Migraine is a severe debilitating neurological disorder and we and others have demonstrated that it is a brain disorder resulting in dysregulation of sensory processing, pain and multisensory hypersensitivity (e.g. to light, sound and touch). Despite this, many anti-migraine therapeutics primarily target peripheral sites of action and act to mask this pain as oppose to targeting the mechanisms underlying this central dysregulation directly. Importantly, we have recently demonstrated that novel CGRP-targeted therapies can help to reduce sensory hypersensitivity in people with migraine, while CGRP expressing neurons in the thalamus play a key role in the integration of multi-sensory threat cues. While CGRP receptors are expressed throughout the brain, the role of blocking CNS CGRP receptors and other central targets remains unknown as many of the current therapies are considered to have limited CNS access. In the current proposal, we will explore CNS targets of multisensory integration, including the thalamus, determine the underlying mechanisms of sensory integration and explore novel CNS-acting therapeutic targets for migraine. Given the impact of sensory hypersensitivity on patients’ physical and mental well-being, we will work collaboratively with the Migraine Trust to optimise patient involvement, research impact and dissemination, ensuring rapid real-life impact of our research.
The student will gain experience in state-of-the-art in-vivo behavioural and molecular techniques, including in-vivo electrophysiology and micro-iontophoresis which are recognised vulnerable skill sets by UKRI. This will be complimented with training in public engagement, policy, research impact and dissemination, enhancing the relevance, acceptability and impact of the research. Taken together, the current proposal will ensure that the successful applicant gains diverse training beyond the laboratory and ensuring that they are best placed to develop their research pathway based on real-world needs and priorities, leading to more effective and meaningful research outcomes.
The project will:
Year 1 – 2: Investigate the mechanisms of multisensory integration and the impact of dysregulation of sensory processing in migraine.
Year 2 – 3: Explore the underlying mechanisms of sensory integration in migraine-relevant animal models.
Year 2.5 – 4: Explore novel CNS-acting mechanism-based therapeutic targets to normalise dysfunctional multisensory integration in migraine.
Year 1 – 4: Embed patient involvement in the research programme and receive targeted training in research policy and impact, including participation in the UKRI policy internship scheme (3 months, year 2 or 3).
The successful candidate will join the world leading Wolfson Sensory Pain and Regeneration Centre (WSPaRC) at King’s College London and be required to obtain a Home Office personal licence within the first 6 months if not currently in place.
