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Title: Zoster-associated pain in rodents
Author: Hasnie, Fauzia Shams
ISNI:       0000 0004 2743 4845
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2007
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Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. However, progress in elucidating the pathophysiology of zoster-associated pain has been hindered by the lack of an appropriate animal model. This thesis refines a recently described rat model of zoster-associated hypersensitivity and investigates behavioural, pharmacological, and gene correlates of neuropathic pain. The influence of viral strain and inoculum concentration on neuropathic pain behaviour in rats was initially investigated. Reflex withdrawal responses were assessed to static punctuate and dynamic mechanical, noxious thermal and cooling stimuli. The model was further validated by examining the pharmacological profile to analgesics known to have a degree of efficacy in human neuropathic pain conditions (e.g. tricyclic antidepressants, opioids and gabapentin) as well as novel analgesic compounds (e.g. cannabinoids) and anti-virals (useful in determining the nature of the model). Behavioural paradigms were then taken beyond stimulus-evoked reflex limb withdrawal paradigms conventionally employed in pain models, to encompass more complex outcome measures of integrated pain behaviour reflecting neuropathic pain co-morbidities (e.g. anxiety-like behaviour in the open field paradigm). Pharmacological sensitivity testing in the open field paradigm was performed in parallel with two further models of traumatic peripheral neuropathy. Finally, a microarray approach was used to globally investigate changes in gene expression in dorsal root ganglia associated with a) Varicella Zoster virus infection and b) spinal nerve transection. In this way, common gene expression changes between models were examined. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and related co-morbidity behaviour and ultimately provide us with greater clinical validity and predictability.
Supervisor: Rice, A. S. C. ; Dickenson, A. H. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available