Molecular genetic approaches to nociceptor development and function.

The activation of peripheral nociceptors is the subject of intense scrutiny, because of its significance in pain regulation. Genetic approaches, including homology cloning, difference cloning and transgenic manipulation of mice are providing useful insights into nociceptor function. Recent work suggests that transcriptional regulators (for example, islet-I), which are expressed relatively selectively in sensory neurones, play a crucial role in defining cellular phenotype. Difference cloning has identified genes which encode both ligand-gated and voltage-gated ion channels expressed by small-diameter sensory neurones. The role of inflammatory mediators such as NGF in regulating nociceptor function has been clarified in mis-expression and deletion studies. An understanding of the mechanisms that regulate gene expression in nociceptors should provide new ways to manipulate nociceptor sensitivity, with potential significance for pain therapy.