Genetic analysis of pain mechanisms.

Pain is the major reason for visits to the doctor. It is a complex sensation, with both a sensory and an emotional component. Its detailed regulation at all levels of the central nervous system, from the periphery to the cortex, has hindered our understanding of the neurobiological basis of pain. Furthermore, injury can produce long-lasting changes in pain pathways and chronic pain. The recent use of genetically modified organisms has significantly advanced our comprehension of the molecular and cellular mechanisms underlying pain. In this article we present the current state of knowledge regarding pain transmission, modulation, and plasticity, and some of the contributions made by studies of genetically altered mice. The cellular mechanisms explaining observed phenotypes, the involvement of supraspinal areas, and the plasticity underlying chronic pain are the three areas just beginning to be explored.