Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.

Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nobuhiro Ogawa, Hiromichi Kawai, Tomoya Terashima, Hideto Kojima, Kazuhiro Oka, Lawrence Chan, Hiroshi Maegawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3325c598e6a640f992e24aace7e17915
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3325c598e6a640f992e24aace7e17915
record_format	dspace
spelling	oai:doaj.org-article:3325c598e6a640f992e24aace7e179152021-11-18T08:27:37ZGene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.1932-620310.1371/journal.pone.0092073https://doaj.org/article/3325c598e6a640f992e24aace7e179152014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24642694/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain.Nobuhiro OgawaHiromichi KawaiTomoya TerashimaHideto KojimaKazuhiro OkaLawrence ChanHiroshi MaegawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92073 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nobuhiro Ogawa Hiromichi Kawai Tomoya Terashima Hideto Kojima Kazuhiro Oka Lawrence Chan Hiroshi Maegawa Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
description	Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain.
format	article
author	Nobuhiro Ogawa Hiromichi Kawai Tomoya Terashima Hideto Kojima Kazuhiro Oka Lawrence Chan Hiroshi Maegawa
author_facet	Nobuhiro Ogawa Hiromichi Kawai Tomoya Terashima Hideto Kojima Kazuhiro Oka Lawrence Chan Hiroshi Maegawa
author_sort	Nobuhiro Ogawa
title	Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
title_short	Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
title_full	Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
title_fullStr	Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
title_full_unstemmed	Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
title_sort	gene therapy for neuropathic pain by silencing of tnf-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3325c598e6a640f992e24aace7e17915
work_keys_str_mv	AT nobuhiroogawa genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT hiromichikawai genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT tomoyaterashima genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT hidetokojima genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT kazuhirooka genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT lawrencechan genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice AT hiroshimaegawa genetherapyforneuropathicpainbysilencingoftnfaexpressionwithlentiviralvectorstargetingthedorsalrootganglioninmice
_version_	1718421731836690432

Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.

Ejemplares similares