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Notice Board Topics
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| Rodent model of Zoster-associated pain |
Background
Varicella-Zoster virus (VZV) is a neurotropic virus, which causes varicella (chickenpox) as the primary infection. Following the acute illness, the virus establishes latency within sensory ganglia in the peripheral nervous system (PNS). VZV may be reactivated years later and present as herpes zoster (shingles). Although mechanisms of reactivation from ganglia have not been fully identified, dysfunction of cellular immunity is thought to be involved. Shingles may be followed by the development of post-herpetic neuralgia (PHN), a common neuropathic pain syndrome that persists even when the virus becomes latent within the sensory ganglia of the affected dermatomes and long after the disappearance of skin lesions.
Clinical relevance
PHN is characterised by the development of persistent hyperalgesia and allodynia, accompanied by spontaneous pain typically of a burning or aching nature. It responds poorly to classical analgesics and as such is associated with significant morbidity. The treatments with the strongest evidence base are opioids, tricyclic antidepressants and gabapentin but these are only effective in 30-50% of patients and are
associated with unacceptable adverse effect profiles. This presents a need for the investigation of the mechanisms involved in the establishment of post-herpetic neuralgia and in the development of effective drugs for its treatment. An animal model of zoster-associated pain would increase our understanding of the pathophysiology of this condition and provide a pre-clinical screen for novel analgesic drugs.
Proposed Experiments
A well established rodent model of latent VZV infection will be refined [Fleetwood-Walker et al., 1999] to investigate whether rats infected with VZV display behavioural and electrophysiological features, which reflect the clinical picture of human PHN. These behavioural tests will initially include simple reflex withdrawal to mechanical, thermal and cold stimuli. More complex measures of integrated pain behaviour and spinal electrophysiological observations will then be examined. The pharmacological profile of the rodent model to analgesics known to have a degree of efficacy in human neuropathic pain conditions will also be examined. Finally, the association of viral latency with DRG gene correlates of neuropathic pain will be investigated using the Consortium?s microarray facility.
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