Infection by human varicella-zoster virus confers norepinephrine sensitivity to sensory neurons from rat dorsal root ganglia.
Varicella-zoster virus (VZV) is a widespread human herpes virus causing chicken pox on primary infection and persisting in sensory neurons. Reactivation causes shingles, which are characterized by severe pain and often lead to postherpetic neuralgia. To elucidate the mechanisms of VZV-associated hyperalgesia, we elaborated an in vitro model for the VZV infection of sensory neurons from rat dorsal root ganglia. Between 35 and 50% of the neurons showed strong expression of the immediate-early virus antigens IE62 and IE63 and the late glycoprotein gE. When the intracellular calcium concentration was monitored microfluorometrically for individual cells after infection, the sensitivity to GABA or capsaicin was similar in controls and in VZV-infected neurons. However, the baseline calcium concentration was increased. Neurons became de novo sensitive to adrenergic stimulation after VZV infection. Norepinephrine-responsive neurons were more frequent and calcium responses to norepinephrine were significantly higher after infection with wild-type isolates than with the attenuated vaccine strain OKA. The adrenergic agonists phenylephrine and isoproterenol had similar efficacy. We suggest that the infection with wild-type VZV isolates confers norepinephrine sensitivity to sensory neurons by using alpha(1)- and/or beta(1)-adrenergic receptors providing a model for the pathophysiology of the severe pain associated with the acute reactivation of VZV.
Kress
M
M
Institut für Physiologie und Experimentelle Pathophysiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany. kress@physiologie1.uni-erlangen.de
Fickenscher
H
H
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D006562:Herpes Zoster / Q000473:pathology*; D014645:Herpesvirus 3, Human; D006801:Humans; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism
D011941:Receptors, Adrenergic; D009638:Norepinephrine