DREAM regulates BDNF-dependent spinal sensitization.

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 Ca(2+)- 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.

• Authors: Ivan Rivera-Arconada, Tomaso Benedet, Carolina Roza, Begoña Torres, Jorge Barrio, Agnieszka Krzyzanowska, Carlos Avendaño, Britt Mellström, José A Lopez-Garcia, José R Naranjo
• Journal: Molecular pain (Mol Pain) Vol. 6 Pg. 95 (Dec 18 2010) ISSN: 1744-8069 [Electronic] United States
• PMID: 21167062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Csen protein, mouse
• Kv Channel-Interacting Proteins
• Mutant Proteins
• Repressor Proteins

Topics

• Animals
• Brain-Derived Neurotrophic Factor (antagonists & inhibitors, genetics, physiology)
• Gene Expression Regulation
• Inflammation
• Kv Channel-Interacting Proteins (genetics, physiology)
• Mice
• Mice, Transgenic
• Mutant Proteins
• Nerve Fibers, Unmyelinated (physiology)
• Pain (genetics)
• Rats
• Repressor Proteins (genetics, physiology)
• Spinal Cord (physiology)