Cryotherapy suppresses tendon inflammation in an animal model

Cryotherapy (or cold treatment) has been a popular treatment to relieve pain caused by injuries to tissues such as tendons. However, the exact mechanisms behind the beneficial effects of cryotherapy in tendons remain largely unclear. As prostaglandin E₂ (PGE₂) is known to be a major mediator of acute inflammation in tissues, which is related to tissue pain, we hypothesized that the beneficial effects of cryotherapy in tendons are mediated by downregulation of PGE₂ levels. To test this hypothesis, we applied cold treatment to mouse patellar and Achilles tendons using two animal models: exhaustive mouse treadmill running and acute mouse tendon injury by needle penetration. We then measured the levels of PGE₂ and protein expression levels of COX-2, an enzyme responsible for PGE₂ production in tissues, under both experimental conditions. We found that treadmill running increased PGE₂ levels in both patellar and Achilles tendons compared to control mice without running. Cold treatment for 30 min after treadmill running was sufficient to reduce PGE₂ levels to near baseline control levels in both tendons. An extension of cold treatment to 60 min resulted only in a marginal decrease in patellar tendons, but a marked decrease in Achilles tendons. Moreover, COX-2 protein levels in both tendons were also lowered by cold treatment, suggesting that the reduction of PGE₂ levels in tendons by cold treatment is at least in part due to the decreased COX-2 expression. Similarly, in the acutely injured tendons, 30 min of cold treatment after needle penetration reduced PGE₂ levels when compared to the controls at room temperature (22°C). This decrease was sustained up to at least 3 h after the administration of cryotherapy. Given that PGE₂ is a known pain sensitiser, the results of this study suggest that the ability of cold treatment to reduce pain may be attributable to its ability to decrease PGE₂ production in tendons.