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Title: The development and validation of a murine model for studying the role of histamine receptors in acute and chronic itch
Author: Bell, Jonathan K.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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The present studies were undertaken to develop and validate acute and chronic models of itch in mice, based on the combined use of behavioural tests in awake mice and in vivo electrophysiological recordings from itch afferents in anaesthetized animals. The hypothesis was that scratching behaviour can be evoked in mice using intradermal injections of pruritogenic drugs and that this can be measured automatically and objectively to provide a reliable indicator of itch. A further hypothesis was that electrophysiological recordings made in vivo from murine cutaneous sensory nerves can be used to distinguish between pruritogens and algogens. The model of itch that was developed is based on injection of histamine into the back of the mouse neck to evoke scratching of the area by the hind paws. The studies demonstrated that scratching in mice can be induced using histamine and other pruritogens (e.g. trypsin and 5-HT) in a reproducible dose dependent manner. Scratching was established as a response to itch-provoking agents, but not to painful stimuli. A novel mechanism of histamine evoked scratching involving H4 receptors was discovered. Chronic itching in response to topical application of dinitrochlorobenzene was also established. A robust automated method for the detection and measurement of scratching in mice was developed, which considerably enhances accuracy and reduces the time taken, in comparison with manual observation of scratching. In vivo electrophysical recordings showed that pruritogens evoke a pattern of response in cutaneous nerves distinct in nature from that evoked by algogenic stimuli. However, nerves responded to both stimuli, suggesting that in mice, there are probably no independent ‘pruritoceptos’, unlike the situation in man. In summary, scratching in mice can be recorded automatically and used as a reproducible quantitative measure of itch.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available