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Another Clue into How Migraine Works

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A study in JAMA published in August confirms yet another probable link in the migraine chain – something called vasoactive intestinal polypeptide (VIP).

VIP is a peptide hormone found naturally in the body. As an article in AJMC states, “Once the trigeminovascular system is activated, afferent and efferent nerve fibers release various VIPs, which stimulate G-protein coupled receptors (GPCRs).” The trigeminovascular system, the neurons in the trigeminal nerve in your face, are often associated with headache. So what do VIPs have to do with headache pain? Are they just incidental, or are they an important part of the migraine attack?

This particular study simply injected patients with VIPs to see if it would result in migraine headache symptoms. (Don’t worry – patients were warned that they might get a headache. But they didn’t know if they were getting a VIP injection or a placebo.)

71% of patients injected with VIP (and 5% – one patient with placebo) did indeed develop headache. This would seem to confirm that VIP does actually play an important role in the headache chain reaction.

But why? It could have to do with the messages VIP sends to blood vessels, causing them to dilate. Vasodilation does often occur in migraine attacks.

The purpose of this study was to see if VIP may be a target for future migraine treatments. In fact, several pharmaceutical companies were providing funding to some of the researchers in the study.

As we have discussed before, there are many things that happen in the body during a migraine attack. Finding one link in the chain, or one part of the puzzle, may help us find better treatments. But it’s probably a long way from truly understanding the root of migraine, and discovering a “cure”.

For more, check out this article from AJMC: Study Suggests Vasoactive Intestinal Polypeptide May Induce Migraine

A Migraine Mystery (You’ll never guess this one…)

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You’ve heard it before.  And intuitively, it seems true.

Something starts the migraine chain-reaction.  Ok, maybe we’re not sure exactly how that works.  But then the blood vessels expand and constrict, the inflammation starts.  And as your heart beats and the blood forces its way through your body, it brings on the POUND POUND POUNDING pain of a migraine headache.

But, have you ever really thought about whether that’s actually true?

Throbbing pain is, of course, a typical characteristic of migraine.  It’s one of the ways that we recognize migraine as opposed to other types of headache.  In fact, in the most recent headache classifications from the International Headache Society, in order to be diagnosed as migraine the pain must have at least two of these characteristics:  one-sided pain, pulsating, moderate or severe pain, and aggravated by activity.

But as with so many realities of headache disorders, when researchers actually investigate, they find that the mystery deepens.

For one thing, we have discovered that the constriction and dilation of blood vessels is not always a clear process when it comes to migraine.  Advanced imaging studies are discovering that vasodilation, formerly the cornerstone of migraine research, is not a necessary part of migraine after all.  (See also this study and Vasodilation and Migraine – The fall of a theory)

Although blood vessels are clearly and necessarily a part of our study of migraine, they may not be related in the way we formerly believed.

And that brings us back to that pulsating pain.

What would happen if we did the obvious, and compared the movement of blood through the body, the heart beat, the pulse, with the throbbing?  Well, now we know.  It looks something like this…

Throbbing Pain vs Pulse

Notice anything odd?  That’s right, the pulse and the pulsating pain don’t match.  In this case, the throbbing pain was slower than the pulse.  This was typical.  But even in patients where the rate of the throbbing and the pulse were similar, they went in and out of sync.

This study (On the temporal relationship between throbbing migraine pain and arterial pulse.) and others are sending researchers scrambling to figure out what is actually causing the pulsating pain sensation.  One theory is that it’s something neurological, not directly related to blood flow at all.

Sometimes the most obvious things about migraine are not so clear once we actually check them out.  As you can imagine, the re-thinking of something simple like pulsating pain could have (and is having) huge repercussions when it comes to migraine treatment.

And in this case it’s not just migraine.  The same phenomenon has been found in other pain conditions, including other headache related conditions.

Not knowing something can actually be a benefit – as long as you know that you don’t know.

If you want to investigate this fascinating line of research further, check out:

Vasoconstrictor: Migraine Headaches

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For many years, a vasoconstrictor migraine headaches connection was at the heart of migraine research.  But recently we’ve learned a lot more.  It’s now much more common knowledge that migraine is much more than migraine headache (and sometimes there’s no headache at all).  We’ve also learned that migraine attacks are a web of reactions that do not just involve changes in the blood vessels.

As a matter of fact, we now know that both vasoconstriction and vasodilation may be a part of a migraine attack – or perhaps may not be involved at all.

Smart Pipes?

Vasoconstriction and vasodilation of course refer to blood vessels.  They constrict (get smaller) and dilate (get larger) to control blood flow – you can think of them as pipes in your home, but “smart” pipes.

Back in the day we believed that migraine happened when blood vessels dilated – therefore we looked for medications that would constrict them.

Although some of these medications and treatments worked (somewhat), we now believe that many of them work for different reasons.  Triptans are a classic example – though they do have a vasoconstriction effect, researchers now believe that this is not why they relieve migraine symptoms.

In fact, today researchers are looking for drugs that are not vasoconstrictors.  Why?  Because of concerns that constricting the blood vessels will lead to more heart attacks and strokes.

Some heart problems have been reported by people taking drugs such as triptans.  On the other hand, some studies have suggested that there’s generally no connection.

Many doctors are reluctant to prescribe triptans or other vasoconstrictors to patients who are at a high risk of heart disease.  And there is evidence that migraineurs in general are at a higher risk than the general population.

On of the drugs being researched is Lasmiditan, which is not a triptan but a ditan.  Like triptans, it would be taken for a specific migraine attack, but without the potential dangers of vasoconstrictors.

We can hope that more and more treatments will be available that can stop a migraine attack without unnecessary side effects and dangers.  Meanwhile, specialists are increasingly cautious about prescribing too many vasoconstrictors for migraine when there are other options.

Ice Cream Headache (Brain Freeze!): A New Study

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Although the famous ice cream headache (also known as brain freeze, or more officially headache attributed to ingestion or inhalation of a cold stimulus) was first studied seriously almost 45 years ago, it’s still somewhat of a mystery.  But a new study in the USA may be giving us clues not only about ice cream headache, but about other types of headaches as well.

British neurologist Dr. R. O. Smith, began studying brain freeze in 1968.  Since then, there are several interesting facts that have come to light.  For example:

  • Brain freeze seems to be more of a problem in warmer climates
  • It doesn’t seem that any permanent damage is done
  • Nerves in the roof of your mouth seem to trigger changes in blood vessels, triggering the pain
  • Migraine patients seem to be more susceptible
  • An ice cream headache can trigger a migraine attack in migraine patients
Brain freeze - ice cream headache
Photo courtesy of Tom Newby Photography

The new study, entitled Cerebral Vascular Blood Flow Changes During ‘Brain Freeze’, confirms the blood vessel theory.

So what seems to be happening?  First, typically, something cold comes into contact with the roof of your mouth.  Quickly, blood vessels dilate (get bigger around), allowing for more blood flow.  In particular, the anterior cerebral artery seemed to react.  This may be a response to ensure that the brain stays warm.

Researchers believe that pain may occur at this point because of the sudden rise in pressure from the increased blood flow.

Soon after, the blood vessel constricts, presumably to keep the blood flow from getting to high.  At this point, the patient’s pain recedes.

This type of headache is an interesting one to study – because it’s easier than most to study in the lab.  You can’t usually sit around waiting for a migraine attack to start, but a brain freeze is easy to trigger.  Because researchers believe that these types of headaches may have a lot in common with migraine headaches and post-traumatic headaches, for example, studies like this may provide clues to help us treat those as well.

For more, read this summary from the American Physiological Association: Changes in Brain’s Blood Flow Could Cause ‘Brain Freeze’.  For more general information about the causes and treatments of brain freeze, see Stop the pain of ice cream headache!

My head feels hot, swollen, and it HURTS – why?!

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What exactly is causing that migraine headache?  Yes, we know that headache is only one possible symptom of migraine.  Not everyone with a migraine attack has a headache.  But let’s face it, the headache is a common symptom.  But why does it happen in the first place?

The headache is a part of the chain reaction that happens during a migraine attack.  Long into an attack, messages start to be sent in earnest to nerves in the head and blood vessels from the brain, and back to the brain again.

So long before most people feel pain, the "migraine attack" has already been happening for quite some time.

Once doctors believed that changes in blood vessels were actually the cause of migraine.  Few believe that today – although there is a lot of discussion about just how blood vessels fit into the chain reaction of migraine.

However, at various points in a migraine attack, blood vessels do (usually) get larger and smaller (vasodilation and vasoconstriction).  (Note: vasodilation does not always occur in a migraine attack)

When vasodilation occurs in an attack, what typically happens?

  • Vasodilation:  Blood vessels are like "smart pipes" that control blood flow in the body.  So when vasodilation occurs, the blood vessels grow larger and allow more blood to flow.  And what typically happens with increased blood flow?  The area becomes warm and perhaps even red.  The blood flow may feel "over the top" – the pressure will increase and begin to feel uncomfortable.
  • Vascular permeability:  Another thing that happens is that spaces appear in the walls of the blood vessels, allowing some materials to pass through.  Blood plasma, the material that carries blood cells, leaks through.  Now there is an increase in fluid in the area, causing more of a feeling of pressure and swelling.  When there is an injury such as a cut, this allows materials to enter the area which can help fight invading bacteria.  In an autoimmune disease, this inflammation can be triggered when it’s not needed.  Some of these materials can also increase the sensitivity to pain in the area.
  • Pain:  Pain can be caused by a complex web of things when it comes to migraine.  But carrying on with the theme of inflammation, the pressure against nerves and stimulation of nerves is a part of the pain process.  Swelling can also cause problems in muscles and joints, making it hard and/or painful to move properly.  Loss of function can also simply be a result of pain.

Because the causes of pain are complex, it’s wise to talk to a doctor familiar with migraine about your treatment, instead of relying on over the counter "anti-inflammatories", which, when misused, can make the problem worse.  However, inflammation is a major player in the causes of migraine headache.

Check here for more on terminology and the causes of migraine headache.

Birmingham City University has a helpful page on inflammation.  Although it is more specifically about inflammation in injuries, it’s a helpful overview.

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The articles on Headache and Migraine News are © 2004-2024 J. Cottrill.
Every effort is made to ensure the accuracy of each article, and to point you to further sources of information. However, this site is for informational purposes only and should never replace a visit to your doctor.