Targeting chronic pain with epigenetic drugs: Focus on mGlu2 receptors

Santina Chiechio, Magda Zammataro, Robert W. Gereau IV, Agata Copani, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

Histone deacetylase (HDAC) enzymes regulate gene expression by affecting chromatin structure and/or the activity of transcription factors. We have recently demonstrated that histone deacetylase inhibitors (HDACIs) behave as epigenetic agents capable of inducing analgesia by up-regulating metabotropic glutamate type 2 (mGlu2) receptors. Specifically, the regulation of mGlu2 receptor expression appears to involve the acetylation of the NF-κB transcription factor. mGlu2 and mGlu3 receptors belong to class II metabotropic glutamate receptors. These receptors are coupled to Gi/o proteins and play an important role in mediating antinociception in a variety of inflammatory and chronic pain models. We have shown that the HDACI-mediated mGlu2 receptor up-regulation occurs in the dorsal horn of the spinal cord and in the dorsal root ganglia, supporting a predominant role for mGlu2 receptors as mediators of analgesia in experimental animal models of chronic pain. We suggest that drugs that increase the expression of mGlu2 receptors, such as HDACIs or acetylating drugs (e.g. L-acetylcarnitine), may be effective in patients with chronic pain that are refractory to conventional analgesics.

Original languageEnglish
Pages (from-to)194-199
Number of pages6
JournalMolecular and Cellular Pharmacology
Volume1
Issue number4
DOIs
Publication statusPublished - 2009

Keywords

  • Chronic pain
  • Epigenetic drugs
  • Histone deacetylase
  • mGlu2 receptors

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Biology

Fingerprint Dive into the research topics of 'Targeting chronic pain with epigenetic drugs: Focus on mGlu2 receptors'. Together they form a unique fingerprint.

  • Cite this