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The Journal of Neuroscience, December 15, 1999, 19(24):10886-10897
Neurochemical and Cellular Reorganization of the Spinal Cord in a Murine Model of Bone Cancer Pain
Matthew J. Schwei1, 3, Prisca Honore1, 3, Scott D. Rogers1, 3, Janeen L. Salak-Johnson1, 3, Matthew P. Finke1, 3, Margaret L. Ramnaraine2, Denis R. Clohisy2, and Patrick W. Mantyh1, 3 1 Neurosystems Center and Departments of Preventive Sciences, Psychiatry, Neuroscience, and Cancer Center, and 2 Department of Orthopaedic Surgery and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, and 3 Veterans Administration Medical Center, Minneapolis, Minnesota 55417
The cancer-related event that is most disruptive to the cancer patient's quality 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 tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced 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 afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears 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 peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.
Key words: astrocyte; gliosis; nociception; primary afferents; sensitization; osteolysis
Copyright © 1999 Society for Neuroscience 0270-6474/99/192410886-12$05.00/0
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