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Conference Paper: Central Endothelial-1 Produces Analgesic Function by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nucleocytoplasmic Shuttling Under Neuropathic Pain

TitleCentral Endothelial-1 Produces Analgesic Function by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nucleocytoplasmic Shuttling Under Neuropathic Pain
Authors
Issue Date2018
PublisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1533-2500
Citation
9th World Congress of the World Institute of Pain (WIP), Dublin, Ireland, 9-12 May 2018. In Pain Practice, 2018, v. 18 n. S1, p. 37, abstract no.WIP18-0309 How to Cite?
AbstractObjectives: Neuropathic pain has a considerable impact onpatients’ quality of life, which the mechanism is still elusive.Previously, we reported that central administration of endothe-lial- 1(ET-1) attenuated neuropathic pain, while the rationalesare still unclear. it was reported that ET-1, via kinase activationand HDAC5 phosphorylation, promotes nucleocytoplasmicshuttling of HDAC5 in myocytes, which lead to the activationof HDAC5-dependent cascades. In this study, we aimed toinvestigate whether central ET-1 produces anti-nociceptionrole by triggering HDAC5 nucleocytoplasmic shuttling underneuropathic pain. Methods: ET-1 astrocytic overexpression (GET-1) transgenicmice and C57BL/6N mice were subjected to partial sciaticnerve ligation (pSNL). ET-1 peptide, agonist and antagonist ofEndothelial A receptor (ETAR) and ERK, adeno-associatedviruses of wild type and mutant HDAC5 (AAV-HDAC5-WTand AAV-HDAC5-Mut) and behavioral tests, were employedto determine the role of HDAC5 shuttling in ET-1-induced painrelief. Biochemical analysis were used to explore the ET-1/ETAR-HDAC5 dependent pathway in vitro and in vivo.Results: GET-1 mice transfected by AAV-HDAC5-WTinduced the shuttling of phosphorylated-HDAC5 (p-HDAC5ser498) in cytoplasm of spinal dorsal neurons and increasedspinal dorsal GAD 65, which was reversed by ETAR antagonistand ERK inhibitor. These results were confirmed by AAV-HDAC5-Mut virus infected GET-1 mice which showed moremechanical allodynia and thermal hypersensitivity than AAV-HDAC5-WT GET-1 mice. P-HDAC5 was accumulated inspinal neuronal nucleus and GAD 65 decreased in GET-1 micewith AAV-HDAC5-Mut. Conclusions: In this study, we demonstrated that centraladministration of ET-1 increases GAD65 expression viainducing HDAC5 nucleocytoplasmic shuttling to alleviateneuropathic pain processing.
Persistent Identifierhttp://hdl.handle.net/10722/285370
ISSN
2019 Impact Factor: 2.258
2015 SCImago Journal Rankings: 0.659

 

DC FieldValueLanguage
dc.contributor.authorGu, P-
dc.contributor.authorFan, T-
dc.contributor.authorPan, Z-
dc.contributor.authorCheung, CW-
dc.date.accessioned2020-08-18T03:52:50Z-
dc.date.available2020-08-18T03:52:50Z-
dc.date.issued2018-
dc.identifier.citation9th World Congress of the World Institute of Pain (WIP), Dublin, Ireland, 9-12 May 2018. In Pain Practice, 2018, v. 18 n. S1, p. 37, abstract no.WIP18-0309-
dc.identifier.issn1530-7085-
dc.identifier.urihttp://hdl.handle.net/10722/285370-
dc.description.abstractObjectives: Neuropathic pain has a considerable impact onpatients’ quality of life, which the mechanism is still elusive.Previously, we reported that central administration of endothe-lial- 1(ET-1) attenuated neuropathic pain, while the rationalesare still unclear. it was reported that ET-1, via kinase activationand HDAC5 phosphorylation, promotes nucleocytoplasmicshuttling of HDAC5 in myocytes, which lead to the activationof HDAC5-dependent cascades. In this study, we aimed toinvestigate whether central ET-1 produces anti-nociceptionrole by triggering HDAC5 nucleocytoplasmic shuttling underneuropathic pain. Methods: ET-1 astrocytic overexpression (GET-1) transgenicmice and C57BL/6N mice were subjected to partial sciaticnerve ligation (pSNL). ET-1 peptide, agonist and antagonist ofEndothelial A receptor (ETAR) and ERK, adeno-associatedviruses of wild type and mutant HDAC5 (AAV-HDAC5-WTand AAV-HDAC5-Mut) and behavioral tests, were employedto determine the role of HDAC5 shuttling in ET-1-induced painrelief. Biochemical analysis were used to explore the ET-1/ETAR-HDAC5 dependent pathway in vitro and in vivo.Results: GET-1 mice transfected by AAV-HDAC5-WTinduced the shuttling of phosphorylated-HDAC5 (p-HDAC5ser498) in cytoplasm of spinal dorsal neurons and increasedspinal dorsal GAD 65, which was reversed by ETAR antagonistand ERK inhibitor. These results were confirmed by AAV-HDAC5-Mut virus infected GET-1 mice which showed moremechanical allodynia and thermal hypersensitivity than AAV-HDAC5-WT GET-1 mice. P-HDAC5 was accumulated inspinal neuronal nucleus and GAD 65 decreased in GET-1 micewith AAV-HDAC5-Mut. Conclusions: In this study, we demonstrated that centraladministration of ET-1 increases GAD65 expression viainducing HDAC5 nucleocytoplasmic shuttling to alleviateneuropathic pain processing.-
dc.languageeng-
dc.publisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1533-2500-
dc.relation.ispartofPain Practice-
dc.relation.ispartof9th World Congress of the World Institute of Pain (WIP)-
dc.titleCentral Endothelial-1 Produces Analgesic Function by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nucleocytoplasmic Shuttling Under Neuropathic Pain-
dc.typeConference_Paper-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.authorityCheung, CW=rp00244-
dc.identifier.hkuros312866-
dc.identifier.volume18-
dc.identifier.issueS1-
dc.identifier.spage37-
dc.identifier.epage37-
dc.publisher.placeUnited States-
dc.identifier.partofdoi10.1111/papr.12693-

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