Project 3.2: Discovery for the basis of fibromyalgia

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Fibromyalgia is an incurable condition characterized by chronic widespread pain, fatigue, mood disorders, anxiety and stress. Despite that over 2% (>80% of which are women) of the population has fibromyalgia, the cause and mechanisms responsible have remained unknown and no effective therapies or diagnostic tests are available. The supervisors' recent work will transform our view of fibromyalgia. We have discovered that fibromyalgia is an autoimmune condition in which pain-sensing neurons are hyperexcitable and we are now exploring how autoimmunity causes pain. This studentship presents a rare opportunity to discover the mechanisms responsible for a common disease. The project is based on "passive transfer" of fibromyalgia, where administration of patient samples transfers symptoms from patients to mice, the most direct form of translational medicine. During the first 12-18 months, behavioural assays of muscle-strength, activity and pain sensitivity will determine which types of symptoms can be transferred from fibromyalgia patients to mice. In parallel, immunohistochemistry, in situ hybridization and proteomics will be used to identify the neurons and molecules targeted after transfer of fibromyalgia from patient to mouse. During the remainder of years 2-3, pharmacological interventions, knock-down strategies and transgenic approaches will be used to interfere with cells and molecules identified during the first phase of the project. These experiments will evaluate the therapeutic potential of interventions against symptoms caused by the human pathogen. Year 4 will be spent completing experiments, writing manuscripts, thesis and fellowship applications. The student will be encouraged to present findings at national and international meeting.