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Modeling Migraines

I told, in brief, the story of the first migraine I ever had on this blog a little while back:

“Years and years ago (around 1994), I was sitting on my bed playing Aladdin for the Sega Genesis when I noticed I was having trouble seeing the screen. It was like a blind spot near the middle of my visual field, a distortion or void that my mind tried ineffectually to fill in with nearby colors.

I was experiencing my very first visual aura — [a blind spot in the middle of your field of vision, and] a precursor to my very first migraine.”

That was about 23 years ago, when I was seven or eight. I’m 31 now, and don’t let the brevity of my retelling fool you: I can recall the entire story with near-perfect clarity. Perhaps if that had been one of the few migraines I ever received, I wouldn’t remember it quite so well. That’s not the way it worked out, though, and so what might have once been lost to the recesses of my memory was instead burned into it as the opening salvo of what has thus far been a lifelong battle with an invisible, occasionally annoying, occasionally devastating foe.

For all I’ve cursed them over the years, I still find migraines kind of fascinating. They impact a significant chunk of the population — about 12 percent — but they remain a topic about which we simultaneously know plenty and not enough. To try and learn more about migraines is to understand that there’s only so much you can truly know about migraines right now. There are still questions waiting to be answered about exactly how and why migraines are generated: What are these things? Why are they so difficult to treat? Why are they different for everybody?

Research is ongoing, though, and several different models are helping physicians shed new light on what makes migraines tick — which could, in turn, lead to new and more effective treatment options down the line.

 “There’s a lot of research going into this,” said Swathi Vijayaraghavan, MD, an assistant professor of Clinical Neurology, noting that the most prevalent model right now focuses on something called cortical spreading depression.

“That’s a concept wherein there is essentially a wave of depolarization across the outer layer of the brain that is thought to do multiple things which generates migraines,” she added. “This is felt to be the cause of auras. The spreading depression also causes changes in the blood brain barrier which causes an inflammation in the meninges, a layer of tissue surrounding the brain that is pain sensitive and causes the head pain.”

In the cortical spreading depression model, things typically kick off at the very back of the brain, in or around the occipital lobe — where vision is processed. This is why migraineurs who experience visual aura tend to do so right before the headache itself gets rolling. It’s also why the visual aura can take so many forms, such as rips, distortions, or glowing spots.

According to Vijayaraghavan, another model involves the brain’s trigeminovascular system, wherein the neurons in the trigeminal ganglion and upper cervical dorsal roots — which help apply innervation to the blood vessels in the head and covering around the brain — are activated.  Signals from these neurons project to the trigeminal nucleus caudalis, an area in the brainstem that is responsible for projecting to different spots higher up in the brain important for perception of and response to pain. Activation of the various pathways to, from and within the system, Vijayaraghavan said, could generate pain associated with migraines.

It’s by working within this model that researchers are making progress toward medications that specifically target migraines where they originate.

“Right now the hot migraine research in neurology has to do with the calcitonin gene-related peptide, which is something we know is released by these trigeminal ganglion nerves,” Vijayaraghavan said. “This has been leading to targeted therapies or antibody-mediated therapies to address that particular peptide.”

“The fact that we’re at the point of making monoclonal antibodies for this is pretty awesome,” she added. “It might be a little bit away, but it’s still exciting because it’s different from all the medications we’re currently using.”

Next month: Okay, so we know more about what makes migraines tick — but what do we do about them? In the second part of this piece, we look at the complicated practice of medicating for migraines.

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