Using c-fos as a neural marker of pain

Just over a decade has past since Hunt et al. reported that the gene c-fos and its protein product Fos are expressed in the spinal cord of rats subjected to peripheral noxious stimulation. These authors showed that noxious stimulation (application of radiant heat or mustard oil) to the hind paw resulted in a massive increase in the expression of Fos in neurons in the dorsal horn of the lumbar spinal cord. Since then, there has been an explosion of studies in which c-fos has been used to study nociception (pain), and the number of such studies increases each year. The net result has been to establish c-fos expression as a valuable tool in pain research. Moreover, recent studies have provided evidence identifying the role of c-fos expression in spinal nociceptive processes. However, there are several important limitations to the practice of using c-fos to study nociception, and these limitations can be easily overlooked as the practice graduates to the status of an established technique. The increasing use of c-fos to study nociception necessitates a critical review of the practice, identifying the shortcomings as well as the strengths of this tool.