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Understanding the role of inflammation in cluster headache

Project details

Dr Anna Andreou
King's College London
Research area
Cluster headache
Funding type
Project grant
Awarded in
October 2021


Cluster headache is a rare and debilitating headache disorder, described as one of the most painful conditions known to man. The causes and underlying mechanisms of the disorder are not understood, limiting the development of effective treatments.

In this project, Dr Anna Andreou is studying the role of inflammatory and immune reactions in an area of the brain called the hypothalamus, to delineate their role in cluster headache.

Following rigorous assessment as part of our competitive grant round, this project was recommended for its importance in understanding cluster headache, and the insight it could give to the development of new treatments. With a strong project team, it has high potential for decisive results that will move the field forward.

About cluster headache

Cluster headache is a rare headache disorder, characterised by recurring bouts (clusters) of excruciating pain on one side of the head. It has been described as one of the most painful conditions known to man, with the intensity of the pain often reported to give rise to suicidal thoughts.

Cluster headache is a condition that impacts very heavily on the lives of patients and their families. The all-consuming pain and unpredictability of attacks can make it hard to carry on a normal life.

Whilst there are a number of different treatments that aim either to stop the pain during an attack or to stop the onset of attacks during a cluster, these are not effective in all patients.

Read more: About cluster headache

The role of inflammatory processes in the development of cluster headache

Aspects of cluster headache suggest that an area of the brain called the hypothalamus is involved in active headache clusters and attacks.

In this project the team is building on evidence that there is an immunological cause for this hypothalamic activation. They are aiming to delineate the involvement of specific hypothalamic inflammatory and immune reactions in the development of cluster headache attacks.

Specifically, they will investigate the role of a complex of proteins known as NF-kB, which are involved in a number of inflammatory processes.

Using well-established rodent models of cluster headache they will investigate the role of NF-kB – and other immune proteins whose production is influenced by NF-kB - in inducing cluster headache-like pain and associated symptoms. They will test the effectiveness of some different treatments in blocking the effect of NF-kB in the animal models.

They will also sample blood from people with cluster headache both during and in-between bouts to measure the levels of NF-kB and other immune proteins.

Studying headache in animal models

The mechanisms underlying cluster headache cannot be studied in humans because invasive approaches are required, including the removal of neural tissue for analysis.

Cluster headache is more than just a pain condition as attacks are accompanied by multiple symptoms that enable researchers to detect aspects of the onset of such symptoms in an animal.

The team is using a number of different headache models and techniques in this work in order to build as complete a picture as possible.

The use of animals is specifically addressed as part of our review process, to make sure that the use of animals is necessary, relevant and well-designed. All animal research carried out in the UK is tightly regulated by the Home Office and we require copies of the relevant licences before work can get underway.

Read our policy on the use of animals


Cluster headache is a poorly understood, excruciatingly painful condition. It has a terrible impact on the lives of those affected.

Whilst there are treatments available that offer some relief for some patients, many people struggle to get relief.

This research will shed new light on the processes underlying cluster headache to accelerate the development of new treatment approaches.

About the team

Dr Anna Andreou is leading headache research at the Headache Research Lab within the Wolfson Centre for Age-Related Diseases, King's College London and the Headache Centre, Guy’s and St Thomas’ NHS Trust. She has extensive experience in animal models of headache and pharmacological investigations.

She will work with colleagues Dr Giorgio Lambru, Clinical Lead of the Headache Centre, who has extensive experience in the diagnosis and treatment of cluster headache, and Dr David Andersson, King's College London, who runs a programme of research focused on the role of inflammation in pain, with wide-ranging experience in the use of animal pain models.

Together, this team is well-placed to deliver on the objectives of this innovative project.

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