title: DREAM is a critical transcriptional repressor for pain modulation.
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.
authors.affiliation: Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Hai-Ying M
authors.initials: HY
authors.lastname: Cheng
authors.forename: Graham M
authors.initials: GM
authors.lastname: Pitcher
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
authors.forename: Ian Q
authors.initials: IQ
authors.lastname: Whishaw
authors.forename: Kit I
authors.initials: KI
authors.lastname: Tong
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Kockeritz
authors.forename: Teiji
authors.initials: T
authors.lastname: Wada
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Joza
authors.forename: Michael
authors.initials: M
authors.lastname: Crackower
authors.forename: Jason
authors.initials: J
authors.lastname: Goncalves
authors.forename: Ildiko
authors.initials: I
authors.lastname: Sarosi
authors.forename: James R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Oliveira-dos-Santos
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
mesh_terms: 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*
chemical_list: 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