Clemente, Elisa De Sequeira Couto E Vazão;
(2022)
Establishing the zebrafish as a model to study the genetics of nociception.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Pain is crucial for survival, and the ability to detect potentially harmful stimuli and respond accordingly is evolutionarily conserved. However, pain can also be undesirable in several situations, such as chronic pain. Pain management represents an unmet clinical need, with promising drugs identified in pre-clinical studies in rodents often failing to produce analgesia in clinical trials. This highlights the need for a better understanding of the mechanisms underlying the processing of noxious stimuli. The zebrafish has been increasingly used as an animal model in various fields. In this study, I aimed to establish the zebrafish as a model to study the genetics of nociception. I first established an infrared laser assay to deliver temporally precise noxious heat stimuli, and studied the behavioural responses of tethered zebrafish larvae upon stimulation. I found that there are two components in these responses, which are temporally separated, have different properties, and can be modulated using chemicals. Then, I generated zebrafish F0 knockouts of ngfb, ntrk1 and prdm12b, the zebrafish orthologs of three genes known to play a critical role in human pain, both physiologically and pathologically. I observed anatomical defects in a subset of ntrk1 and prdm12b mutants. ntrk1 mutants that lacked anatomical defects showed no changes in their response to noxious heat. However, I found that the fast component of the response to the laser was nearly completely abolished in ngfb mutants which were otherwise normal. A genetic approach to the study of zebrafish nociception can be used to gain a mechanistic understanding of the genes, cells and pathways involved in sensing noxious stimuli and generating protective behaviours, which may help the development of better drugs and treatments for pain.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Establishing the zebrafish as a model to study the genetics of nociception |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10159061 |
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