Neuronal changes induced by Varicella Zoster Virus in a rat model of Post Herpetic Neuralgia
ABSTRACT: Neuronal reactivation of latent varicella zoster virus (VZV) causes debilitating and protracted pain (post herpetic neuralgia: PHN) in a significant fraction of patients. Productive infection of VZV seems to occur only in humans and primates, so VZV-infected human cells (e.g., MEWO cell line) are used to transmit VZV to rodents. A commonly accepted method of assessing nociception is ipsilateral nocifensive (pain avoidance) behavior in rats which have been injected in a footpad. No such behavioral change is associated with the contralateral (uninjected) footpad. Uninfected MEWO cells or VZV-infected MEWO cells were inoculated into the glabrous region of the right rear footpad of male Sprague-Dawley rats. By 9 days post-inoculation, there was a VZV-dependent decrease in the frequency of neurites that extend from the dermis past the stratum basale layer of the footpad epidermis. Between 7 days and 21 days post-inoculation there was a VZV-dependent increase in nocifensive behaviours in the rats. All VZV-dependent effects occurred in the absence of the productive VZV infection. That is, the virus entered rodent cells and expressed immediate early and early genes, but did not express late genes, synthesize viral DNA, or release infectious virions. Animals which had developed VZV-dependent nocifensive behaviours at 10 days were euthanized, and dorsal root ganglia (L4,5) ipsilateral to inoculation were taken for microarray analysis. Dorsal root ganglia from matching control animals were also analyzed. Control (uninfected MEWO cells) or VZV-infected MEWO cells were inoculated into the glabrous region of the right rear footpad of male Sprague-Dawley rats. After development of ipsilateral nocifensive behaviour in the VZV-infected animals, the ipsilateral dorsal root ganglia (L4,5) from infected and control animals were taken for microarray analysis.
ORGANISM(S): Rattus norvegicus
PROVIDER: E-GEOD-64345 | BioStudies |