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.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2006. / Härtill 4 uppsatser.

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<p>Ultraviolet radiation (UV-R) is an environmental factor known to increase the risk of developing an irreversible opacification of the lens (cataract). Increased irradiance of UV-R to the earth because of depletion of stratospheric ozone is of current concern considering cataract formation. Detailed metabolic information from the cornea, lens and aqueous humour might give valuable knowledge on the biochcemical processes occurring in the eye after exposure to UV-R, and thereby a better understanding of the mechanisms by which UV-R induces cataractogenesis. The purpose of this thesis was to study metabolic effects of exposure to UV-R on the anterior part of the eye. Effects of UV-B (280-315 nm) and UV-A (315-400 nm) on the aqueous humour, cornea and the lens from animal models were investigated by ¹H nuclear magnetic resonance (NMR) spectroscopy. Since the lens is composed of functionally distinct anatomical compartments, with different metabolic activity, biochemical changes in various compartments of the lens were analyzed.</p><p>Application of NMR-based metabonomics was effective to analyze metabolic changes in the anterior part of the eye after exposure to UV-R. High-resolution (HR) magic angle spinning (MAS)¹H NMR spectroscopy provided high quality spectra from intact tissue of cornea and lens, and provided important information about metabolic alteration occurring in these tissues after exposure to UV-R. The results from this thesis show that in vivo UV-B radiation affects metabolism of the anterior compartments of the eye. Metabolic changes were observed in aqueous humour, cornea, lens and in the different compartments of the lens. The antioxidants, glutathione and ascorbate, several amino acids, high energetic phosphates, and compounds important for membrane building and osmoregulation were substantially altered after exposure to UV-B radiation. Several biochemical effects such as oxidation, membrane disruption, osmoregulatory problems, lipid peroxidation, problems with cellular signalling and impairment of growth and protein synthesis were suggested. After UV-A exposure, no observable metabolic alterations were found in the anterior part of the eye in the present animal models.</p>

Ultraviolet radiation (UV-R) is an environmental factor known to increase the risk of developing an irreversible opacification of the lens (cataract). Increased irradiance of UV-R to the earth because of depletion of stratospheric ozone is of current concern considering cataract formation. Detailed metabolic information from the cornea, lens and aqueous humour might give valuable knowledge on the biochcemical processes occurring in the eye after exposure to UV-R, and thereby a better understanding of the mechanisms by which UV-R induces cataractogenesis. The purpose of this thesis was to study metabolic effects of exposure to UV-R on the anterior part of the eye. Effects of UV-B (280-315 nm) and UV-A (315-400 nm) on the aqueous humour, cornea and the lens from animal models were investigated by 1H nuclear magnetic resonance (NMR) spectroscopy. Since the lens is composed of functionally distinct anatomical compartments, with different metabolic activity, biochemical changes in various compartments of the lens were analyzed. Application of NMR-based metabonomics was effective to analyze metabolic changes in the anterior part of the eye after exposure to UV-R. High-resolution (HR) magic angle spinning (MAS) 1H NMR spectroscopy provided high quality spectra from intact tissue of cornea and lens, and provided important information about metabolic alteration occurring in these tissues after exposure to UV-R. The results from this thesis show that in vivo UV-B radiation affects metabolism of the anterior compartments of the eye. Metabolic changes were observed in aqueous humour, cornea, lens and in the different compartments of the lens. The antioxidants, glutathione and ascorbate, several amino acids, high energetic phosphates, and compounds important for membrane building and osmoregulation were substantially altered after exposure to UV-B radiation. Several biochemical effects such as oxidation, membrane disruption, osmoregulatory problems, lipid peroxidation, problems with cellular signalling and impairment of growth and protein synthesis were suggested. After UV-A exposure, no observable metabolic alterations were found in the anterior part of the eye in the present animal models.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Thesis (M.Sc.). / Written for the Dept. of Biochemistry. Title from title page of PDF (viewed 2008/01/15). Includes bibliographical references.

Thesis--Catholic University of America. / Reprinted from Transactions of the American Microscopical Society, v. 78, no. 2-3, 1959.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 68-74).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1923. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 36-38).