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Title: Bacterial-neuronal interaction : investigations into the potential mechanisms of dental pain
Author: Kaewpitak, Aunwaya
ISNI:       0000 0004 5922 1465
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Dental inflammatory pain is mainly caused by bacterial infection. Although the culprit bacteria vary from case-to-case, at least one species of black-pigmented, anaerobic bacteria is usually present. Porphyromonas gingivalis is one such species and which is known to possess a number of virulence factors that can contribute to the inflammatory process. However, the mechanisms involved in the pathogenesis of pain during bacterial infection of the dental pulp remain unclear. Therefore, using a trigeminal ganglion (TG) culture system as a model of bacterial infection provides the opportunity to analyse the effects of bacterial components on sensory neurones and the help identify the cellular receptors that could mediate pain. The aim of theses studies was to utilise mouse TG cultures to investigate the direct effects of P. gingivalis cells and two of its well-known virulence factors (lipopolysaccharide and gingipain proteases) in activation of neuronal responses. Our findings provide the first evidence that P. gingivalis, LPS and gingipains can elicit a rapid excitatory response in sensory neurones. These effects appear to be mediated through Toll-like receptors (TLRs), transient receptor potential channels (TRPs), and protease-activated receptors (PARs). These responses were accompanied by an elevated release of the neuropeptide calcitonin-gene related peptide (CGRP) and NF-κB nuclear translocation, both of which are known to regulate a range of pro-inflammatory effects. Here, we also demonstrate for the first time that neuronal supporting cells are also sensitive to P. gingivalis and its components. This provides a further mechanism by which P. gingivalis and other Gram-negative pathogens may manipulate trigeminal sensory neurones and contribute to acute and chronic inflammatory pain. In the light of these investigations, we lend weight to the argument that the neurones are being acted upon directly by the bacteria as well as by local host inflammatory mediators. Moreover, since TRPA1, TLR4, and PAR2 are involved in response to bacterial stimuli, these receptors could be potential targets for the control of dental inflammatory pain.
Supervisor: Douglas, Charles ; Boissonade, Fiona Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available