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Article: Central Endothelin-1 Confers Analgesia by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nuclear Exclusion in Peripheral Neuropathic Pain in Mice

TitleCentral Endothelin-1 Confers Analgesia by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nuclear Exclusion in Peripheral Neuropathic Pain in Mice
Authors
KeywordsPeripheral neuropathic pain
endothelin-1
histone deacetylase 5
glutamate acid decarboxylases
anti-nociception
Issue Date2021
PublisherChurchill Livingstone. The Journal's web site is located at http://www.elsevier.com/locate/jpain
Citation
The Journal of Pain, 2021, v. 22 n. 4, p. 454-471 How to Cite?
AbstractThe rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain.
Persistent Identifierhttp://hdl.handle.net/10722/296322
ISSN
2023 Impact Factor: 4.0
2023 SCImago Journal Rankings: 1.339
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGU, P-
dc.contributor.authorFAN, T-
dc.contributor.authorWong, SSC-
dc.contributor.authorPan, Z-
dc.contributor.authorTAI, WL-
dc.contributor.authorChung, SK-
dc.contributor.authorCheung, CW-
dc.date.accessioned2021-02-22T04:53:40Z-
dc.date.available2021-02-22T04:53:40Z-
dc.date.issued2021-
dc.identifier.citationThe Journal of Pain, 2021, v. 22 n. 4, p. 454-471-
dc.identifier.issn1526-5900-
dc.identifier.urihttp://hdl.handle.net/10722/296322-
dc.description.abstractThe rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain.-
dc.languageeng-
dc.publisherChurchill Livingstone. The Journal's web site is located at http://www.elsevier.com/locate/jpain-
dc.relation.ispartofThe Journal of Pain-
dc.subjectPeripheral neuropathic pain-
dc.subjectendothelin-1-
dc.subjecthistone deacetylase 5-
dc.subjectglutamate acid decarboxylases-
dc.subjectanti-nociception-
dc.titleCentral Endothelin-1 Confers Analgesia by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nuclear Exclusion in Peripheral Neuropathic Pain in Mice-
dc.typeArticle-
dc.identifier.emailWong, SSC: wongstan@hku.hk-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.authorityWong, SSC=rp01789-
dc.identifier.authorityCheung, CW=rp00244-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jpain.2020.12.004-
dc.identifier.pmid33421591-
dc.identifier.scopuseid_2-s2.0-85099348601-
dc.identifier.hkuros321438-
dc.identifier.volume22-
dc.identifier.issue4-
dc.identifier.spage454-
dc.identifier.epage471-
dc.identifier.isiWOS:000717462900008-
dc.publisher.placeUnited States-

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