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.
Cheng
Hai-Ying M
HY
Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
Pitcher
Graham M
GM
Laviolette
Steven R
SR
Whishaw
Ian Q
IQ
Tong
Kit I
KI
Kockeritz
Lisa K
LK
Wada
Teiji
T
Joza
Nicholas A
NA
Crackower
Michael
M
Goncalves
Jason
J
Sarosi
Ildiko
I
Woodgett
James R
JR
Oliveira-dos-Santos
Antonio J
AJ
Ikura
Mitsuhiko
M
van der Kooy
Derek
D
Salter
Michael W
MW
Penninger
Josef M
JM
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D016384:Consensus Sequence; D015536:Down-Regulation / Q000502:physiology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006930:Hyperalgesia / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000276:immunology / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010812:Physical Stimulation; D053764:Presenilin-1; D053766:Presenilin-2; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology; D013268:Stimulation, Chemical; D014158:Transcription, Genetic / Q000502:physiology*
D002135:Calcium-Binding Proteins; C496756:Csen protein, mouse; D004745:Enkephalins; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D012097:Repressor Proteins; C033660:preproenkephalin