Filling In The Map On Migraine

The future for people with migraines looks promising.

Our understanding of migraine pathophysiology is accelerating rapidly. 

Migraine is no longer considered strictly a vascular headache. It can now be described as a neurovascular headache. We are also learning more about the difference between aura and migraine, and about the links between migraine and tension headache. New and targeted treatments are available or will be soon.1

People with migraine may inherit a vulnerability to triggers that initiate the condition’s neurovascular cascade. It may begin with a prodrome that includes a vague sense of anticipation starting up to 24 hours before an aura.

“It is important for an understanding of migraine to distinguish migraine with aura from migraine without aura,” said Stewart Tepper, MD, professor of medicine and neurology at the Cleveland Clinic Lerner College of Medicine. “About 80% of people with migraine do not have an aura, and some people may have an aura without a migraine. It may be best to think of aura and migraine as parallel tracks instead of a single track.”

An aura is currently thought of as a spreading march of neuronal activation. This march may be reversible and may or may not precede a migraine. The term used to describe this march is cortical spreading depression (CSD). 

“That term is a bit of a misnomer since what we see is a wave of activation, not depression. Think of it as an inherited hyperexcitability of the brain. Neurons are firing in a low wave across the cortex,” said Tepper. The aura may appear as the march crosses the cortical areas responsible for vision, sensation, and language. 1

The Headache

Researchers know a lot more about the generation of migraine pain, but there are still areas that need to be explored.

 “Anyone who tells you they know where the generation starts is uninformed. It could be central, [or] it could be CSD. It could be brain stem, [or] it could be the trigeminal ganglion,” Tepper said. 

Wherever the genesis comes from – and it may come from more than one place – the result is a cascade of inflammation and vasodilation. The most likely cause of the actual pain is meningeal blood vessels. 

“The million dollar question is, ‘Where does the process start?’ It could be in the meninges. The meninges may stimulate the trigeminal nerve, and afferent pathways of the trigeminal nerve could be the key pathway,” Tepper said. 1

Are Migraine and Tension Headache Linked?

A 2015 study published in the journal Pain suggests that tension headache and migraine may be two points on the same continuum. 

The study evaluated headache symptoms in more than 3,000 patients. Researchers concluded that the overlap between migraine and tension headache is quite significant in young adults with frequent headaches. 2

Is there enough evidence to say that tension headache may be a type of migraine? 

“I believe that this question is best posed as its opposite: What is the evidence that tension headache and migraine are distinct categories based on either experience or basic pathophysiology?” said Dana Turner, MSPH, and lead investigator of the study.

“Our data do not support the diagnostic distinction in many patients. We observed that for many patients, the symptoms that have been proposed to define each category overlap substantially, with individuals diagnosed with migraine experiencing many of the symptoms of tension headache and vice versa,” explained Turner. 

“There are three current thoughts on this. Tension and migraine may be the same. They may be completely different, or some tension headaches may be migraines. The evidence seems to be pointing to two types of tension headaches. One type is just tension. The other type is a baby migraine,” said Tepper. 

“If we can replicate these results, the idea that the experience of headache can be considered as a continuum of severity has profound implications for diagnosis, treatment, and communication among sufferers and providers,” Turner said. 

New Treatments?

Calcitonin-gene-related peptide (CGRP) may be the key to targeted migraine treatment and possibly to treatment of other severe headaches. There is growing evidence that if you block this potent peptide you can block the cascade of migraine. 1

“CGRP antagonists have been tried. They seemed to work, but they caused liver damage. Now we have monoclonal antibodies to block CGRP. Evidence suggests that blocking CGRP with antibodies in the meninges alone is sufficient to prevent a migraine,” said Tepper. 

There are two other new frontiers of treatment. There are improved delivery systems for traditional ergots and triptans, and noninvasive devices that interrupt auras or migraines with neurostimulation. “The new delivery systems are old wines in new bottles, but the new devices are really exciting,” said Tepper. 

For example, Cefaly is the first transcutaneous electrical nerve stimulator approved for migraine prevention. Cefaly is a battery-powered headband that sends out pulses to stimulate branches of the trigeminal nerve. Other than a tingling sensation, there are no reported side effects. Studies show users who wear the device for 20 minutes a day have significantly fewer migraine attacks and require less migraine medication. 3 

So stay tuned – the future for migraine sufferers looks promising.


  1. American Headache Society. Pathophysiology of Migraine.

  2. Turner DP, et al. Pain. 2015; DOI: 10.1097/j.pain.0000000000000157

  3. FDA. FDA allows marketing of first medical device to prevent migraine headaches.