Identifying pain genes: Bottom-up and top-down approaches

Abstract

A major goal of pain research at the present time is the identification of pain genes. Such genes have been informally defined in a number of ways, including the deletion or transcriptional inhibition of which produces alterations in behavioral responses on nociceptive assays; those the transcription of which is selective to pain-relevant anatomic loci (eg, small-diameter cells of the dorsal root ganglion); those the transcription of which is enhanced in animals experiencing tonic nociception or hypersensitivity states; and, finally, those existing in polymorphic forms relevant to interindividual variability. The purpose of this review is to compare the utility of various bottom-up and top-down approaches in defining, identifying, and studying pain genes. We will focus on 4 major techniques: transgenic knockouts, antisense knockdowns, gene expression assays (including DNA microarray-based expression profiling), and linkage mapping.