D.Phil. Faculty of Health Sciences, University of the Witwatersrand, 2009 / In this thesis I describe the development of an animal model of sustained hyperalgesia
induced by exposure to ultraviolet (UV) A light to the rat’s tail, and the role of the Cfibre
barrage and peripheral afferent fibre sensitization in this model of hyperalgesia.
Exposure of rats’ tails to UVA-light caused hyperalgesia to a noxious thermal
challenge, immersion of the rats’ tails into 49°C water, and a noxious mechanical
challenge, application of a static force of 3.9N by a bar algometer onto the rats’ tails.
The hyperalgesia to the thermal challenge lasted eight days and hyperalgesia to the
mechanical challenge continued for up to 16 days. Despite the sustained hyperalgesia,
rats exposed to UVA-light showed no overt signs of morbidity as they gained weight
normally and were mobile throughout the study. Histological examination of rat tail
tissue showed mild, chronic inflammation in rats exposed to UVA-light and in rats that
had their tails covered with a protective layer of aluminium foil during UVA-light
exposure. This inflammation was therefore not responsible for the behavioural
hyperalgesia.
To investigate the role of C-fibre barrage in the development of hyperalgesia after
UVA-light exposure, I pre-emptively blocked C-fibre activation during UVA-light
exposure with the local anaesthetic bupivacaine. Injection of bupivacaine (1ml of
0.5%), into the base of the tail prevented the development of thermal hyperalgesia to
tail immersion in 49°C water. However, it did not prevent the development of
hyperalgesia to a noxious punctate challenge. Thus the sustained mechanical
hyperalgesia did not depend on the activation of the C-fibre barrage, but thermal
hyperalgesia did depend on the activation of a C-fibre barrage during the conditioning
event of UVA-light exposure.
Lastly, in rats anaesthetised with enflurane, I examined the responses of coccygeal
primary afferent fibres to noxious thermal and mechanical stimulation after UVA-light
exposure of their receptive fields on the tail. I investigated only pure nociceptive
afferents and ignored those afferents that responded to challenges in the noxious and
non-noxious ranges. The peak firing rates and areas under the curve of post-challenge
histograms, a measure of neuronal firing over time, of Ad- and C-fibres were
increased when noxious blunt and punctate challenges were applied to the rats’ tails
after UVA-light exposure, showing that Ad- and C-fibres that encode for noxious
mechanical challenges were sensitized. The peak firing rate of C-fibres that were
responsive to noxious thermal challenges were not increased after UVA-light
exposure. Therefore, thermal hyperalgesia was probably mediated by sensitization of
central nervous system neurones.
In summary, I developed a model of sustained mechanical and thermal hyperalgesia
caused by UVA-light exposure of the rat tail. The thermal hyperalgesia was initiated
by the C-fibre barrage, while mechanical hyperalgesia did not depend on the C-fibre
barrage and peripheral afferent sensitization of Ad- and C-fibres could account for the
mechanical hyperalgesia.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7207 |
| Date | 08 September 2009 |
| Creators | Themistocleus, Andreas Constantinos |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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