DREAM is a critical transcriptional repressor for pain modulation.
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.
Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
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.
PMID: 11792319 [PubMed - indexed for MEDLINE]