Chronic pain has an enormous impact on the quality of life for billions of patients, families, and caregivers worldwide, and current therapies do not adequately address pain for most patients. A basic understanding of the conserved genetic framework controlling pain may help us develop better, non-addictive pain therapies. Here we combine human GWAS signals for chronic pain with functional screening of candidate pain genes in the fly in order to identify new analgesic targets. From these efforts we describe 56 druggable conserved pain genes for further consideration. This included dAcsl, a fatty acid-metabolizing enzyme that is conserved through to humans and shows association with clinical pain. dAcsl knockdown and mutant larvae showed delayed nocifensive responses to localised and global noxious heat. Mechanistically, knockdown of dAcsl reduced dendritic branching of nociceptive neurons, and the pain phenotype in these animals can be rescued through dietary intervention. Ultimately, our approach combining human and fly genomics to guide discovery of novel pain targets has yielded a better basic understanding of pain biology and can guide development of new pain therapies.