Etanercept attenuates thermal and mechanical hyperalgesia induced by bone cancer

Bone cancer pain commonly occurs when tumors originating in the breast, prostate or lung metastasize to long bones, spinal vertebrae and/or the pelvis. However, the underlying mechanisms of bone cancer pain remain largely unknown. The present study aimed to determine the role of spinal tumor necrosis factor-α (TNF-α) in the development of bone cancer pain. Osteosarcoma NCTC 2472 cells were implanted into the femoral intramedullary space of C3H/HeJ mice to establish a bone cancer model. Resulting pain-related behaviors, namely spontaneous foot lifting, paw withdrawal mechanical threshold and paw withdrawal thermal latency were observed prior to inoculation and on days 3, 5, 7, 10 and 14 thereafter. Reverse transcription-quantitative polymerase chain reaction was also performed to assess the levels of TNF-α mRNA within the spinal cord. In addition, the effects of the TNF-α antagonist etanercept on TNF-α levels and pain behaviors were evaluated. It was observed that the levels of TNF-α mRNA in the spinal cord were significantly higher in tumor-bearing mice 10 days post-inoculation, which was accompanied by increases in spontaneous flinching, mechanical hyperalgesia and thermal hyperalgesia, relative to control mice. Etanercept attenuated the bone cancer-induced increase in TNF-α and pain-related behaviors. These results suggest that etanercept may be a potential therapeutic for the treatment of bone cancer pain.