Abstract
BackgroundMost people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or “shingles”. Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference.MethodsTo develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program.ResultsSimilar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain.ConclusionsThese results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.
Highlights
Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox
Virus infected cells incubated at 35 °C for 48–72 h post infection were harvested by trypsin digestion, and optimal VZV cell viability was maintained by slow freezing aliquots in Minimal Essential Media (MEM) containing 20% fetal bovine serum (FBS) and 10% dimethyl sulfoxide
VZV accesses the trigeminal ganglia after whisker pad inoculation In the virus injected group NeuN positive cells co-localize with IE62 within the trigeminal ganglia (Fig. 1a and b)
Summary
Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). No model has been developed to study orofacial pain related to varicella zoster. The incidence of zoster associated pain and PHN is known to be higher in women, reasons for this sex difference remain unclear. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference. Varicella zoster virus (VZV) is a human herpesvirus that infects a majority of the unvaccinated population worldwide. Better prevention and therapy for both zoster and PHN are an unmet need
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