Although
bone cancer pain can be severe and is relatively common, very little is known about the basic mechanisms that generate and maintain this debilitating
pain. To begin to define the mechanisms that give rise to
bone cancer pain, a mouse model was developed using the intramedullary injection and containment of osteolytic
sarcoma cells in the mouse femur. These
tumor cells induced bone destruction as well as ongoing and movement-evoked
pain behaviors similar to that found in patients with
bone cancer pain. In addition, there was a significant reorganization of the spinal cord that received sensory input from the cancerous bone, and this reorganization was significantly 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 pain, we targeted excessive osteoclast activity using
osteoprotegerin, a secreted decoy receptor that inhibits osteoclast activity.
Osteoprotegerin blocked excessive
tumor-induced, osteoclast-mediated bone destruction, and significantly reduced ongoing and movement-evoked
pain, and the neurochemical reorganization of the spinal cord. These data suggest that this model can provide insight into the mechanisms that generate
bone cancer pain and provide a platform for developing and testing novel
analgesics to block
bone cancer pain.