Advances in our understanding of the activation of peripheral damage-sensing neurons (nociceptors) over the past year have been complemented by electrophysiological and imaging studies of central nervous system pain-related centres. The manipulation of gene expression in a reversible and cell type specific way combined with imaging and electrophysiological studies holds promise for helping us to identify the spatial and molecular substrates of pain perception with increasing precision and gives hope for improved analgesic therapies.