Oakley Morgan was awarded a Brain Research UK PhD studentship in 2018, to enable her to pursue research focused on the relationship between stress and pain disorders, including migraine.
She worked under the supervision of Dr Sandrine Géranton, a leading expert in the molecular biology of pain and the role of the protein FKBP51 in persistent pain. Together they have provided new insight into the mechanisms underlying the relationship between stress and pain.
Following successful completion of an ambitious programme of research, Oakley was awarded her PhD from UCL in June 2023.
Migraine is a complex condition that is estimated to affect around 11 million people in the UK. It is more prevalent than diabetes, epilepsy and asthma combined and, because of its prevalence, is one of the leading causes of disability among the neurological disorders. It is poorly treated by current therapeutics.
Migraine has a variety of symptoms, most notably a painful headache. Other symptoms include disturbed vision ('aura'), sensitivity to light, sound and smells, as well as nausea and vomiting.
The chronic form of migraine affects up to two per cent of the population, and is defined as having more than 15 headache days in a month, of which at least eight have migraine features.
Our limited knowledge of the underlying causes of migraine makes it a difficult condition to manage. Stress is known to trigger migraines, and exacerbate other pain conditions, but the reasons are not clear. Oakley set out to shed light on the mechanisms underlying this relationship between stress and pain during her PhD research.
Stressful life events are known to exacerbate chronic pain states, and this is particularly true among chronic migraine sufferers. Stressful life events often trigger migraine attacks in those adults who suffer from migraines, while exposure to adversity in childhood has been shown to be more prevalent in adults with migraine.
However, despite the known impact of stress on pain, such as with migraine, the biological mechanisms underlying their interaction are not established.
A protein called FKBP51 was already known to be involved in the regulation of stress and, independently, persistent pain. Whether this protein was key to the connection between the two was not known.
Working under the supervision and guidance of Dr Géranton, Oakley set out to explore the relationship between stress and migraine. She aimed to determine whether blocking FKBP51 could decrease migraine pain, and whether it could modulate the effect of early life stress on the susceptibility to chronic migraine.
To address these questions, the team combined animal (mouse) models of stress and pain. They looked at the relationship between stress exposure in both adulthood and early life, and later pain experiences. They found that stress alone caused a whole-body sensitivity in mice and that stress-exposed mice showed worse pain responses after injury. Crucially, the pain lasted longer when combined with stress. Other symptoms such as anxiety were also exacerbated in the stress-exposed mice.
They then blocked FKBP51 to see what effect this had on pain responses. They found that blocking FKBP51 prevented the prolongation of mechanical pain in the stress-exposed mice, as well as the development of pain-related emotional symptoms. This suggests that FKBP51 was indeed driving this effect.
Further experimental work provided evidence for the involvement of epigenetic mechanisms that appear to link stress with a predisposition to chronic pain development; the regulation of expression of the gene that regulates production of the protein FKBP51 is altered by stress exposure, and this is associated with a predisposition to chronic pain development.
Migraine and other chronic pain conditions are often debilitating and have a significant negative impact on quality of life.
Existing treatments are effective for only a small population of those affected, and if we are to work out how to treat the conditions more effectively, we need to understand the underlying disease mechanisms.
Oakley's research helps to shed light on these mechanisms. Her work has provided a greater understanding of the relationship between stress and pain, providing the first evidence for a role of FKBP51 in both conditions and opening up the possibility of using it as a treatment target.
Having been awarded her PhD in June 2023, Oakley has now taken up a position at McGill University in Montreal, working with renowned pain scientist Professor Jeffrey Mogil. The work that she started during her PhD will be continued in the labs of her PhD supervisor, Dr Sandrine Géranton.
I developed a great number of skills during my time as a PhD student, via academic training courses, in lab technical training, as well as communication and career development courses and conferences. Each have benefited me greatly as I transition on to the next steps of my career and for this I am extremely grateful to Brain Research UK.
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