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Title: Molecular and cellular mechanisms of nociception in equine laminitis : purinergic P2X receptors expression and distribution
Author: Zamboulis, Danae
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2013
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Equine laminitis manifests as a painful condition of the foot and is characterised by disruption of the dermo-epidermal lamellar bond within the equine hoof. Chronic pain in laminitis leads to debilitation and if unchecked euthanasia of the horse and is therefore a significant welfare issue for horses worlwide. P2X receptors are shown to have a pivotal role in pain pathways as well as other tissue functions making them attractive candidates for research in naturally occurring diseases such as equine laminitis. In this study, the presence and distribution of P2X receptors in tissues of the equine digit and its associated vasculature and innervation was investigated. The investigation was extended to tissues from horses suffering from naturally occurring chronic active lamintis in an attempt to identify changes in distribution or expression of the receptors in these tissues. Finally, the functionality of the P2X receptors expressed in equine nervous tissue was investigated. Gene expression (mRNA) for all seven receptors was found in the studied tissues and protein expression for P2X1-3 and 7 receptor subtype proteins in these tissues was confirmed with Western blot analysis. Immunohistochemical analysis of P2X1-3 and 7 receptor subtypes distribution showed differential cellular distribution within normal equine tissue and differential distribution and expression between normal and diseased tissues too. In particular, in a horse with shorter duration of chronic laminitis (1 month), P2X3 receptor subtype immunostaining in DRG neurons presented a marked increase in large neurons which coincided with a decrease in the proportion of these neurons in the DRG. Also, horses suffering from chronic laminitis displayed expression of P2X3 receptor subtype in smooth muscle cells of the palmar digital artery which was absent in normal horses. In chronic laminitic hooves, P2X7 receptor subtype showed particularly strong staining in partially keratinised cells. Finally, intracellular calcium measurements provided evidence for the presence of functional purinergic and P2X receptors in equine spinal cord and DRG cells, respectively. The expression of P2X receptor subtypes in key equine tissues for laminitis and chronic pain in laminitis and their differential expression in laminitic tissues highlights a potential role in chronic laminitis molecular mechanisms. Further research in this area may provide insights into putative targets for disease modulation and pain management in chronic laminitis and other conditions of the horse associated with chronic pain.
Supervisor: Milner, Peter; Senior, J. M.; Clegg, Peter D.; Gallagher, James Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: SF Animal culture