Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons

The aim of this investigation was to determine whether murine models of inf lammatory, neuropathic and cancer pain are each characterized by a unique s et of neurochemical changes in the spinal cord and sensory neurons. All mod els were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviora lly characterized. A variety of neurochemical markers that have been implic ated in the generation and maintenance of chronic pain were then examined i n 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, calciton in gene-related peptide, protein kinase C gamma, and substance P receptor w ere 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 neuron s and the spinal cord. In contrast, in a model of cancer pain induced by in jection of osteolytic sarcoma cells into the femur, there were no detectabl e 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 expr ession of c-Fos, and increase in the number of dynorphin-immunoreactive neu rons were observed in the spinal cord, ipsilateral to the limb with cancer. These results indicate that a unique set of neurochemical changes occur wit h inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further sug gest that cancer induces a unique persistent pain state. Determining whethe r these neurochemical changes are involved in the generation and maintenanc e of each type of persistent pain may provide insight into the mechanisms t hat underlie each of these pain states. (C) 2000 IBRO. Published by Elsevie r Science Ltd. All rights reserved.