Genetic Approaches for the Study of Pain

Abstract

The development of gene technology has opened unprecedented new perspectives in the understanding as well as the treatment of medical disorders. Although molecular techniques and genetic engineering were introduced into the pain field with a significant delay, as compared with other areas in neuroscience, they are now regarded as the prime methods for addressing mechanisms which underly cellular and network changes causing chronic pain. It is now not only possible to delete or to overexpress pain-associated molecules, but also feasible to bring about these changes selectively in distinct anatomical compartments of the pain pathway. At the very forefront is the method of conditional gene deletion using the Cre-loxP system in transgenic mice. This remains by far the most robust and clean approach for selective modification of gene expression. Some limitations of the Cre-loxP system in mice are now being overcome by novel approaches such as RNA interference. Moreover, RNA- and DNA viruses are emerging as excellent tools for delivering genes or deleting them in distinct regions in the pain pathway. Not only do these methodologies offer means for rapidly testing a large number of candidate molecules for their potential functions in pain, but they also allow, for the first time, a possibility of moving gene technology out of the laboratory straight to the bedside of chronically pain-afflicted patients.