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Paul R Kinchington, Benjamin Warner, William Goins, Mahesh Rao, Crystal Stinson, Phillip Kramer; A rat model of facial Post Herpetic Neuralgia (PHN) induced by Varicella Zoster Virus (VZV). Invest. Ophthalmol. Vis. Sci. 2017;58(8):2990.
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© ARVO (1962-2015); The Authors (2016-present)
Facial zoster and Herpes Zoster Ophthalmicus (HZO) are caused by the reactivation of VZV from neuronal latency, and often result in problematic sequelae that impair vision and well-being. This includes debilitating prolonged pain in the facial/periorbital region (Post Herpetic Neuralgia, or PHN). The strictly limited human host specificity of VZV has made in vivo study of VZV pathogenesis, latency and reactivation rather difficult. However, live VZV innoculated into the footpads of rats induce chronic behaviors of pain. The goal of this work was to determine if facial, ocular and periorbital VZV PHN models could be developed.
Sprague Dawley Rats (n=4 to 6) were innoculated at the facial or periorbital region with live cell-associated VZV (1x10^5). Control rats recieved received uninfected cell equivalents or UV-irradiated VZV. Affective pain was asssessed weekly using the Fuchs Place-Escape-Avoidance-Paradigm (PEAP) involving periodic facial stimulation with 38g or 60g filaments in split light/dark chambers. Pain was assessed by avoidance of dark sides of testing chambers over 30 min periods. Both sexes were evaluated.
PEAP testing relies on rat preference of the dark side of split dark/light testing chambers. Live cell-associated VZV inoculation, but not inoculation of UV-irradiated VZV or uninfected cells, induced signficant avoidance of the preferred dark side when facial sites of inoculation were stimulated. Behaviors suggesting pain initated rapidly by week 1, required VZV infectivity and lasted for 6-9 weeks p.i. A more prolonged and stronger pain response developed in female over male rats.
This new VZV facial chronic pain model expands upon the footpad VZV chronic pain model, and permits modeling of facial and trigeminal pain seen in VZV HZO patients and viral infection of trigeminal ganglia. While pain develops following a VZV primary infection (unlike human PHN, which follows VZV reactivation and zoster), it may open avenues to test novel anti-VZV and PHN therapeutics and permit study of VZV -ganglia interactions leading to pain. The data indicate viral gene expression is required for pain development, even though our work indicates rats are not fully permissive for VZV replication. Sex based differences mirror an increased female to male propensity for PHN in humans.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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