Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia

Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from th...

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Autores principales: Rongzhen Li, Mingxi Ou, Shaomin Yang, Jiabin Huang, Jiamin Chen, Donglin Xiong, Lizu Xiao, Songbin Wu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/b7ed508f5f984f7aafb5c12e293f6f5f
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spelling oai:doaj.org-article:b7ed508f5f984f7aafb5c12e293f6f5f2021-12-01T18:46:19ZChange in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia1664-229510.3389/fneur.2021.741054https://doaj.org/article/b7ed508f5f984f7aafb5c12e293f6f5f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.741054/fullhttps://doaj.org/toc/1664-2295Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.Rongzhen LiMingxi OuShaomin YangJiabin HuangJiamin ChenDonglin XiongLizu XiaoSongbin WuFrontiers Media S.A.articleHerpetic neuralgiaT-type calcium channelCav3.2VZVdorsal root ganglion (DRG)spinal dorsal horn (SDH)Neurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Herpetic neuralgia
T-type calcium channel
Cav3.2
VZV
dorsal root ganglion (DRG)
spinal dorsal horn (SDH)
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Herpetic neuralgia
T-type calcium channel
Cav3.2
VZV
dorsal root ganglion (DRG)
spinal dorsal horn (SDH)
Neurology. Diseases of the nervous system
RC346-429
Rongzhen Li
Mingxi Ou
Shaomin Yang
Jiabin Huang
Jiamin Chen
Donglin Xiong
Lizu Xiao
Songbin Wu
Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
description Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.
format article
author Rongzhen Li
Mingxi Ou
Shaomin Yang
Jiabin Huang
Jiamin Chen
Donglin Xiong
Lizu Xiao
Songbin Wu
author_facet Rongzhen Li
Mingxi Ou
Shaomin Yang
Jiabin Huang
Jiamin Chen
Donglin Xiong
Lizu Xiao
Songbin Wu
author_sort Rongzhen Li
title Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
title_short Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
title_full Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
title_fullStr Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
title_full_unstemmed Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
title_sort change in cav3.2 t-type calcium channel induced by varicella-zoster virus participates in the maintenance of herpetic neuralgia
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/b7ed508f5f984f7aafb5c12e293f6f5f
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