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DREAM regulates BDNF-dependent spinal sensitization.

Ivan Rivera-Arconada1, Tomaso Benedet, Carolina Roza

  • 1Department of Physiology, Faculty of Medicine, University of Alcala, Madrid, Spain.

Molecular Pain
|December 21, 2010
PubMed
Summary
This summary is machine-generated.

The DREAM protein regulates pain responses. Transgenic mice lacking functional DREAM showed reduced pain gene expression and failed to develop spinal sensitization after inflammation, indicating DREAM

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pain Research

Background:

  • The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) influences pain responses.
  • DREAM controls prodynorphin expression and endogenous pain modulation.
  • Investigating DREAM's role in central pain sensitization mechanisms is crucial.

Purpose of the Study:

  • To investigate the role of DREAM in central pain sensitization.
  • To analyze the impact of a Ca(2+)- and cAMP-insensitive DREAM mutant on pain pathways.

Main Methods:

  • Utilized transgenic mice (L1) overexpressing a mutant DREAM protein in the spinal cord and dorsal root ganglia.
  • Assessed gene expression (prodynorphin, BDNF) in transgenic and wild-type mice.
  • Evaluated spinal reflexes and neuronal responses to inflammation and electrical stimulation in vitro.

Main Results:

  • Transgenic mice exhibited reduced spinal expression of pain-related genes, including prodynorphin and BDNF.
  • These mice displayed basal hyperalgesia but lacked spinal sensitization following peripheral inflammation.
  • Inflammation-induced enhancement of spinal reflexes and BDNF expression were absent in transgenic mice.
  • Exogenous BDNF induced long-term potentiation in transgenic mice, suggesting a blockade of endogenous BDNF signaling.

Conclusions:

  • Endogenous BDNF plays a significant role in spinal sensitization following peripheral inflammation.
  • The failure of spinal sensitization in DREAM transgenic mice is attributed to the blockade of BDNF induction.
  • DREAM is a key regulator of inflammatory pain sensitization through its control over BDNF signaling.