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vasoconstriction

Whatever Happened to Lasmiditan?

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We last talked about Lasmiditan in 2012, with hopes that it would be on the market by now. But although a lot of money is being invested, and trials are still ongoing, it’s not likely we’ll see Lasmiditan for migraine until 2018 or later.
CoLucid
Lasmiditan is a migraine abortive and a serotonin receptor agonist, like triptans. But unlike triptans, it doesn’t seem to cause vasoconstriction – very important for those at risk of stroke and heart disease.

Lasmiditan is going to undergo phase III trials, further investigating the drugs ability to fight headache, nausea, photophobia and phonophobia. The company, CoLucid Pharmaceuticals, also has permission from the FDA to include some patients who have some cardiovascular risk factors.

Another future trial will be a pediatric study.

Lasmiditan remains a very promising migraine drug, which may be a major alternative to the familiar triptan medications. But we’ll probably be waiting until 2018 before most of us will have a chance to use it.

Read more about the development plan for Lasmiditan here.

For more, see Emerging therapeutic options for acute migraine: focus on the potential of lasmiditan

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!

Vasodilation and Migraine – The fall of a theory

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Blood vessels have sometimes been described as "smart pipes".  Not only does blood move through them, they are also involved directly in controlling the rate of flow.  They can get bigger and smaller, processes known as vasodilation and vasoconstriction.

Once upon a time, migraine was known as a "vascular" disorder.  In fact, some form of this theory has been around for 350 years.

Migraine and Vasodilation in The Lewiston Daily Sun 1974
The Lewiston Daily Sun, May 1974

The idea was that the dilation of blood vessels directly led to the pain of migraine.  And so, some treatments focused on constricting the blood vessels.

There were various clues that led researchers to buy into the theory.  For example, ergotamine treatments also seemed to constrict the blood vessels, as it calmed the migraine attack.  And, in fact, the very popular Triptan drugs were developed as vasoconstrictors!  Now we believe that they work for a totally different reason.

But in recent years, the vasodilation theory has been falling apart.

First, we discovered that the migraine process was much more complex.  Though vasodilation may happen, there’s much more to a migraine attack than just changes in the blood vessels.

So vasodilation is not the key element of migraine.  It’s not enough to explain migraine symptoms.

Not only is this not a sufficient cause, we now know it’s not even necessary.

Migraineur advocate Teri Robert, reporting on a presentation of the American Headache Society in November, summed it up this way – Vasodilation may occur as part of the disorder, but is not required for Migraine pain.  (Read Vasodilation Not Necessary for Migraine)

In other words, vasodilation may not happen at all in a migraine attack!

That doesn’t mean it doesn’t happen commonly, simply that it’s not required.  It may often still be a part of the process, but it’s not they key aspect, and certainly not the cause of all migraine pain.

The report at the AHS meeting, presented by Dr. Andrew Charles, also pointed out that some drugs that cause vasodilation do not cause migraine attacks.

What does this mean for the patient?

  1. We can now know that information claiming migraine is a "vascular disorder" caused by vasodilation of the blood vessels is out-dated.
  2. We can give a lower priority to treatments that claim to stop migraine by vasoconstriction.
  3. We don’t need to be afraid of medication just because it may cause vasoconstriction.
  4. We can be glad that the medical community is being freed from this erroneous idea.  This is actually opening the doors to new treatments that focus on other more foundational aspects of migraine.

Further reading: The vascular theory of migraine—a great story wrecked by the facts

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The articles on Headache and Migraine News are © 2004-2024 J. Cottrill.
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