Project ID NS-MH2024_33


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Centre for Age-Related DiseasesWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Centre for Age-Related DiseasesWebsite

Unmasking Migraine: Investigating Sex-Differences and Novel Therapies through Cellular and Animal Models

Women are up to three times more likely than men to have migraines, making migraine the leading cause of disability in young females. For approximately half of women aged 18-60, the onset and timing of migraines is associated with hormonal fluctuations and their menstrual cycle. Despite this gender-gap, little has been done to explore the nature of sex-related differences in migraine and their clinical consequences. Our preliminary research has identified key mechanisms that influence this gender-gap, exploring how hormones interact with key cells and neural circuits to make women more susceptible to this disabling condition.

The project will:

1. Use cutting edge in-vitro cellular approaches to determine sex-specific mechanisms responsible for sensitising migraine-related pain (0-18 months).
2. Investigate the most promising outcomes from the cellular models in validated animal models of migraine, ensuring promising mechanisms are explored from cells to circuits (10-28 months).
3. Explore intervention strategies (e.g. pharmacological/chemogenetics) to uncover novel therapeutic targets (months 24-36) that can be translated into the clinic to reduce the significant gender-gap in migraine burden.

Key translational aspects will be explored via established clinical collaborations as appropriate. The successful student will develop state-of-the-art in-vitro (e.g. “lab on a chip” microfluidic chamber) and in-vivo (e.g. surgery, electrophysiology, viral tract tracing, chemogenetics and behavioural approaches), ensuring they master a number of highly desirable specialist skills above and beyond standard laboratory procedures. As specific aspects of this project require work with animal models the candidate will be required to obtain a Home Office personal licence (months 0-6). However, this is not required for the in-vitro component of the project. The successful student will join a collaboration between two vibrant groups in the world leading pain centre at the Wolfson Centre for Age-Related Disorders and be exposed to cutting edge translational research that aims to tease apart the molecules, cells and circuits underlying the increased occurrence of migraine in women. In part, helping to redress the significant gender-bias that exists in this highly disabling neurological disorder.

Representative Publications

The selective 5-HT1F receptor agonist lasmiditan inhibits trigeminal nociceptive processing: Implications for migraine and cluster headache. Vila-Pueyo, M. et al. 2022. Br J Pharmacology. DOI: 10.1111/bph.15699.

A cell atlas for migraine research. Holland, P.R. and Goadsby, P.J. 2022. Nature. DOI: 10.1038/d41586-022-01479-4.

Differential medication overuse risk of novel anti-migraine therapeutics. Saengjaroentham et al. 2020. BRAIN. DOI: 10.1093/brain/awaa211.

Kimourtzis, G., N. Rangwani, B. J. Jenkins, P. A. McNaughton and R. Raouf (2022). “A microfluidic-based model of nociceptor sensitization reveals a direct activation of sensory axons by prostaglandin E2.” bioRxiv: 2022.2003.2018.484883.

Vysokov, N., S. B. McMahon and R. Raouf (2019). “The role of Na(V) channels in synaptic transmission after axotomy in a microfluidic culture platform.” Sci Rep 9(1): 12915.

Tsantoulas, C., C. Farmer, P. Machado, K. Baba, S. B. McMahon and R. Raouf (2013). “Probing functional properties of nociceptive axons using a microfluidic culture system.” PLoS One 8(11): e80722.