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A new approach to treatment of migraine

Project details

Researcher
Professor Peter McNaughton
Institute
King's College London
Research area
Migraine
Headache and facial pain
Funding type
Project grant
Awarded in
September 2018
Completion
Ongoing
March 2021

Introduction

Migraine is a complex condition that is estimated to affect more than 10 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.

Migraine has a variety of symptoms, most notably a painful headache. Other symptoms include disturbed vision, sensitivity to light, sound and smells, as well as nausea and vomiting.

There is no cure for migraine, but existing treatments can reduce the severity of attacks in some people, and steps can be taken to reduce the likelihood of attacks occurring.

In this project, Professor Peter McNaughton pursued a new idea of how migraine pain may develop and, hence, how it may be treated.

About migraine

HCN2 channels: a novel target for treatment of migraine

Pain is initiated when specific pain-sensitive nerve fibres (nociceptors) are activated by painful stimuli - such as heat, sharp force, and chemical stimuli such as acid.

In the last 10 years, progress has been made in understanding the biological changes that are triggered by contact with these stimuli. In the case of migraine, however, it is not clear how the various stimuli that are associated with the condition actually cause the symptoms.

Peter McNaughton is Professor of Pharmacology at King’s College London. He leads a programme of research focused on pain, and uses molecular and cellular techniques to study the processes underlying pain sensation. His lab is at the forefront of research into pain.

In this project, he proposed a new and original idea of how migraine pain may develop and hence, how it may be treated. Supported by a solid body of preliminary work, the project focused on a protein called HCN2, part of a family of proteins called HCN ion channels. Ion channels are “tiny transportation tunnels” in cell walls. They play an essential role in nerve conduction and neural communication. Malfunction of ion channels can cause enhanced pain sensation in a number of pathological pain conditions such as nerve damage and shingles.

Professor McNaughton proposed that HCN2 may essentially be the gate-keeper to migraine and, accordingly, that blocking it could alleviate migraine symptoms.

This project took forward this previously unexplored role for HCN2 in migraine. The team used mouse models of migraine, in which a migraine-like state is induced by administration of a known migraine trigger. They found that HCN2 controls the electrical activity of the trigeminal neurons, nerves that are responsible for transmission of sensory information from the face and jaw to the brain. Increased HCN2 activity promotes electrical firing of these neurons, and thus triggers migraine-like pain. When they removed the HCN2 gene from trigeminal neurons, they found that the mice did not develop migraine-like pain.

This is the first time that HCN2 ion channels have been shown to drive migraine-like pain, and these results therefore open up a potential new target for future migraine treatment.

Impact

Migraine is a distressing and debilitating condition from which many sufferers struggle to achieve effective relief.

It takes a heavy toll on the lives of individual sufferers, impacting relationships and family life, work and wider health. It impacts enormously on society as a whole, through lost productivity.

Current treatments are not effective for all and are associated with a variety of side effects.

By identifying a potential new target for migraine therapy, we hope that this work will ultimately translate through to new treatment options for patients suffering from this common disorder.

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