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

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, in cluding the deletion or transcriptional inhibition of which produces altera tions in behavioral responses on nociceptive assays; those the transcriptio n of which is selective to pain-relevant anatomic loci (eg, small-diameter cells of the dorsal root ganglion); those the transcription of which is enh anced in animals experiencing tonic nociception or hypersensitivity states; and, finally, those existing in polymorphic forms relevant to interindivid ual variability. The purpose of this review is to compare the utility of va rious bottom-up and top-down approaches in defining, identifying, and study ing pain genes. We will focus on 4 major techniques: transgenic knockouts, antisense knockdowns, gene expression assays (including DNA microarray-base d expression profiling), and linkage mapping.