Abstract
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.