Acute and chronic stimulation of somatosensory and visceral nociceptors are followed by induction of immediate-early gene (IEG) encoded transcription factors such as Jun, Fos, and Krox proteins in the central nervous system. Transection of a peripheral nerve also results in IEG expression in the axotomized neurons and synaptically related central neurons. The spatial and temporal patterns in the nervous system of IEG expression, as studied by immunohistochemistry, are complex and depend on the type and intensity of noxious stimulation. Immediate-early gene encoded proteins control the transcription of other target genes, a few of which have been identified. The authors hypothesize that activations of IEGs represent steps in the transmission of the noxious afferent input into long-lasting alterations of the neuronal cell program. Thus, stimulation induced changes in gene expression may alter the phenotype of neurons, which implies pathophysiologic modifications of neuron function. Immediate-early gene expression is meaningful beyond its present use in the neurosciences as markers of neuronal activity, because it may provide a clue to the understanding of stimulation-induced pathobiology of the nervous system that is involved in the chronicity of pain.
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