Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain

The cancer-related event that is most disruptive to the cancer patient's qu ality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tu mor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there w as a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal ho rn. Additionally, normally non-noxious palpation of the bone with cancer in duced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferent s were positively correlated with the extent of bone destruction and the gr owth of the tumor. This "neurochemical signature" of bone cancer pain appea rs unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into per ipheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.