Our results showed that the application of clinical-like cryotherapy in mice with acute knee arthritis reduced inflammatory signs and improved pain, joint swelling, motor coordination and balance.
The inflammatory signs (neutrophil migration, cytokines and joint inflammation) analyzed in our study are related to the systemic inflammatory response of arthritis (19, 20). The experimental model of AIA is a suitable and reproducible experimental model that exhibits a number of histopathological findings similar to those observed in human rheumatoid arthritis (4, 12).
One of the beneficial effects of cryotherapy was the decline in neutrophil migration to the synovial fluid. High neutrophil levels are found in human arthritic joints, especially in the joint synovial fluid, with significant potential to inflict damage directly to tissue, bone and cartilage through the secretion of proteases and metabolites, as well as stimulate inflammation via the secretion of cytokines, chemokines, prostaglandins and leukotrienes(21, 22, 23, 24). The decline in neutrophil migration was accompanied by a decrease in IL-1β, IL-6 and TNF-α cytokine levels in the synovial fluid, demonstrating the beneficial effect of the clinical-like cryotherapy protocol used to control acute joint inflammation. Levels of these cytokines are known to rise in the early stages of arthritis and fall during regression(25, 26). Histological analysis revealed that cryotherapy also improved the inflammatory picture by reducing leukocyte infiltration and thickening the synovial membrane.
In addition to the aforementioned inflammatory signs, the presence of pain and swelling are also characteristic of arthritis. Our results also showed the beneficial effects of clinical-like cryotherapy in reducing pain and joint swelling. The pain resulting from the antigen-induced challenge in mice depends on a cytokine cascade(15). Joint swelling, caused by the release of inflamed synovium through the cells of local blood vessels, is common in different types of arthritis ( 27, 28).
Two cryotherapy sessions (20 min every 2 hours) improved inflammatory signs, decreased pain and swelling, and enhanced the motor coordination and balance of the animals in the acute phase of arthritis. Cryotherapy has been used in the clinical rehabilitation of patients with post-sports injury arthritis, reducing joint pain, swelling, degeneration and inflammation(29, 30, 31). Our study provides a new scientific contribution on the benefits of clinical-like cryotherapy in the treatment of acute knee arthritis in an animal model. It is also used empirically as a complementary treatment for rheumatoid arthritis, with a good tolerance profile when compared to corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs); however, the protocols have not been standardized(7).