DREAM is a critical transcriptional repressor for pain modulation.
Journal:
Cell 2002 JanAuthors:
Cheng HY, Pitcher GM, Laviolette SR, Whishaw IQ, Tong KI, Kockeritz LK, Wada T, Joza NA, Crackower M, Goncalves J, Sarosi I, Woodgett JR, Oliveira-dos-Santos AJ, Ikura M, van der Kooy D, Salter MW, Penninger JM
Abstract
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
...[more] 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.[less]
Mesh Headings:
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