Transcriptional repressor DREAM regulates trigeminal noxious perception

J Neurochem. 2017 May;141(4):544-552. doi: 10.1111/jnc.13584. Epub 2017 Feb 21.

Abstract

Expression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons, high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing a dominant active mutant of DREAM in trigeminal neurons show increased responses following orofacial sensory stimulation, which correlates with a decreased expression of prodynorphin and brain-derived neurotrophic factor in trigeminal ganglia. Genome-wide analysis of trigeminal neurons in daDREAM transgenic mice identified cathepsin L and the monoglyceride lipase as two new DREAM transcriptional targets related to pain. Our results suggest a role for DREAM in the regulation of trigeminal nociception. This article is part of the special article series "Pain".

Keywords: calcium; cathepsins; monoglyceride lipases; orofacial pain; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Cathepsin L / metabolism
  • Enkephalins / biosynthesis
  • Facial Pain / physiopathology
  • Hyperalgesia / physiopathology
  • Kv Channel-Interacting Proteins / genetics*
  • Kv Channel-Interacting Proteins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Monoacylglycerol Lipases / metabolism
  • Nociception / physiology*
  • Physical Stimulation
  • Protein Precursors / biosynthesis
  • Repressor Proteins / genetics*
  • Repressor Proteins / physiology*
  • Transcriptome
  • Trigeminal Nerve / physiology*

Substances

  • Brain-Derived Neurotrophic Factor
  • Csen protein, mouse
  • Enkephalins
  • Kv Channel-Interacting Proteins
  • Protein Precursors
  • Repressor Proteins
  • preproenkephalin
  • Monoacylglycerol Lipases
  • Cathepsin L

Associated data

  • GENBANK/GSE69619