title: 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.affiliation: Department of Physiology, Faculty of Medicine, University of Alcala, Madrid, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rivera-Arconada
authors.forename: Tomaso
authors.initials: T
authors.lastname: Benedet
authors.forename: Carolina
authors.initials: C
authors.lastname: Roza
authors.forename: Begoña
authors.initials: B
authors.lastname: Torres
authors.forename: Jorge
authors.initials: J
authors.lastname: Barrio
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Krzyzanowska
authors.forename: Carlos
authors.initials: C
authors.lastname: Avendaño
authors.forename: Britt
authors.initials: B
authors.lastname: Mellström
authors.forename: José A
authors.initials: JA
authors.lastname: Lopez-Garcia
authors.forename: José R
authors.initials: JR
authors.lastname: Naranjo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D007249:Inflammation; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D010146:Pain / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C496756:Csen protein, mouse; D051605:Kv Channel-Interacting Proteins; D050505:Mutant Proteins; D012097:Repressor Proteins