DREAM is a critical transcriptional repressor for pain modulation

Cell. 2002 Jan 11;108(1):31-43. doi: 10.1016/s0092-8674(01)00629-8.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Behavior, Animal / physiology
  • Calcium-Binding Proteins*
  • Cells, Cultured
  • Consensus Sequence
  • Down-Regulation / physiology
  • Enkephalins / genetics
  • Enkephalins / metabolism
  • Heart / physiology
  • Hyperalgesia / physiopathology
  • Inflammation / physiopathology
  • Kv Channel-Interacting Proteins
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuralgia / immunology
  • Neuralgia / physiopathology*
  • Neurons / cytology
  • Neurons / physiology
  • Physical Stimulation
  • Presenilin-1
  • Presenilin-2
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Spinal Cord / cytology
  • Stimulation, Chemical
  • Transcription, Genetic / physiology*

Substances

  • Calcium-Binding Proteins
  • Csen protein, mouse
  • Enkephalins
  • Kv Channel-Interacting Proteins
  • Membrane Proteins
  • Presenilin-1
  • Presenilin-2
  • Protein Precursors
  • Proto-Oncogene Proteins c-fos
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid, kappa
  • Repressor Proteins
  • preproenkephalin