Behavioural tests
All behavioural tests were performed 24 h after administration (days 2, 5, 9, 12, 16, 19, 23, and 26). The thermal nociceptive threshold was assessed using the ZH-6C cold-plate (Anhui Zhenghua Biological Instrument Equipment Co., Ltd.). The mice were placed on the cold-plate floor. The temperature of the cold plate was kept constant at 4.0-4.2 °C. After allowing the mice to adapt for 1 min, the frequency of hind-paw licking by the mice was recorded for 2 min.