When the DREAM is gone: from basic science to future prospectives in pain management and beyond

DREAM (downstream regulatory element antagonistic modulator) was identified as a novel calcium-binding protein with pleiotropic functions in vitro that are as varied as that of a transcription factor, a binding partner for presenilins, and a modulator of potassium channels. This review will discuss the findings that have implicated DREAM in its various roles. As a transcriptional repressor, DREAM may control the expression of the endogenous opioid gene prodynorphin amongst others, and itself is exquisitely regulated by second messenger molecules, protein kinases and other transcription factors. Recent genetic evidence has revealed a physiological role for DREAM in pain modulation. The interplay between DREAM and prodynorphin is discussed in light of our current understanding of this Janus-like opioid gene. The potential for the involvement of DREAM in other processes beyond pain modulation is considered at the end of this review.