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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

Authors

  • 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

Journal

Cell

Publication Data

January 11, 2002

Associated Grants

None

Mesh Terms

  • 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