Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root Ganglia and Spinal Cord Dorsal Horn to Nerve Injury–induced Nociceptive Hypersensitivity

Jun Zhang, Lingli Liang, Xuerong Miao, Shaogen Wu, Jing Cao, Bo Tao, Qingxiang Mao, Kai Mo, Ming Xiong, Brianna Marie Lutz, Alex Bekker, Yuan Xiang Tao

Research output: Contribution to journalArticle

Abstract

BACKGROUND:: Peripheral nerve injury–induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury–induced nociceptive hypersensitivity is unknown. METHODS:: Quantitative real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, or immunohistochemistry were carried out to examine the expression of SUV39H1 mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG μ-opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1 siRNA on fifth lumbar spinal nerve ligation (SNL)–induced DRG MOR down-regulation and nociceptive hypersensitivity were examined. RESULTS:: SUV39H1 was detected in neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1 siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group). CONCLUSIONS:: The findings of this study suggest that SUV39H1 contributes to nerve injury–induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury–induced nociceptive hypersensitivity.

Original languageEnglish (US)
JournalAnesthesiology
DOIs
StateAccepted/In press - Aug 1 2016
Externally publishedYes

Fingerprint

Spinal Ganglia
Hypersensitivity
Spinal Nerves
Hyperalgesia
Ligation
Small Interfering RNA
Microinjections
Spinal Cord Dorsal Horn
Down-Regulation
Messenger RNA
Opioid Receptors
Neuralgia
Peripheral Nerves
Histones
Methylation
Reverse Transcription
Spinal Cord
Proteins
Therapeutics
Western Blotting

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root Ganglia and Spinal Cord Dorsal Horn to Nerve Injury–induced Nociceptive Hypersensitivity. / Zhang, Jun; Liang, Lingli; Miao, Xuerong; Wu, Shaogen; Cao, Jing; Tao, Bo; Mao, Qingxiang; Mo, Kai; Xiong, Ming; Lutz, Brianna Marie; Bekker, Alex; Tao, Yuan Xiang.

In: Anesthesiology, 01.08.2016.

Research output: Contribution to journalArticle

Zhang, Jun ; Liang, Lingli ; Miao, Xuerong ; Wu, Shaogen ; Cao, Jing ; Tao, Bo ; Mao, Qingxiang ; Mo, Kai ; Xiong, Ming ; Lutz, Brianna Marie ; Bekker, Alex ; Tao, Yuan Xiang. / Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root Ganglia and Spinal Cord Dorsal Horn to Nerve Injury–induced Nociceptive Hypersensitivity. In: Anesthesiology. 2016.
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abstract = "BACKGROUND:: Peripheral nerve injury–induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury–induced nociceptive hypersensitivity is unknown. METHODS:: Quantitative real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, or immunohistochemistry were carried out to examine the expression of SUV39H1 mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG μ-opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1 siRNA on fifth lumbar spinal nerve ligation (SNL)–induced DRG MOR down-regulation and nociceptive hypersensitivity were examined. RESULTS:: SUV39H1 was detected in neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1 siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group). CONCLUSIONS:: The findings of this study suggest that SUV39H1 contributes to nerve injury–induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury–induced nociceptive hypersensitivity.",
author = "Jun Zhang and Lingli Liang and Xuerong Miao and Shaogen Wu and Jing Cao and Bo Tao and Qingxiang Mao and Kai Mo and Ming Xiong and Lutz, {Brianna Marie} and Alex Bekker and Tao, {Yuan Xiang}",
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AU - Zhang, Jun

AU - Liang, Lingli

AU - Miao, Xuerong

AU - Wu, Shaogen

AU - Cao, Jing

AU - Tao, Bo

AU - Mao, Qingxiang

AU - Mo, Kai

AU - Xiong, Ming

AU - Lutz, Brianna Marie

AU - Bekker, Alex

AU - Tao, Yuan Xiang

PY - 2016/8/1

Y1 - 2016/8/1

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AB - BACKGROUND:: Peripheral nerve injury–induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury–induced nociceptive hypersensitivity is unknown. METHODS:: Quantitative real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, or immunohistochemistry were carried out to examine the expression of SUV39H1 mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG μ-opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1 siRNA on fifth lumbar spinal nerve ligation (SNL)–induced DRG MOR down-regulation and nociceptive hypersensitivity were examined. RESULTS:: SUV39H1 was detected in neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1 siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group). CONCLUSIONS:: The findings of this study suggest that SUV39H1 contributes to nerve injury–induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury–induced nociceptive hypersensitivity.

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