985810 | biostudies-literature
Project description:Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in carpal tunnel syndrome (CTS). Identification of molecular targets and anti-fibrotic therapies could provide new treatment strategies for CTS. The contribution of SSCT cells to fibrosis and the signaling pathways that initiate and aggravate fibrosis in CTS remain unknown. Here we report that platelet-derived growth factor receptor alpha (PDGFRα) positive ( + ) cells accumulate in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in increased proliferation of PDGFRα+ cells via PI3K/Akt signaling pathway. Although PI3K inhibition decreased proliferation, there was no change in fibrosis-related gene expression. Indeed, protein levels of fibrosis signaling mediator TGF-β remained the same and the second messenger, Smad2/3, accumulated in the nucleus. In contrast AMP-activated protein kinase (AMPK) activation, which can be induced with metformin and AICAR inhibited proliferation, TGF-β expression, and altered cell morphology in SSCT cells. Further we show that AMPK activation by metformin reduced collagen III levels and the ratio of Collagen I to Collagen III. Both AICAR and metformin reduced F-actin and significantly reduced the fiber cross alignment. Our results suggest that PDGFRa signaling may be an important fibrosis target and that activators of AMPK, may be an important therapeutic approach for treating CTS.
| S-EPMC5700922 | biostudies-literature
Project description:Excursion of the median nerve and the surrounding subsynovial connective tissue (SSCT) is diminished in patients with carpal tunnel syndrome (CTS). This study sought to determine if SSCT excursion could be utilized to predict surgical outcome. Idiopathic CTS patients were reviewed with ultrasound and electrodiagnostic tests at baseline. A speckle tracking algorithm was used to determine SSCT relative to tendon motion (shear index). Analysis of variance tests were used to compare SSCT motion with disease severity at baseline. Adjusted linear regressions were used to test the association with patient-reported outcome. A total of 90 CTS patients were analyzed and found to have an average shear index of 79% (95% confidence interval: 76.3%-81.6%). SSCT motion was lower in CTS patients with increasing electrophysiological severity (p = 0.0475). There was no significant association of pre-operative SSCT motion with symptomatic improvement (p = 0.268). Overall, SSCT motion is decreased in CTS patients, but exhibits limited correlation with clinical severity.
| S-EPMC7429249 | biostudies-literature
Project description:ObjectiveTo investigate changes in the median nerve, retinaculum, and carpal tunnel on ultrasound after successful endoscopic carpal tunnel release (ECTR).Materials and methodsThis prospective study involved 37 wrists in 35 patients (5 male, 30 female; mean age ± standard deviation [SD], 56.9 ± 6.7 years) with primary carpal tunnel syndrome (CTS). An in-house developed scoring system (0-3) was used to gauge the clinical improvement after ECTR. Ultrasound was performed before ECTR, and at 1, 3, and 12 months post-ECTR. Changes in the median nerve, flexor retinaculum, and carpal tunnel morphology on ultrasound after ECTR were analyzed. Ultrasound parameters for different clinical improvement groups were compared.ResultsAll patients improved clinically after ECTR. The average clinical improvement score ± SD at 12 months post-ECTR was 2.2 ± 0.7. The median nerve cross-sectional area proximal and distal to the tunnel decreased at all time intervals post-ECTR but remained swollen compared to normal values. Serial changes in the median nerve caliber and retinacular bowing after ECTR were more pronounced at the tunnel outlet than at the tunnel inlet. The flexor retinaculum had reformed in 25 (68%) of 37 wrists after 12 months.ConclusionPostoperative changes in median nerve and retinaculum parameters were most pronounced at the tunnel outlet. Even in patients with clinical improvement after ECTR, nearly all ultrasound parameters remain abnormal at one year post-ECTR. These ultrasound parameters should not necessarily be relied upon to diagnose persistent CTS after ECTR.
| S-EPMC8236373 | biostudies-literature
Project description:The tenosynovium in the human carpal tunnel is connected to the flexor tendons and the median nerve by the subsynovial connective tissue (SSCT). The most common histological finding in carpal tunnel syndrome (CTS), a compression neuropathy of the median nerve, is noninflammatory fibrosis of the SSCT. The relationship, if any, between the fibrosis and nerve pathology is unknown, although some have speculated that a change in the SSCT volume or stiffness might be the source of the compression. Yet, while animal models have been used to study the physiology of nerve compression, so far none have been used to study the relationship of the SSCT pathology to the neurophysiological abnormalities. The purpose of this study was to identify animal models that might be appropriate to study the interaction of SSCT and nerve function in the development of CTS. The front paws of a rat, rabbit, dog, and baboon were dissected. The carpal tunnel anatomy and SSCT of these animals were also examined by light and scanning microscopy and compared to the relevant human anatomy and ultrastructure. The carpal tunnel anatomy and contents of the baboon and rabbit are similar to humans. The canine carpal tunnel lacks the superficial flexor tendons and the rat carpal tunnel is very small. The human, baboon, and rabbit specimens had very similar organization of the SSCT, and content of the carpal canal. We conclude that, while both the baboon and rabbit would be good animal models to study the relationship of the SSCT to CTS, the rabbit is likely to be more practical, in terms of cost and animal care concerns.
| S-EPMC2526031 | biostudies-other
Project description: Not available
| S-EPMC9969978 | biostudies-literature
Project description: Not available
| S-EPMC3414040 | biostudies-literature
Project description:Carpal tunnel syndrome (CTS) is a common peripheral mononeuropathy affecting up to 4% of the general population, typically women in late middle age. The incidence in patients with Fabry disease (FD) is unclear, but may affect 25% of patients with this X-linked lysosomal storage disease. We report three cases of CTS in young Caucasian male patients with classical FD, who developed CTS symptoms with supportive nerve conduction study (NCS) findings. Two patients had bilateral CTS and two had evidence of concurrent ulnar nerve neuropathy on NCS, suggesting a systemic process contributed to nerve compression. All were receiving enzyme replacement therapy (ERT) and had a moderate burden of FD complications. It is possible that an increase in connective tissue in the intracarpal canal in FD patients may be incited by injury to fibroblasts, via either accumulation of globotriaosylceramide (GL3) or local ischaemia through endothelial injury. The former hypothesis may be a more plausible explanation for the development of CTS, as histology of the flexor retinaculae from our patients has demonstrated fibroblasts with characteristic vacuolation and excessive myxomatous stroma, despite endothelial clearance of GL3 in these patients receiving ERT. CTS should not be overlooked in FD patients and young patients presenting with CTS should be evaluated for an underlying systemic or genetic disorder. Surgical carpal tunnel decompression was effective in our patients, already troubled by long-standing acroparesthesia, in providing sustained relief of symptoms.
| S-EPMC3509834 | biostudies-literature
Project description:BackgroundFibroblast behavior and cell-matrix interactions of cells from normal and idiopathic carpal tunnel syndrome (CTS) subsynovial connective tissue (SSCT) with and without Triamcinolone Acetonide (TA) were compared in this study. A cell-seeded gel contraction model was applied to investigate the effect of steroid treatment on SSCT fibroblast gene expression and function.MethodsSSCT cells were obtained from CTS patients and fresh cadavers. Cells were isolated by mechanical and collagenase digestion. Collagen gels (1 mg/ml) were prepared with SSCT cells (1 × 106/mL). A sterile Petri dish with a cloning ring in the center was prepared. The area between the ring and outer dish was filled with cell-seeded collagen solution and gelled for 1 h. The gel was released from the outer way of the petri dish to allow gel contraction. Cell seeded gels were treated with 10 M triamcinolone acetonide (TA) or vehicle (DMSO) in modified MEM. Every 4 h for 3 days the contracting gels were photographed and areas calculated. Duplicate contraction tests were performed with each specimen, and the averages were used in the analyses, which were conducted using two-factor analysis of variance in a generalized linear model framework utilizing generalized estimating equations (GEE) to account for the correlation between samples. The contraction rate was determined by the area change over time, and the decay time constant was calculated. A customized mechanical test system was used to determine gel stiffness and tensile strength. Gene expression was assessed using Human Fibrosis and Cell Motility PCR arrays.ResultsTA-treated gels had a significantly higher contraction rate, tensile strength and stiffness than the untreated gels. Proteinases involved in remodeling had increased expression in TA-treated gels of the patient group. Pro-fibrotic genes and ECM regulators, such as TGF-β, collagens and integrins, were down-regulated by TA, indicating that TA may work in part by decreasing fibrotic gene expression.ConclusionsThis study showed that TA affects cell-matrix interaction and suppresses fibrotic gene expression in the SSCT cells of CTS patients.
| S-EPMC6151186 | biostudies-literature