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Abstract Background The study aimed to investigate the effect of low-frequency electrical stimulation (LFES) on disuse muscle atrophy and its mechanism in a rabbit model of knee extension contracture. Methods This study involved two experiments. In the time-point experiment, 24 rabbits were randomly divided into 4 groups: Control 1 (Ctrl1 group), immobilization for 2 weeks (I-2 group), immobilization for 4 weeks (I-4 group), and immobilization for 6 weeks (I-6 group). In the intervention experiment, 24 rabbits were randomly divided into 4 groups: Control 2 (Ctrl2 group), electrical stimulation (ESG group), natural recovery (NRG group), and electrical stimulation treatment (ESTG group). All intervention effects were assessed by evaluating the knee joint range of motion (ROM), cross-sectional area (CSA) of the rectus femoris muscle, and expression of autophagy-related proteins. Results The time-point experiment showed that immobilization reduced the knee ROM, reduced the rectus femoris muscle CSA, and activated autophagy in skeletal muscle. The levels of five autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), autophagy-related protein 7 (Atg7), p62, and microtubule-associated protein light chain 3B-II (LC3B-II)] were significantly elevated in the skeletal muscle of the I-4 group. The intervention experiment further showed that LFES significantly improved the immobilization-induced reductions in ROM and CSA. Additionally, LFES resulted in a significant decrease in the protein expression of mTOR, p-mTOR, Atg7, p62, and LC3B-II in the rectus femoris muscle. Conclusions LFES alleviates immobilization-evoked disuse muscle atrophy possibly by inhibiting autophagy in the skeletal muscle of rabbits.

The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future. Keywords: Immobilization-induced joint contracture, Disuse skeletal muscle atrophy, Skeletal muscle fibrosis, Treatment

Objective: The purpose of this study was to examine the intervention effect of radial extracorporeal shock wave combined with ultrashort wave diathermy on immobilization-induced fibrosis and contracture of muscle. Design: The groups included male rabbits for the group (control group). To cause joint contracture, rabbits underwent plaster fixation of a left knee joint at full extension. After immobilization for 4 wks, all rabbits were randomly divided into five groups: model group, natural recovery group, radial extracorporeal shock wave treatment group, ultrashort wave diathermy group, and radial extracorporeal shock wave combined with ultrashort wave diathermy group. All intervention effects were assessed by evaluating the cross-sectional area and the collagen deposition of muscle, the knee joint range of motion and the protein levels for transforming growth factor β1 and hypoxia-inducible factor 1α. Results: The combined treatment group got the best recovery of the knee joint function. The combined treatment was more effective than radial extracorporeal shock wave or ultrashort wave diathermy alone against the fibrosis and contracture of muscle, as well as the overexpression of transforming growth factor β1 and hypoxia-inducible factor 1α. Conclusions: Radial extracorporeal shock wave combined with ultrashort wave diathermy was effective in alleviating immobilization- induced contracture and fibrosis of muscle, as well as reducing the molecular manifestations of muscle fibrosis. [ABSTRACT FROM AUTHOR]