Making migraine less of a pain

Researchers establish that vagus nerve stimulation is effective in suppressing cortical spreading depression, a trigger for migraine

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VALENCIA, Spain—A poster presentation at the 17th Congress of the International Headache Society in Valencia, Spain, reported that vagus nerve stimulation (VNS) inhibits cortical spreading depression (CSD), which is known to be the cause of migraine aura and a trigger for headache. A brief VNS reduces CSD in less than 30 minutes and lasts for more than three hours, acting much more quickly than traditional, pharmaceutical, prophylactic migraine treatments.
CSD is a local disturbance in the occipital cortex region of the brain, which is caused by a slowly propagating wave of depolarization—suppression of electrical activity—spreading across the cortex.
The researchers determined that both surgically implanted and non-invasive VNS were just as effective at reducing CSD. They also found that VNS reduced CSD in 20 to 30 minutes as against the standard migraine prophylactic drugs, which took weeks to have a similar effect.
Dr. Cenk Ayata, a professor at Harvard Medical School and Massachusetts General Hospital, commented, “What we have established is that VNS reduces the hyper-excitability of the brain by suppressing CSD and that VNS is much quicker at achieving this than traditional migraine prophylactic agents such as topiramate and valproic acid. We were also able to establish that VNS was effective in reducing CSD for at least three hours after only four minutes of treatment. Our findings have opened up exciting possibilities for further research.”
Reducing CSD is the validated platform for screening pharmacological therapies for migraine with aura. Many preventative migraine drugs, regardless of pharmacological class, inhibit CSD.
The preclinical study had four arms: non-invasive VNS, surgically implanted VNS, sham group where electrodes were implanted but never stimulated and naive animals. CSD was elicited by either a continuous KCI application or by electrical stimulation.
CSD was then measured in all groups, and it was found that VNS raised the electrical threshold to initiate CSD by more than threefold and reduced the frequency and speed of the continuous KCI-induced CSDs. Both non-invasive and surgically implanted vagus nerve stimulation were equally effective in reducing CSD.
Blood pressure and heart rate were also continuously monitored and were only minimally and transiently affected by VNS.
The authors believe that VNS works by modification of specific brain pathways—specifically monoaminergic pathways, which are the networks of neurons that utilize monoamine neurotransmitters and are involved in the regulation of cognitive processes such as emotion, arousal and certain types of memory—neurotransmitters and cytokines. Cytokines include a number of substances, such as interferon, interleukin and growth factors, which are secreted by certain cells of the immune system.
A full paper on this research will be published in a scientific journal by the end of the year.
This work was funded in part by the American Heart Association, the Massachusetts General Hospital and an unrestricted research gift from electroCore LLC. electroCore, founded in 2005 in New Jersey, is focused on developing non-invasive vagus nerve stimulation self-administered therapies for the treatment of multiple conditions in neurology, psychiatry, gastroenterology and the respiratory field. The company’s initial target is the treatment of primary headaches (migraine and cluster headache) and the associated chronic co-morbidities of gastric motility, psychiatric, sleep and pain disorders that drive disproportionately large direct and indirect costs within the healthcare system and society.

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