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Objective The biological mechanisms of cryotherapy for managing acute pain remain unclear. Additionally, it is unknown whether the effectiveness of cryotherapy depends on the applied temperature. This study aimed to clarify the biological effects of cryotherapy and to examine the therapeutic effects of cryotherapy applied at different temperatures in rats. Methods This was an experimental study using a rat knee joint arthritis model. Thirty-five Wistar rats were randomly divided into arthritis (AR), arthritis with 5°C cryotherapy (CR-5), arthritis with 10°C cryotherapy (CR-10), and sham-arthritis control (CON) groups. Arthritis was induced by injecting a mixture of kaolin/carrageenan into the right knee joint. Cryotherapy was applied for 7 days starting the day after injection by immersing the right knee joint in 5°C or 10°C water. Joint transverse diameter, pressure pain threshold, and pain-related behaviors were assessed for 7 days. The number of CD68-positive cells in the knee joint and the expression of calcitonin gene-related peptide in the spinal dorsal horn 8 days after injection were analyzed by immunohistochemical staining. Results Improvements in transverse diameter, pressure pain threshold, and pain-related behaviors were observed in the CR-5 and CR-10 groups on the 3rd day compared with the AR group. The number of CD68-positive cells and the expression of calcitonin gene-related peptide in the CR-5 and CR-10 groups were significantly decreased compared with the AR group. There were no significant differences in all results between the CR-5 and CR-10 groups. Conclusions Cryotherapy can ameliorate inflammatory pain through reduction of synovium and central sensitization. Additionally, the effects of cryotherapy lower than 10°C are observed independent of applied temperature. Impact Cryotherapy may be beneficial as a physical therapy modality for pain and swelling management in the acute phase of inflammation. Translational human study is needed to determine the effective cryotherapy temperature for the inflammatory pain.

Effects of Cryotherapy Applied at Different Temperatures on Inflammatory Pain During the Acute Phase of Arthritis in Rats