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

Fingerprint

Epigenomics
Chronic Pain
Histone Deacetylase Inhibitors
Pharmaceutical Preparations
Analgesia
Transcription Factors
Acetylcarnitine
Metabotropic Glutamate Receptors
Histone Deacetylases
Spinal Ganglia
Acetylation
Chromatin
Analgesics
Glutamic Acid
Up-Regulation
Animal Models
metabotropic glutamate receptor 2
Gene Expression
Enzymes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Biology

Cite this

Targeting chronic pain with epigenetic drugs : Focus on mGlu2 receptors. / Chiechio, Santina; Zammataro, Magda; Gereau IV, Robert W.; Copani, Agata; Nicoletti, Ferdinando.

In: Molecular and Cellular Pharmacology, Vol. 1, No. 4, 2009, p. 194-199.

Research output: Contribution to journalArticle

Chiechio, Santina ; Zammataro, Magda ; Gereau IV, Robert W. ; Copani, Agata ; Nicoletti, Ferdinando. / Targeting chronic pain with epigenetic drugs : Focus on mGlu2 receptors. In: Molecular and Cellular Pharmacology. 2009 ; Vol. 1, No. 4. pp. 194-199.
@article{c33af32313f84a168b8ffb39f8705b7b,
title = "Targeting chronic pain with epigenetic drugs: Focus on mGlu2 receptors",
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.",
keywords = "Chronic pain, Epigenetic drugs, Histone deacetylase, mGlu2 receptors",
author = "Santina Chiechio and Magda Zammataro and {Gereau IV}, {Robert W.} and Agata Copani and Ferdinando Nicoletti",
year = "2009",
doi = "10.4255/mcpharmacol.09.23",
language = "English",
volume = "1",
pages = "194--199",
journal = "Molecular and Cellular Pharmacology",
issn = "1938-1247",
publisher = "Lumitext Publishing",
number = "4",

}

TY - JOUR

T1 - Targeting chronic pain with epigenetic drugs

T2 - Focus on mGlu2 receptors

AU - Chiechio, Santina

AU - Zammataro, Magda

AU - Gereau IV, Robert W.

AU - Copani, Agata

AU - Nicoletti, Ferdinando

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Chronic pain

KW - Epigenetic drugs

KW - Histone deacetylase

KW - mGlu2 receptors

UR - http://www.scopus.com/inward/record.url?scp=77953376316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953376316&partnerID=8YFLogxK

U2 - 10.4255/mcpharmacol.09.23

DO - 10.4255/mcpharmacol.09.23

M3 - Article

AN - SCOPUS:77953376316

VL - 1

SP - 194

EP - 199

JO - Molecular and Cellular Pharmacology

JF - Molecular and Cellular Pharmacology

SN - 1938-1247

IS - 4

ER -