title: Varicella-zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line.
abstract: Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells.
authors: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. Peter.Kennedy@glasgow.ac.uk
authors: Peter G E
authors: PG
authors: Kennedy
authors: Paul
authors: P
authors: Montague
authors: Fiona
authors: F
authors: Scott
authors: Esther
authors: E
authors: Grinfeld
authors: G H
authors: GH
authors: Ashrafi
authors: Judith
authors: J
authors: Breuer
authors: Edward G
authors: EG
authors: Rowan
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006562:Herpes Zoster / Q000150:complications / Q000235:genetics / Q000821:virology; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D051474:Neuralgia, Postherpetic / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D013779:Tetrodotoxin; D000212:Acyclovir
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