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dc.contributor.supervisorThompson, Stephen W N
dc.contributor.authorTriner, Joceline Clare
dc.contributor.otherFaculty of Science and Engineeringen_US
dc.date.accessioned2013-07-26T15:11:04Z
dc.date.available2013-07-26T15:11:04Z
dc.date.issued2013
dc.date.issued2013
dc.identifier385009en_US
dc.identifier.urihttp://hdl.handle.net/10026.1/1585
dc.description.abstract

The trigeminal ganglion (TG) is a complex sensory structure and multiple lines of evidence suggest that significant differences exist in anatomical, neurochemical and physiological properties between it and its equivalent structure in the somatosensory system, the dorsal root ganglion (DRG). This is likely to be a reflection, first on the unique areas of tissue innervation of the TG and second, on the unusual responses to injury which give rise to distinct pain symptoms such as toothache, migraine and temporomandibular joint disorders. In an attempt to address this disparity in knowledge, we have carried out an in-depth in vivo study investigating neurochemical populations and cell size distributions of sensory neurons within the rat TG. We have performed a detailed analysis of expression patterns for receptor components of important inflammatory mediators, NGF (TrkA), TNFα (p55) and IL-6 (gp130), along with the thermo-transducers TRPV1 and TRPM8. For each analysis we have compared our findings with those of the rat DRG.

We have shown a significantly larger population of NF200+ neurons within the TG (51%) compared to the DRG (40%), and most interestingly, the majority of NF200+ neurons in the TG were within the small to medium cell size range, conferring a nociceptive phenotype. We have for the first time, determined expression of p55 and gp130 protein levels within neurochemically defined subpopulations of the TG. We show that a large proportion (33%) of TG neurons, in particular 27% of NF200+ neurons co-express p55, and thereby have the potential to respond directly to TNFα. Furthermore, we have observed gp130 protein expression to be ubiquitous within the TG, suggesting all neurons, including non-nociceptors, could respond to IL-6.

In addition, we have utilised biochemical and electrophysiological techniques in vitro to measure the functional outcome of exposure of TG neurons to IL-6. We have demonstrated that IL-6 activates the JAK/STAT signalling pathway, preferentially within NF200+ neurons. Furthermore, we have shown that IL-6 sensitises the response of TG neurons to the TRPV1 agonist capsaicin, altering the gating properties and prolonging the opening time of the channel. Taken together, our findings support the emerging picture of a complex combinatorial pattern of co-expression of sensory neurochemicals, transducers and receptor components that help to define TG neuronal modality and function. We would advocate caution in making generalisations across sensory ganglia in particular in extrapolating data from the DRG to the trigeminal ganglion.

en_US
dc.language.isoenen_US
dc.publisherUniversity of Plymouthen_US
dc.subjectNeuroscienceen_US
dc.subjectPainen_US
dc.subjectTrigeminal ganglionen_US
dc.subjectInflammatory mediatorsen_US
dc.subjectNGFen_US
dc.subjectTrkAen_US
dc.subjectTNF-alphaen_US
dc.subjectp55en_US
dc.subjectIL-6en_US
dc.subjectgp130en_US
dc.subjectTRPV1en_US
dc.subjectTRPM8en_US
dc.subjectNociceptoren_US
dc.subjectHyperalgesiaen_US
dc.subjectExpressionen_US
dc.subjectPhenotypeen_US
dc.subjectPrimary cell cultureen_US
dc.subjectImmunohistochemistryen_US
dc.subjectImmunocytochemistryen_US
dc.subjectWestern bloten_US
dc.subjectElectrophysiologyen_US
dc.subjectCGRPen_US
dc.subjectNF200en_US
dc.subjectIB4en_US
dc.subjectDRGen_US
dc.subjectNeurochemicalen_US
dc.subjectNeuronal phenotypeen_US
dc.subjectNeuronal functionen_US
dc.subjectModalityen_US
dc.subjectPlasticityen_US
dc.subjectCapsaicinen_US
dc.titleDefining neurochemical properties and functions of primary sensory neurons in the rat trigeminal ganglionen_US
dc.typeThesis
plymouth.versionFull versionen_US
dc.identifier.doihttp://dx.doi.org/10.24382/4600


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