Author/Authors :
Hai-Ying M. Cheng، نويسنده , , Graham M. Pitcher، نويسنده , , Steven R. Laviolette، نويسنده , , Ian Q. Whishaw، نويسنده , , Kit I. Tong، نويسنده , , Lisa K. Kockeritz، نويسنده , , Teiji Wada، نويسنده , , Nicholas A. Joza، نويسنده , , Michael Crackower، نويسنده , , Jason Goncalves، نويسنده , , Ildiko Sarosi، نويسنده , , James R. Woodgett، نويسنده , , Antonio J. Oliveira-dos-Santos، نويسنده , , Mitsuhiko Ikura، نويسنده , , Derek van der Kooy، نويسنده , , Michael W. Salter، نويسنده , , Josef M. Penninger، نويسنده ,
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 (κ)-opiate receptors. Thus, DREAM appears to be a critical transcriptional repressor in pain processing.
