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Bone pain associated with advanced tumor metastasis is the most severe threat to life quality of patients. Highly efficient and low-toxic therapeutics is of urgent need for this complication. Bone tumor metastasis was established by direct bone inoculation of Walker 256 mammary gland carcinoma cells. Bone nociception was measured by mechanical allodynia, thermal hyperalgesia and spontaneous flinches. P2X7R level was determined by immunoblotting. The inward current was recorded by a patch clamp. The related cytokines were determined by ELISA. Our results showed that teniposide (TN) treatment significantly ameliorated bone nociception associated with tumor inoculation to a comparable extent with P2X7-specific inhibitor, BBG, in rat model. The efficient blockade of inward current generation and pro-inflammatory cytokines secretion were observed upon administration with TN. Our data highlighted the therapeutic potency of TN in this complication associated with tumor metastasis and warrants further clinical investigations.