DREAM is a critical transcriptional repressor for pain modulation.
Control and treatment of chronic pain remain major clinical challenges. Progress may be facilitated by a greater understanding of the mechanisms underlying pain processing. Here we show that the calcium-sensing protein DREAM is a transcriptional repressor involved in modulating pain. dream(-/-) mice displayed markedly reduced responses in models of acute thermal, mechanical, and visceral pain. dream(-/-) mice also exhibited reduced pain behaviors in models of chronic neuropathic and inflammatory pain. However, dream(-/-) mice showed no major defects in motor function or learning and memory. Mice lacking DREAM had elevated levels of prodynorphin mRNA and dynorphin A peptides in the spinal cord, and the reduction of pain behaviors in dream(-/-) mice was mediated through dynorphin-selective kappa (kappa)-opiate receptors. Thus, DREAM appears to be a critical transcriptional repressor in pain processing.
Pubmed ID: 11792319 RIS Download
Animals | Base Sequence | Behavior, Animal | Calcium-Binding Proteins | Cells, Cultured | Consensus Sequence | Down-Regulation | Enkephalins | Heart | Hyperalgesia | Inflammation | Kv Channel-Interacting Proteins | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | Neuralgia | Neurons | Physical Stimulation | Presenilin-1 | Presenilin-2 | Protein Precursors | Proto-Oncogene Proteins c-fos | Receptors, N-Methyl-D-Aspartate | Receptors, Opioid, kappa | Repressor Proteins | Spinal Cord | Stimulation, Chemical | Transcription, Genetic