Improving the principles of the 3Rs through new integrative metabolomic and gene expression resources for signalling studies in burn injuries

Burn injury-associated pain is an excruciating type of pain that is often compounded by a lack of successful pain control. In order to develop better pain control in burn injuries, a more detailed understanding of the molecular basis of burn injury-associated pain is required. Mechanistically, such pain is believed to be mediated by poorly characterised biologically active substances that accumulate in burn-injured tissues during tissue damage which, in-turn, cause inflammatory processes that activate and/or sensitise nociceptive sensory nerve fibres in and around the injured area through cell receptors. Here, we aim to create a comprehensive new integrative biological resource defining the metabalome of burn injured tissues, and of gene expression profiles of primary sensory neurons (PSN), all of which will be made available to the research community to promote further studies of the molecular basis of burn injury-associated pain. Using state-of-the-art high resolution technologies, this study will provide more relevant, reliable and detailed information using significantly reduced numbers of animals than conventional hypothesis-driven studies. Further, this study will represent a significant improvement in refinement, as animal subjects will not experience pain, suffering or distress. Finally, this study will also define a significant improvement in replacing studies on live animals, as gene expression studies will use cultured PSN. We believe that the databases we will generate will be valuable resources that will significantly contribute to improving the 3Rs across pain and burns research.