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Title: Characterisation of a rat model of post herpetic neuralgia
Author: Kok, W. L.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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An in vivo model of latent VZV was developed in the adult rat by subcutaneous injection of VZV infected cells into the left footpad. Foot reflex withdrawal responses were recorded for longer than 60 days post infection similar to changes seen in PHN patients. The aim of this study was to further characterise this model so that it could provide a useful and unique opportunity to study the host-virus interaction involved in the pathogenesis of PHN. Nested PCR was able to detect viral DNA in the different lumbar DRG. Viral DNA was present in the infected DRG as early as 24 h post infection and viremia was ruled out as no viral DNA could be detected in the blood of these animals at 24 h, 48 h and 72 h or in blood obtained at later time points. This suggested that the spread of the virus is mainly through axonal pathway. Viral DNA could not be detected in other tissues like spleen, spinal cord and brain suggested that the latent virus was limited to the peripheral nervous system. A global approach was taken to look at the transcriptional activity in the latently infected neurones by carrying out a microarray experiment. The Rat Expression Set 230A GeneChip used comprise of 15,866 known rat genes. Of the 15866 probe sets represented on the RAE 230A, 5295 probe sets were not detected (33%). 9556 genes detected on both samples, of which 332 with altered expression and 57 of them has an increase in expression. Of the 57 increased in expression, there were 32 which met the cutoff value of 50 and only 5 had a fold change of greater than 2. Among them, prostaglandin D2 synthase was found to be upregulated three fold and validation of this gene by real time PCR shows an upregulation of 2.7 fold. This study is in effect a pilot study giving a general overview of the changes within the DRG and thus provide a source of further characterisation of this model to the pathogenesis of the VZV induced allodynia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available