REPORT

New targets II

DREAMing about arthritic pain

H-Y M Cheng^1,2, J M Penninger^1,2

¹ IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
² Departments of Medical Biophysics and Immunology and the University Health, Network, University of Toronto, Toronto, Ontario, Canada

Correspondence to:
Correspondence to:
J Penninger
IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr Gasse 3-5, A-1030 Vienna, Austria; Josef.penninger{at}imba.oeaw.ac.at

The experience of acute pain serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioural responses which protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Despite recent advances in our understanding of pain mechanisms, the satisfactory management of pathological pain eludes current treatment strategies. We have demonstrated in a previous study on dream deficient mice the pivotal role of downstream regulatory element antagonistic modulator (DREAM) in modulating pain sensitivity in a number of behavioural models, including acute and chronic neuropathic pain. DREAM is a novel calcium binding transcriptional repressor for the prodynorphin gene in spinal cord neurones. The marked attenuation in pain behaviour exhibited by dream^–/– mice was shown, by pharmacological and biochemical analyses, to be due to increased activation of the endogenous -opioid system. Importantly, loss of DREAM also attenuated inflammatory pain. Thus, DREAM and the DREAM pathway constitute a novel therapeutic paradigm for the treatment of chronic pain in arthritis.

Abbreviations: AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; CGRP, calcitonin gene related peptide; EAA, excitatory amino acid; DRE, downstream regulatory element; DREAM, downstream regulatory element antagonistic modulator; HPA, hypothalamic–pituitary–adrenal; NMDA, N-methyl-D-aspartate; PGE₂, prostaglandin E₂; RA, rheumatoid arthritis

Keywords: arthritic pain; transcriptional regulation; DREAM; opioid; dynorphin

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