Pain genes?: Natural variation and transgenic mutants

Like many other complex biological phenomena, pain is starling to be studie d at the level of the gene. Advances in molecular biological technology hav e allowed the cloning, mapping, and sequencing of genes, and also the ablil ity to disrupt their function entirely (i.e. via transgenic knoockouts). Wi th these new tools at hand, pain researchers have begun in earnest the task of defining (a) which of the 70,000-150,000 mammalian genes are involved i n the mediation of pain, and (b) which of the pain-relevant genes are polym orphic, contributing to both natural variation in responses and pathology. Although there are only a few known examples in which single gene mutations in humans are associated with pain conditions (e.g. an inherited form of m igraine and congenital insensitivity to pain), it is likely that others wil l be identified. Concurrently, a variety of genes have been implicated in b oth the transmission and control of "pain" messages in animals. The present review summarizes current progress to these ends, focusing on both transge nic (gene-->behavior) and classical genetic (behavior-->gene) approaches in both humans and laboratory mice.