The Conserved Genetic Architecture of Pain

Abstract

Evolutionary models such as Drosophila have proved powerful for the interrogation of many peripheral nervous disorders including in motor neuron disease and pain. Given the evolutionary conservation of the peripheral nervous system, model organisms provide a powerful tool for the investigation of pain. Here we demonstrate several vignettes that show firstly, how relatively simple organisms can provide rapid models to assess and understand Mendelian disorders. We then show how simple models can be interrogated to identify central druggable pathways to develop a new stem cell therapy. Finally, we utilise the evolutionary conservation between mammalian species to validate developmental pathways and apply these to a therapeutic context. We apply this approach to a significant problem, pain. Throughout this thesis we apply new technologies to identify potentially druggable pathways and utilise simple organisms to test and validate them. Through our literature review, we firstly provide an overview of the central knowledge of pain perception, chronic pain, approaches to its treatment, the genetic basis of rare pain disorders and finally approaches to modelling pain. Secondly, we approach epigenetics, and assess the central mechanisms of epigenetics followed by an assessment of its role in pain perception.