Bone cancer pain: From mechanism to model to therapy

Although bone cancer pain can be severe and is relatively common, very litt le is known about the basic mechanisms that generate and maintain this debi litating pain. To begin to define the mechanisms that give rise to bone can cer pain, a mouse model was developed using the intramedullary injection an d containment of osteolytic sarcoma cells in the mouse femur. These tumor c ells induced bone destruction as well as ongoing and movement-evoked pain b ehaviors similar to that found in patients with bone cancer pain. In additi on, there was a significant reorganization of the spinal cord that received sensory input from the cancerous bone, and this reorganization was signifi cantly different from that observed in mouse models of chronic neuropathic or inflammatory pain. To determine whether this mouse model of bone cancer could be used to define the basic mechanisms giving rise to bone cancer pai n, we targeted excessive osteoclast activity using osteoprotegerin, a secre ted decoy receptor that inhibits osteoclast activity. Osteoprotegerin block ed excessive tumor-induced, osteoclast-mediated bone destruction, and signi ficantly reduced ongoing and movement-evoked pain, and the neurochemical re organization of the spinal cord. These data suggest that this model can pro vide insight into the mechanisms that generate bone cancer pain and provide a platform for developing and testing novel analgesics to block bone cance r pain.