Voltage-dependent anion channel 1 (VDAC1) is thought to contribute to the progression of tumor development.However,whether VDAC1 contributes to bone cancer pain remains unknown.In this study,we found that the expression of VDAC1 was upregulated in the L2-5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity.Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4 (TLR4).Intrathecal injection of minocycline,an inhibitor of microglia,also attenuated the pain hypersensitivity of rat models of bone cancer pain.These results suggest that VDACl plays a significant role in the development of complicated cancer pain,possibly by regulating the expression of TLR4.