A New Mouse Model of Complex Regional Pain Syndrome With the Prolonged Pain In Spite of Recovering Skin Inflammation.

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain disorder that usually affects the limbs after injury, surgery or wearing a cast. However, currently, there are no effective treatments or drugs. No animal model mimics these symptoms and shows stable pain-like symptoms for the evaluation of therapeutic drugs. In this study, we developed a new mouse model that showed stable CRPS-like symptoms. METHODS: Male C57BL/6 mice were used for this study. The thigh was tied with a cable tie and 4 days later, the tie was removed. Pain was assessed by measuring licking duration and using von Frey filaments. The skin surface temperatures were measured using a thermography camera. RESULTS: Binding with a cable tie in the thigh induced swelling and inflammation. Three days after the removal of the tie, swelling and inflammation subsided. The duration of licking also increased significantly. Even after the tie was removed, the licking time continued to increase significantly for at least 24 days after its removal. In addition, after removing the tie, mechanical hypersensitivity was induced. Although the skin surface temperature in the leg decreased after cable tie binding, the temperature immediately increased to the level of that of non-treated mice after removing the tie. CONCLUSIONS: Cable tie binding for 4 days induced pain-related behaviours (mechanical hypersensitivity and prolonged licking) without swelling and inflammation of the calves after removal of the tie. Therefore, it is suggested that this mouse model is useful as an animal model that exhibits CRPS-like symptoms. SIGNIFICANCE STATEMENT: Previous animal models of complex regional pain syndrome (CRPS) did not show long-term pain-like symptoms. In this study, we developed an animal model that exhibited long-term pain-like symptoms without skin symptoms by tying a cable tie to the hind thigh with a constant force. This animal model is expected to be useful not only for elucidating the mechanism of CRPS development but also for drug development.