Pain transmission in the spinal cord is regulated by a balance of facilitatory and inhibitory influences operating on the neural circuits of the somatosensory system. The transcriptional repressor DREAM acts constitutively to suppress prodynorphin expression in spinal cord neurons. Knocking out DREAM results in sufficient dynorphin expression to produce a strong reduction in generalized pain behavior, highlighting the role that intracellular molecules play in modulating pain gating in the spinal cord.