HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Franziska Denk, Wenlong Huang, Ben Sidders, Angela Bithell, Megan Crow, John Grist, Simone Sharma, Daniel Ziemek, Andrew S C Rice, Noel J. Buckley, Stephen B. McMahon

Research output: Contribution to journalArticle

74 Citations (Scopus)
4 Downloads (Pure)

Abstract

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.
Original languageEnglish
Pages (from-to)1668-1679
Number of pages12
JournalPain
Volume154
Issue number9
Early online date18 May 2013
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Histone Deacetylase Inhibitors
Neuralgia
Acetylation
Histones
Hypersensitivity
Spinal Cord
Genetic Epigenesis
Stavudine
Spinal Ganglia
Peripheral Nervous System Diseases
Microarray Analysis
Chronic Pain
Pharmaceutical Preparations
Analgesics
Central Nervous System
Hot Temperature
RNA
Wounds and Injuries
Therapeutics

Keywords

  • histone deacetylase
  • histone deacetylase inhibitors
  • neuropathic pain

Cite this

Denk, F., Huang, W., Sidders, B., Bithell, A., Crow, M., Grist, J., ... McMahon, S. B. (2013). HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. Pain, 154(9), 1668-1679. https://doi.org/10.1016/j.pain.2013.05.021

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. / Denk, Franziska; Huang, Wenlong; Sidders, Ben; Bithell, Angela; Crow, Megan; Grist, John; Sharma, Simone; Ziemek, Daniel; Rice, Andrew S C; Buckley, Noel J. ; McMahon, Stephen B.

In: Pain, Vol. 154, No. 9, 09.2013, p. 1668-1679.

Research output: Contribution to journalArticle

Denk, F, Huang, W, Sidders, B, Bithell, A, Crow, M, Grist, J, Sharma, S, Ziemek, D, Rice, ASC, Buckley, NJ & McMahon, SB 2013, 'HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain', Pain, vol. 154, no. 9, pp. 1668-1679. https://doi.org/10.1016/j.pain.2013.05.021
Denk, Franziska ; Huang, Wenlong ; Sidders, Ben ; Bithell, Angela ; Crow, Megan ; Grist, John ; Sharma, Simone ; Ziemek, Daniel ; Rice, Andrew S C ; Buckley, Noel J. ; McMahon, Stephen B. / HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. In: Pain. 2013 ; Vol. 154, No. 9. pp. 1668-1679.
@article{c7bfc54b970d44828ff6eef5ada66c19,
title = "HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain",
abstract = "Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40{\%} to 50{\%} as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.",
keywords = "histone deacetylase, histone deacetylase inhibitors, neuropathic pain",
author = "Franziska Denk and Wenlong Huang and Ben Sidders and Angela Bithell and Megan Crow and John Grist and Simone Sharma and Daniel Ziemek and Rice, {Andrew S C} and Buckley, {Noel J.} and McMahon, {Stephen B.}",
year = "2013",
month = "9",
doi = "10.1016/j.pain.2013.05.021",
language = "English",
volume = "154",
pages = "1668--1679",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "9",

}

TY - JOUR

T1 - HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

AU - Denk, Franziska

AU - Huang, Wenlong

AU - Sidders, Ben

AU - Bithell, Angela

AU - Crow, Megan

AU - Grist, John

AU - Sharma, Simone

AU - Ziemek, Daniel

AU - Rice, Andrew S C

AU - Buckley, Noel J.

AU - McMahon, Stephen B.

PY - 2013/9

Y1 - 2013/9

N2 - Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

AB - Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

KW - histone deacetylase

KW - histone deacetylase inhibitors

KW - neuropathic pain

UR - http://www.scopus.com/inward/record.url?scp=84881661407&partnerID=8YFLogxK

U2 - 10.1016/j.pain.2013.05.021

DO - 10.1016/j.pain.2013.05.021

M3 - Article

C2 - 23693161

AN - SCOPUS:84881661407

VL - 154

SP - 1668

EP - 1679

JO - Pain

JF - Pain

SN - 0304-3959

IS - 9

ER -