Transcutaneous application of carbon dioxide improves contractures after immobilization of rat knee joint

Abstract

Joint contractures are a major complication following joint immobilization. However, no fully effective treatment has yet been found. Recently, carbon dioxide (CO2) therapy was developed and verified this therapeutic application in various disorders. We aimed to verify the efficacy of transcutaneous CO2 therapy for immobilization-induced joint contracture. Method: Twenty-two Wistar rats were randomly assigned to three groups: caged control, those untreated after joint immobilization, and those treated after joint immobilization. The rats were treated with CO2 for 20 min once a daily either during immobilization, (prevention) or during remobilization after immobilization (treatment). Knee extension motion was measured with a goniometer, and the muscular and articular factors responsible for contractures were calculated. We evaluated muscle fibrosis, fibrosis-related genes (collagen Type 1α1 and TGF-β1) in muscles, synovial intima's length, and fibrosis-related proteins (Type I collagen and TGF-β1) in the joint capsules. Results: CO2 therapy for prevention and treatment improved the knee extension motion. Muscular and articular factors decreased in rats of the treatment group. The muscular fibrosis of treated rats decreased in the treatment group. Although CO2 therapy did not repress the increased expression of collagen Type 1α1, the therapy decreased the expression of TGF-β1 in the treatment group. CO2 therapy for treatment improved the shortening of the synovial membrane after immobilization and decreased the immunolabeling of TGF-β1 in the joint capsules. Conclusions: CO2 therapy may prevent and treat contractures after joint immobilization, and appears to be more effective as a treatment strategy for the deterioration of contractures during remobilization.

Local application of a transcutaneous carbon dioxide paste prevents excessive scarring and promotes muscle regeneration in a bupivacaine‐induced rat model of muscle injury

“…In the CO 2 group, TGF‐β expression was lower than that in the control group during the second half of the experiment, suggesting that this may have led to reduced scarring. In a previous study, CO 2 therapy was shown to reduce TGF‐β1 protein levels in joint capsules associated with fibrosis and improve the passive range of motion in a rat model 28 . Here, the CO 2 paste significantly prevented fibrosis during muscle regeneration, which was likely due to the early downregulation of TGF‐β, a major trigger of the fibrosis cascade.…”

“…In a previous study, CO 2 therapy was shown to reduce TGF‐β1 protein levels in joint capsules associated with fibrosis and improve the passive range of motion in a rat model. 28 Here, the CO 2 paste significantly prevented fibrosis during muscle regeneration, which was likely due to the early downregulation of TGF‐β, a major trigger of the fibrosis cascade. In addition, fibrin induces the expression of inflammatory chemokines and cytokines that promote muscle degeneration, such as IL‐6 and IL‐1β.…”

Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma

“…We have developed a new transcutaneous CO 2 application system using 100% CO 2 gas and a transdermal CO 2 absorption-enhancing hydrogel [16]. This treatment has been used previously in several animal models, and it can increase local blood flow, prevent muscle atrophy and contraction, and recover muscle damage [18][19][20][21][22][23]. Oe et al demonstrated similar changes to those that occur within muscles when aerobic exercise is performed [23].…”

“…Carbon dioxide (CO 2 ) therapy is widely known as an effective treatment to improve blood flow and has been indicated for various diseases such as heart disease and skin conditions [16]. We demonstrated that transcutaneous application of CO 2 could improve local blood flow and promote the suppression of muscle atrophy and contraction, as well as the recovery of muscle damage [17][18][19][20][21][22][23]. However, while we have demonstrated the effect of transcutaneous application of CO 2 in suppressing tumor growth [24], we have not demonstrated the effect of cancer cachexia.…”