Paul R Kinchington, PhD Professor, Ophthalmology
Our goal is to understand the underlying molecular basis of the pain associated with post herpetic neuralgia (PHN) associated with “shingles”, or Herpes zoster, and to identify ways to more effectively block it. Zoster and PHN are both caused by the reactivation of varicella zoster virus (VZV), a human herpesvirus, from its neuronal latent state that was established in the hosts sensory ganglia during the primary infection, chickenpox. Zoster ultimately affects some one fifth of the population, and 1/3rd of these will suffer some form of persistent pain and debilitating PHN. Towards these goals, we have working in our hands a new model of PHN in the rat, where injection with human VZV into the footpad induces behavioral changes, including a prolonged allodynia (increased touch sensitivity) and a thermal hyperalgesia (withdrawal to temperature). We are using this model in conjunction with histological and molecular techniques to identify the VZV proteins that are responsible for the induction of the pain responses. By characterizing such VZV proteins and determining how they induce the pain response, we may identify new targets for drugs to ameliorate VZV induced pain. We are also developing recombinant VZV vaccines that lack specific proteins that may be involved in the induction of pain. In this way, we may be able to generate improved vaccines that are unable to induce pain. Our third goal is to use a second herpesvirus, HSV-1, in neuronal gene delivery methods to alter the inhibitory tone of the pain response at the local level as an alternative strategy of treatment, ands to prevent the possible inflammatory causes that may contribute to PHN. This work is a collaborative project involving expertise in molecular manipulation of herpesviruses with behavioral neuroscience and includes the Investigators Dr Jim Goss and Dr Bill Goins.