Doctors are examining whether migraines are linked to a common heart defect.
One in 10 Britons suffer migraines
One in four people have a valve-like hole, which can be closed using keyhole surgery, but it is twice as common among a type of migraine sufferer.
The study by Kings College Hospital in London and the Royal Shrewsbury Hospital will look at whether correcting the defect cures migraines.
Some 6m people in the UK have migraines, costing the economy £750m a year in lost production.
The heart defect, called a patent foramen ovale (PFO), often produces no symptoms.
In the womb, the opening is necessary to allow efficient circulation of blood and oxygen before the lungs start functioning.
After birth, it should fuse to produce a wall, or septum, separating the two atrial chambers. Sometimes, however, this does not occur correctly.
The theory is that closing this hole will ensure blood going through the heart is always filtered through the lungs on the way to the brain - thus removing chemicals that are thought to play a role in causing migraine.
The operation takes less than an hour and is carried out under light general anaesthetic.
A tube is inserted through a vein in the groin and worked through the blood vessels into the heart. A patch is then used to block the hole.
Researchers are now looking for volunteers who suffer migraines with aura - one of the most severe types of the condition.
Lead researcher Dr Andrew Dowson, director of the headache service at Kings College Hospital, said: "While there are many migraine treatments that help control symptoms, as yet there is no cure for migraine.
"If the trial supports our theories about a migraine-PFO link, it could be the most significant development in treatment for over a decade."
Dr Peter Wilmshurst, consultant cardiologist at the Royal Shrewsbury Hospital, who was one of the first doctors to make a link between the two conditions, said he hoped the study would help them improve understanding of migraines.
"It should help us to define the appropriate course of action for patients who experience migraine attacks and also have a PFO."
And Ann Turner, director of the Migraine Action Association added: "It is impossible for someone who has never experienced a migraine to understand its significant impact on a sufferer's quality of life - not just the attacks themselves, which are so painful and debilitating, but the constant fear of the next attack.
"This study could revolutionise the understanding and treatment of certain migraine headaches, but we must remain cautious until the trial is completed."
A spokeswoman for the Migraine Trust added: "At this stage it's much too early to have a clear picture on the efficacy of this procedure.
"There are many different types of migraine and many types of research into its possible causes. We will be watching all new research very closely."
Belinda Linden, of the British Heart Foundation, said: "There have been many reports about migraine affecting patients who have heart conditions such as a hole in the heart. Interestingly, there is also some evidence that migraine attacks can improve following successful treatment for a heart defect.
"These observations highlight the need improve understanding about the mechanisms that both trigger and relieve the migraine attack.
"Ultimately the findings may also help us understand more about migraine affecting the millions of people in the UK.