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Title: Sensory, cytokine and metabolic profiling of human experimental burn injury pain models
Author: Laycock, Helen Catherine
ISNI:       0000 0004 7427 7096
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Burn injury-associated pain represents a considerable burden to patients and is inadequately managed in the clinical setting. It is thought to be a consequence of the “burn-injury inflammatory soup” produced in the wound that activates and sensitises peripheral nociceptors. However the composition of this fluid and its interaction with peripheral nociceptors in incompletely defined, limiting the application of a mechanistic-based approach to burn injury-associated pain management. Two human experimental burn injury pain models (thermal injury and UVB injury) represent a potential opportunity to further elucidate these complex peripheral processes. Nonetheless controversy exists regarding their respective somatosensory phenotypes and the associated peripheral inflammatory protein and metabolic profiles remain uncharacterised. This thesis aimed to elucidate a more comprehensive understanding of the somatosensory changes and components of the “burn-injury inflammatory soup” with respect to inflammatory proteins and the metabolome. Forty-five healthy subjects had an experimental pain model imparted on their forearm (thermal injury, capsaicin injury or UVB injury models). Somatosensory testing and dermal microdialysis were performed. A multiplex microbead assay array was used to analyse dermal microdialysates to compare temporal within and between injury model inflammatory protein concentrations. Untargeted ultra performance liquid chromatography-mass spectrometry was used for global profiling of dermal microdialysates with the aim of determining significant compounds that separated injury models. Although some similarities were apparent in the three injury models with respect to secondary somatosensory changes and concentrations of the inflammatory proteins IL6, IL8 and CCL2, overall the three experimental pain models displayed distinct somatosensory, inflammatory protein and metabolic profiles. The UVB injury model appears to represent a less acute inflammatory reaction than is seen in the thermal injury model. Together these results support the use of the thermal injury experimental pain model to further investigate peripheral processes involved in acute burn injury-associated pain.
Supervisor: Bantel, Carsten ; Nagy, Istvan ; Takata, Masao ; Want, Elizabeth Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral