Immediate-early genes in the nervous system-are they involved in mechanisms of chronic pain?

Evidence suggests that long-term changes in the nervous system may represent a cause of chronic pain. Recent processes became accessible at the cellular level of the nervous system by analyzing immediate-early genes (IEG). The nuclear proteins encoded by these genes function as transcription factors, i.e. they control the expression of other genes. Many conditions of physiological and pathological stimulation can activate IEGs in the nervous system, and these findings have led to the concept of "stimulation-transcription-coupling". Noxious stimuli such as electrical C-fibre stimulation, noxious skin heating or subcutaneous formalin injection result in the transsynaptic induction of the IEG encoded proteins c-Fos, C-Jun and Krox-24, in the dorsal horn of the spinal cord. Non-noxious stimuli usually fail to induce the expression of IEGs. Nerve lesions result in a selective expression of C-Jun protein in the axotomized nerve cells, both in the peripheral and central nervous systems. Expression of IEGs after noxious stimuli and nerve lesions last for days or weeks, indicating profound alterations in the biochemistry and function of nerve cells. These changes could be involved in central nervous mechanisms of chronic pain.