The aim of this investigation was to determine whether murine models of inflammatory, neuropathic and cancer pain are each characterized by a unique set of neurochemical changes in the spinal cord and sensory neurons. All models were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviorally characterized. A variety of neurochemical markers that have been implicated in the generation and maintenance of chronic pain were then examined in spinal cord and primary afferent neurons. Three days after injection of complete Freund's adjuvant into the hindpaw (a model of persistent inflammatory pain) increases in substance P, calcitonin gene- related peptide, protein kinase Cγ, and substance P receptor were observed in the spinal cord. Following sciatic nerve transection or L5 spinal nerve ligation (a model of persistent neuropathic pain) significant decreases in substance P and calcitonin gene-related peptide and increases in galanin and neuropeptide Y were observed in both primary afferent neurons and the spinal cord. In contrast, in a model of cancer pain induced by injection of osteolytic sarcoma cells into the femur, there were no detectable changes in any of these markers in either primary afferent neurons or the spinal cord. However, in this cancer-pain model, changes including massive astrocyte hypertrophy without neuronal loss, increase in the neuronal expression of c- Fos, and increase in the number of dynorphin-immunoreactive neurons were observed in the spinal cord, ipsilateral to the limb with cancer. These results indicate that a unique set of neurochemical changes occur with inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further suggest that cancer induces a unique persistent pain state. Determining whether these neurochemical changes are involved in the generation and maintenance of each type of persistent pain may provide insight into the mechanisms that underlie each of these pain states. (C) 2000 IBRO.
Bibliographical noteFunding Information:
This work was supported by a Merit Review from the Veterans Administration, NIH grants NS23970, AG11852, DA11986, NIDCR training grant DEO7288, the Roby C. Thompson, Jr. Endowment in Musculoskeletal Oncology, DSA training grant DE00270, and a grant from the Academic Health Center Strategic Initiative. We would like to thank Dr R. Elde for the generous gift of the dynorphin antibody and Dr J. Pomonis for his helpful comments.
Copyright 2007 Elsevier B.V., All rights reserved.
- Astrocyte hypertrophy
- Persistent pain
- c-Fos protein