The DREAM of Pain Relief

Chronic pain has manifested itself as an independent disease. Different molecules acting in nociceptive pathways in the periphery and the nervous system are currently under investigation. Recently the multifunctional protein DREAM (D ownstream Regulatory Element Antagonist Modulator)/calsenilin/KChIP3 has been implicated to play a role in the mechanisms of pain modulation and the hypothesis "No DREAM - No pain" was raised. In addition to the binding to DRE (Downstream Regulatory Element) sequences, DREAM/calsenilin/KChIP3 was shown to interact with presenilin, a protein thought to be a key molecule in Alzheimer's disease, and Kv4alpha-subunits assembling potassium channels. DREAM/calsenilin/KChIP3 has been described as a Ca2+-dependent transcriptional repressor, which is targeted to the regulatory DNA sequence of the prodynorphin gene. By actively suppressing gene expression of the endogenous opioid receptor ligand dynorphin, DREAM/calsenilin/KChIP3 is modulating the kappa opioid receptor system, which mediates analgesia. DREAM knockout mice showed elevated levels of dynorphin and consequently displayed attenuated chemical induced and inflammatory pain. The data derived from the DREAM knock-out model led to the identification of a novel target in chronic pain management. In this review we focus on DREAM/calsenilin/KChIP3 and its role in pain relief.