Cryotherapy and Duration of Inflammatory Pain in Mice

Background: Cryotherapy, or icing, is ubiquitously employed and recommended for managing acute inflammation and the pain that accompanies it. Recently published data has suggested that pharmacological reduction of inflammation, despite the short-term benefit of pain relief, has a longer-term risk of delaying the resolution of pain and increasing the risk of pain chronification. Methods: Whether cryotherapy would similarly lead to delayed pain resolution was tested in mice given either complete Freund’s adjuvant into the hind paw or subjected to an exerciseenhanced pain assay whereby hypotonic saline was injected into the gastrocnemius muscle before and after wheel running. Mice were tested for tactile pain thresholds before and at multiple time points after injury. Results: Cryotherapy, applied over three days using different timing protocols, was observed to prolong the duration of pain behavior by approximately two-fold, from ~15 days to >30 days. Neutrophil injection into the hind paw was found to prevent the pain chronification caused by cryotherapy. Alternate therapies, including heat, menthol, and contrast therapy (alternating heat and cold) did not affect pain resolution. Conclusions: We conclude that, similar to steroid and non-steroidal anti-inflammatory drugs, the use of cryotherapy should be reconsidered for the management of acute inflammatory injury.