1Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, China
2Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China
# These authors contribute to this work equally

Abstract 

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 VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.

Keywords

Cancer-induced pain; Microglia; Spinal dorsal horn; Toll-like receptor 4; Voltage-dependent anion channel 1

[SpringerLink]