Abstract

Cryotherapy is commonly used in the treatment of skeletal muscle injuries. However, the data to support the use of cryotherapy is inconclusive, and the biochemical etiology of cryotherapy in human skeletal muscle remains largely unknown. We therefore sought to determine how a clinically-relevant dose of cryotherapy would impact the transcriptome and metabolome of skeletal muscle. Eight healthy male subjects (age 24.7 ± 4.5 years, BMI 22.2 ± 1.6) received a 15 minute bout of local cryotherapy, delivered via ice cup massage over the anterolateral thigh. This resulted in an 85% decrease in skin temperature and a predicted 27% reduction in intramuscular temperature. The contralateral side served as a non-treated control. Two hours after cryotherapy, muscle biopsies were obtained to analyze changes in the transcriptome, metabolome, and activation of p38 MAPK, ERK1/2, Akt, and p70S6K proteins. No changes were detected in the transcriptome between control and cooled muscles. Cryotherapy reduced levels of hexose sugars and hypoxanthine by 1.3%, but no statistically different changes were observed in 60 additional metabolites. Overall, no differences in phosphorylated p38 MAPK, ERK1/2, Akt, and p70S6K were observed. A clinically relevant dose of cryotherapy produced negligible acute biochemical and molecular changes in the skeletal muscle of human subjects.

Highlights

  • Skeletal muscle injuries are among the most prevalent types of injuries observed in the sports medicine setting[1]

  • The combined results from this work indicate that a single dose of cryotherapy, administered following standard of care guidelines, has a negligible acute impact on gene expression, cellular metabolism, and signal transduction pathways important in muscle growth and metabolism

  • Local cryotherapy is where ice or cold packs are administered to a specific region of a limb or defined area on the trunk or head

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Summary

Introduction

Skeletal muscle injuries are among the most prevalent types of injuries observed in the sports medicine setting[1]. Based on the proposed mechanisms of action of cryotherapy and previous studies in animal models, and the involvement of cold shock genes in muscle hypertrophy, we hypothesized that a single therapeutic application of cold would result in wide-spread changes in the metabolome and transcriptome of muscle tissue, and activate the Akt and p70S6K signaling pathways. To test this hypothesis, we used a paired design in healthy subjects where we administered a clinically relevant dose of cryotherapy to one leg, while the other leg served as a control. Biopsies were obtained from the treated and untreated muscles, and subjected to biochemical and molecular analyses

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