Abstract: Objective To investigate the effect of Sophoridine in mice with bone cancer pain (BCP) and its mechanism. Methods A total of 24 C57BL/6 mice were randomly divided into sham surgery group (Sham group), bone cancer pain group (BCP group), bone cancer pain+normal saline group (BCP+NS group), and bone cancer pain+Sophoridine group (BCP+Sophoridine group, 25 mg/kg). The mechanical paw withdrawal threshold and the paw withdrawal latency were detected at 1 d before and 3 d, 5 d, 7 d, 10 d and 14 d after cancer cell inoculation. The expression levels of dorsal root ganglion of spinal cord L4⁃L5 segment and DAP12/Trem2/TLR4 axis⁃related proteins in the cerebral cortex tissues were determined by Western blot. Results Compared with the Sham group, the mechanical paw withdrawal threshold and the paw withdrawal latency in the BCP group were significantly reduced at 5 d, 7 d, 10 d and 14 d after surgery (all P<0.05).Compared with the BCP group, the paw withdrawal latency in the BCP+Sophoridine group was significantly increased at 5 d, 7 d, 10 d, and 14 d after surgery (all P<0.05), while the mechanical paw withdrawal threshold was significantly increased in the BCP+Sophoridine group at 10 d and 14 d after surgery (all P<0.05). Western blot results showed that compared with the BCP group, the protein expressions of TLR4 in both dorsal root ganglion and cerebral cortex tissues of mice in the BCP+Sophoridine group were significantly reduced (all P<0.05), and the protein expressions of DAP12 and Trem2 were significantly increased (all P<0.05). Conclusions Sophoridine can alleviate bone cancer pain, and the underlying mechanism may be related to the DAP12/Trem2/TLR4 axis.

Key words:  Sophoridine, Bone cancer pain, DAP12/Trem2/TLR4 axis, Behavior, Mice