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 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Behavior, Animal / physiology
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Calcium-Binding Proteins*
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Cells, Cultured
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Consensus Sequence
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Down-Regulation / physiology
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Enkephalins / genetics
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Enkephalins / metabolism
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Heart / physiology
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Hyperalgesia / physiopathology
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Inflammation / physiopathology
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Kv Channel-Interacting Proteins
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neuralgia / immunology
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Neuralgia / physiopathology*
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Neurons / cytology
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Neurons / physiology
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Physical Stimulation
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Presenilin-1
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Presenilin-2
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Protein Precursors / genetics
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Protein Precursors / metabolism
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, Opioid, kappa / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism*
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Spinal Cord / cytology
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Stimulation, Chemical
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Transcription, Genetic / physiology*
Substances
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Calcium-Binding Proteins
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Csen protein, mouse
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Enkephalins
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Kv Channel-Interacting Proteins
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Membrane Proteins
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Presenilin-1
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Presenilin-2
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Protein Precursors
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Proto-Oncogene Proteins c-fos
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Receptors, N-Methyl-D-Aspartate
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Receptors, Opioid, kappa
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Repressor Proteins
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preproenkephalin