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Open Access Research

DREAM regulates BDNF-dependent spinal sensitization

Ivan Rivera-Arconada1, Tomaso Benedet23, Carolina Roza1, Begoña Torres23, Jorge Barrio2, Agnieszka Krzyzanowska4, Carlos Avendaño4, Britt Mellström23, José A Lopez-Garcia1* and José R Naranjo23*

Author Affiliations

1 Department of Physiology, Faculty of Medicine, University of Alcala, 28871 Madrid, Spain

2 Department of Molecular and Cellular Biology, National Centre for Biotechnology, C.S.I.C., Darwin 3, 28049 Madrid, Spain

3 CNB-CIBERNED, 28049 Madrid, Spain

4 Department of Anatomy, Histology and Neurosciences, Faculty of Medicine, Arzobispo Morcillo s/n, University Autónoma de Madrid, 28029 Madrid, Spain

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Molecular Pain 2010, 6:95  doi:10.1186/1744-8069-6-95

Published: 18 December 2010

Abstract

Background

The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) controls the expression of prodynorphin and has been involved in the modulation of endogenous responses to pain. To investigate the role of DREAM in central mechanisms of pain sensitization, we used a line of transgenic mice (L1) overexpressing a Ca2+- and cAMP-insensitive DREAM mutant in spinal cord and dorsal root ganglia.

Results

L1 DREAM transgenic mice showed reduced expression in the spinal cord of several genes related to pain, including prodynorphin and BDNF (brain-derived neurotrophic factor) and a state of basal hyperalgesia without change in A-type currents. Peripheral inflammation produced enhancement of spinal reflexes and increased expression of BDNF in wild type but not in DREAM transgenic mice. The enhancement of the spinal reflexes was reproduced in vitro by persistent electrical stimulation of C-fibers in wild type but not in transgenic mice. Exposure to exogenous BDNF produced a long-term enhancement of dorsal root-ventral root responses in transgenic mice.

Conclusions

Our results indicate that endogenous BDNF is involved in spinal sensitization following inflammation and that blockade of BDNF induction in DREAM transgenic mice underlies the failure to develop spinal sensitization.