Speaker 1: My name is Kaylee. I've been getting migraine since I
Speaker 1: was a kid, but over the last eight years or
Speaker 1: so it's become a battle against chronic daily migraines. The
Speaker 1: singular worst pain I've ever felt in my life. I
Speaker 1: will never forget it. It was January twenty nineteen, at
Speaker 1: three am, during a blizzard. I woke up with a
Speaker 1: ten out of ten pinscale migraine, which is the kind
Speaker 1: where you worry that maybe this time it's actually something
Speaker 1: more serious, like a stroke or a meningitis. Takes a
Speaker 1: lot to get me out of my bed, to drive
Speaker 1: myself to the hospital during a snowstorm, to get an
Speaker 1: IV shoved in my arm. Hopefully that gives some indication
Speaker 1: of how miserable these things are. They're not just headaches.
Speaker 1: For every day that I have actual migraine pain, there's
Speaker 1: a period afterwards of what I call the migraine hangover,
Speaker 1: where you're just completely drained and foggy, and the nausea
Speaker 1: can be horrific. And I get really sensitive to smells,
Speaker 1: both as a trigger and in terms of getting phantom
Speaker 1: smells before a migraine hits, which is bizarre. It could
Speaker 1: be a totally debilitating thing, and it could be really
Speaker 1: hard to feel like you're being taken seriously because it's invisible.
Speaker 1: It's incredibly frustrating to have to cancel plans or call
Speaker 1: off work because you have another migraine. But sometimes over
Speaker 1: the counters or even your prescription migraine medicine just still
Speaker 1: isn't enough to make you functional enough to go about
Speaker 1: your day.
Speaker 2: I'm Katie, and I have chronic migraine. Chronic is defined
Speaker 2: as fifteen or more days a month with migraine symptoms.
Speaker 2: I average about twenty eight days a month. I've had
Speaker 2: migraine pretty much my entire life. My mom also has migraine.
Speaker 2: So when I was five or six years old and
Speaker 2: started getting excruciating headaches so bad I threw up, my
Speaker 2: parents knew what was going on. At the time, there
Speaker 2: weren't a lot of migraine drugs available, and especially not
Speaker 2: for young kids, so it was just over the counter painkillers,
Speaker 2: a caffeated drink, and a nap. Over the years, I
Speaker 2: also started having abdominal migraine like regular migraine, but the
Speaker 2: pain was mostly in my stomach. In high school, I
Speaker 2: occasionally had vestibular migraine, where the primary symptom is intense
Speaker 2: nausea and dizziness without much head pain, and.
Speaker 3: Which could last for months at a time.
Speaker 2: I carried on having a few migraine episodes a month
Speaker 2: through college, when I got sumatripton, an older.
Speaker 3: Aboard of drug, which worked for a while.
Speaker 2: Still about once a year nothing would work and I'd
Speaker 2: have to go to the er for an IV cocktail.
Speaker 2: Then in my mid twenties, the medication stopped working as well.
Speaker 2: The episodes became a lot more frequent, until they were chronic,
Speaker 2: and they'd been that way for about three years. In
Speaker 2: that time, I've tried most treatment options, some of which
Speaker 2: didn't work at all and some of which had side
Speaker 2: effects I couldn't tolerate.
Speaker 3: Right now, I've landed on one anti.
Speaker 2: Epileptic drug that helps I get an IV infusion of
Speaker 2: monoclinal antibodies once every three months, and I'd take a
Speaker 2: pill nightly and then another pill when I'm getting a migraine.
Speaker 2: Even though they don't completely treat my migraine. Drugs are
Speaker 2: huge for my quality of life, but they're also really expensive,
Speaker 2: so I spend a lot of time on the phone
Speaker 2: with insurance. I also use an neerrosimulation device and my
Speaker 2: trigeminal nerve to try to prevent and manage migraine. I've
Speaker 2: a hat made of ice packs to help with head pain.
Speaker 2: I see a therapist who specializes in chronic illness. I
Speaker 2: stay extremely well hydrated. I never leave home without sunglasses,
Speaker 2: and I try to be realistic when I'm feeling especially
Speaker 2: bad and take it easy, which is sometimes easier said
Speaker 2: than done.
Speaker 4: The first sign that a migraine is brewing is that
Speaker 4: my eyes start it's behaving. I get my migraine solely
Speaker 4: on the right side of my head, and things just
Speaker 4: look brighter out of that eye. It feels like that
Speaker 4: eye is open wider than the other, even though it isn't.
Speaker 4: I'll have flashing lights and sometimes it's hard to find words.
Speaker 4: Sometimes I can avoid getting a full on migraine if
Speaker 4: at that particular instent, I take a CGRP inhibit or
Speaker 4: rescue medication, eat a candy bar, and drink a diet soda.
Speaker 4: If not, the pain starts in the top back part
Speaker 4: of my head. There was a migraine commercial a long
Speaker 4: time ago that showed lightning bolts radiating out of a
Speaker 4: spot on the woman's head, and that's what it feels like. Lights, sound, smells,
Speaker 4: and heat become painful. My cheek feels like something is
Speaker 4: pressing inward. Sometimes, if it's bad enough, my jaw and
Speaker 4: teeth start hurting and the pain begins to radiate down
Speaker 4: my back. At this point, pretty much all is lost
Speaker 4: and I have to go lie down. Strangely, it helps
Speaker 4: to lie down on my right side and press the
Speaker 4: painful part into the pillow. It may be the cool
Speaker 4: pillow or the pressure, but if I can get to sleep,
Speaker 4: I'll generally be better the next day.
Speaker 5: My name is Darcy. I'm twenty eight, and I started
Speaker 5: having migraines when I was around ten years old. I've
Speaker 5: been diagnosed with chronic migraines, but I also have atypical
Speaker 5: migraines occasionally. So when I was nineteen, I woke up
Speaker 5: one morning and the right side of my face and
Speaker 5: my right arm felt a little tingly. The more I
Speaker 5: moved around, the worse the tingling got to the point
Speaker 5: where the right side of my body was just starting
Speaker 5: to feel numb. We let a couple hours pass, I think,
Speaker 5: and nothing was changing. So at this point my parents
Speaker 5: were starting to feel pretty concerned. Because when you think
Speaker 5: about someone with symptoms of having one side of their
Speaker 5: body be numb, you think about someone having a stroke.
Speaker 5: So we go to the hospital and one thing I'll
Speaker 5: never forget about this day is when we got there,
Speaker 5: they needed me to sign some sort of paperwork and
Speaker 5: I couldn't do it. My hand was so numb that
Speaker 5: I couldn't hold a pen properly. They did all of
Speaker 5: the tests that you would do for a stroke, all
Speaker 5: of which came back completely normal. After the test, doctor
Speaker 5: came in and he asked me, do you have migraines?
Speaker 5: And I said yes, And he said, I think what
Speaker 5: you're experiencing is in a typical migraine, which I had
Speaker 5: never heard of before. But he explained to me that
Speaker 5: they can come in all different shapes and sizes, but
Speaker 5: some of the more common types present as stroke symptoms.
Speaker 5: It took about two weeks for the numbness to completely
Speaker 5: fade away, but even now, almost ten years later, I
Speaker 5: still have a small spot above my right eye that
Speaker 5: just doesn't feel quite right. But that's my atypical migraine story.
Speaker 5: Definitely one of the scarier days of my life. But
Speaker 5: I am grateful because I know what it feels like
Speaker 5: in case it happens again.
Speaker 6: Hi, my name is I'm thirty five years old and
Speaker 6: I've been having migraines since I was about twelve. These
Speaker 6: progressed to having about fifteen to twenty headache days per month.
Speaker 6: I had a lot of anxiety around my triggers, such
Speaker 6: as flying in airplanes, weather changes, too much sun or heat,
Speaker 6: certain foods, and fluorescent lighting. I'm a veterinarian, so I
Speaker 6: went through a lot of schooling, and school could sometimes
Speaker 6: be difficult since the migraines caused me a lot of
Speaker 6: pain and to lose concentration. I was taking over the
Speaker 6: counter pain medications almost every day, and I worried about
Speaker 6: long term damage to my organs. I tried everything from
Speaker 6: diagnostics such as MRI supplements, preventive medications, and glasses that
Speaker 6: would reduce the blue light from the fluorescent lighting. And
Speaker 6: thankfully this all changed about two years ago when my
Speaker 6: neurologists prescribed the new monocludal antibodies, the CGRP inhibitors. I
Speaker 6: have the monthly injection for prevention and an oral abhorre
Speaker 6: and this has absolutely improved the quality of my life
Speaker 6: and reduce the severity and frequency of my migraines.
Speaker 1: Right.
Speaker 7: My name is Chris. I'm a twenty six year old
Speaker 7: transgender man, and I've been dealing with migraines for most
Speaker 7: of my life. It all really started rolling when I
Speaker 7: was in middle school, so around twelve years old, and
Speaker 7: I started having weekly, if not multiple times a week
Speaker 7: abouts of what I thought at the time was food poisoning.
Speaker 7: My head would hurt like there was someone blowing up
Speaker 7: a balloon inside it and there was just no space
Speaker 7: for anything to go, and the light would hurt my eyes.
Speaker 7: I would get incredibly dizzy, nauseous, and I would have
Speaker 7: to excuse myself, go to the bathroom, throw up, and
Speaker 7: return to class because that was really the only option
Speaker 7: I had. This kind of just continued for years and years.
Speaker 7: I never really had a chance to get things checked
Speaker 7: out until god, now, fourteen years later, now that I
Speaker 7: am an adult working in the healthcare system, I have
Speaker 7: decent insurance. So over the past twelve months, I have
Speaker 7: had two MRIs that showed absolutely nothing out of the ordinary.
Speaker 7: It's hard to stay hopeful in terms of treatment and possibilities,
Speaker 7: especially considering that we have no idea where this comes from.
Speaker 7: I almost was hoping that we would discover a freak
Speaker 7: brain tumor or something like that, because that would mean
Speaker 7: a real answer. It's always an interesting concept to grapple
Speaker 7: with knowing that this is something that is so incredibly
Speaker 7: common and we just have so few answers as to
Speaker 7: why so many people deal with this. But it is
Speaker 7: something that I know there is a lot of research
Speaker 7: happening with and despite having a very rocky history, I
Speaker 7: do remain hopeful.
Speaker 3: Overall, Thank you everyone who shared your story with us.
Speaker 3: We really appreciate it, We really do.
Speaker 8: Yeah, thank you for taking the time to write to
Speaker 8: us and to share your story with us and with everyone.
Speaker 8: It's yeah, thank you.
Speaker 3: Hi. I'm Aaron Welsh and I'm Aaron Allman Updyke and
Speaker 3: this is this podcast will Kill You And today we're
Speaker 3: talking migrain. Yeah. What a topic? Erin what a topic.
Speaker 3: I feel like I recently said something about, oh, this
Speaker 3: is the most requested topic, and I was wrong because
Speaker 3: it's got to be migrain, right.
Speaker 8: I think it's definitely it's up there.
Speaker 3: It's over there. Yeah, And so I really sort of
Speaker 3: feel like this has been a a long time coming.
Speaker 3: But b I still feel weirdly unprepared despite how much
Speaker 3: reading I know that we've both done on this.
Speaker 8: Same I like always feel unprepared. Yeah okay, and when
Speaker 8: it comes to brain stuff, I feel like an extra
Speaker 8: layer of unprepared. But today it's still going to be
Speaker 8: a great episode promise.
Speaker 3: Oh yeah for sure. And I feel like listeners of
Speaker 3: the podcast have gotten used to sitting with the unknowability
Speaker 3: of certain things AKA great question, I don't know.
Speaker 8: I think that's one of my favorite parts about our podcast.
Speaker 3: On Me Too, Me Too. Another favorite part of our
Speaker 3: podcast is guess what quarantine ay time?
Speaker 1: What?
Speaker 3: Absolutely so, what are we drinking this week? This week
Speaker 3: we're drinking the hammer Head because migraines are debilitatingly painful
Speaker 3: and it feels like a hammer in your head, in
Speaker 3: your head? Ow yep.
Speaker 8: What's in the Hammerhead?
Speaker 3: In the Hammerhead is essentially like a boozy aphagatoy so good.
Speaker 3: It's got espresso, which you can do decaffeinated if you
Speaker 3: would like. It's got ice cream naturally, it's got bourbon,
Speaker 3: and it's got a little bit of amaretto yum.
Speaker 8: We'll post the full recipe for that quarantini as well
Speaker 8: as our non alcoholic plasy burrita on our website This
Speaker 8: Podcast will kill You dot com and on our social
Speaker 8: media channels of course.
Speaker 3: Of course, on our website This Podcast will kill You
Speaker 3: dot Com you can find all sorts of cool things.
Speaker 1: You know.
Speaker 3: We've got transcripts, We've got links to merch to bookshop
Speaker 3: dot org, affiliate account, to our Goodreads list, to music
Speaker 3: by Bloodmobile, to our Patreon. You can find the sources
Speaker 3: for each and every one of our episodes. There's probably
Speaker 3: more stuff. How do we not have this down by now?
Speaker 8: Oh? I thought you did a phenomenal job.
Speaker 3: Thank you, thank you. I try.
Speaker 8: Well with that. Shall we get into the biology of migraine?
Speaker 3: Yes? Please?
Speaker 8: All right, we'll take a quick break and get to it.
Speaker 8: So what even is a migraine?
Speaker 3: That sounds like a great place to start. That's where
Speaker 3: we're going to start.
Speaker 8: I'm going to start with a quoted definition which happens
Speaker 8: to be from a pretty old paper, but the definition holds,
Speaker 8: so we'll start there. This is from a New England
Speaker 8: Journal of Medicine article from like two thousand and two,
Speaker 8: which says, quote, Migraine is a common chronic in pacitating
Speaker 8: neurovascular disorder, characterized by attacks of severe headache, autonomic nervous
Speaker 8: system dysfunction, and in some patients, an aura involving neurologic
Speaker 8: symptoms unquote. Biology section over, that's our definition. So that's
Speaker 8: the jargoned version. The way that I'm going to break
Speaker 8: down this biology section is to try and give you
Speaker 8: an idea of what migraine really is and as much
Speaker 8: as we can know about what's happening during these migraine attacks.
Speaker 8: So migraine attack can be divided into three to four
Speaker 8: main parts or kind of like sections, and then there's
Speaker 8: intermigraine intervals, like between migraines. So first we'll go over
Speaker 8: what these parts are, what these phases of a migraine
Speaker 8: attack are, what they look like, what they feel like,
Speaker 8: which you heard a lot of in our first hand accounts.
Speaker 8: And then we'll go over what we know so far
Speaker 8: about what's happening in our brains during these attacks. But forewarning,
Speaker 8: as will come as a surprise to no one listening
Speaker 8: to this episode if you've ever listened to TPWKY before,
Speaker 8: there's a lot that we don't know, but there is
Speaker 8: some stuff that we do know, and so I'll try
Speaker 8: to get into some of the nitty gritty of that
Speaker 8: as well. So a migraine attack generally starts with a
Speaker 8: period of prodromal symptoms. This period is often called the
Speaker 8: premonitory symptoms period, which can start anywhere from two hours
Speaker 8: to two days prior to the actual headache that most
Speaker 8: of us associate with migraine. So these symptoms can rain
Speaker 8: from anything like fatigue or yawning or impaired concentration. You
Speaker 8: could have neck pain or stiffness, water retention, nausea, photophobia
Speaker 8: which is difficulty looking at light. You might have food cravings.
Speaker 8: It's a really long and kind of diverse list of
Speaker 8: symptoms that someone could have for up to two days
Speaker 8: a day or two before the migraine attack itself. About
Speaker 8: eighty percent of people that get migraines have some kind
Speaker 8: of these prodrumal symptoms, and then for about thirty percent
Speaker 8: of people with migraines, the next phase is an aura.
Speaker 8: And a lot of people have probably heard of an aura,
Speaker 8: but an aura are these very bizarre, transient focal neurologic
Speaker 8: symptoms of various kinds. Most often, like ninety percent of
Speaker 8: the time, it's these visual symptoms. The most common one
Speaker 8: is called a scatoma or a scintillating scatoma, which sounds
Speaker 8: fancy but in fact is terrifying having had these episodes.
Speaker 8: It starts as like a flickering spot, a flickering kind
Speaker 8: of light spot, either in one eye or in both eyes,
Speaker 8: and then this spot can kind of grow or move
Speaker 8: or change and keep flickering, and scatoma just means like
Speaker 8: a blind spot. So wherever you see this flickering wave
Speaker 8: or curve of light, you can't really see anything except
Speaker 8: that light, but the vision around it usually remains the same,
Speaker 8: and this might expand, or people can see different kinds
Speaker 8: of patterns, like a crescent or a zigzag, or different shapes,
Speaker 8: and then eventually it just stops. But an aura isn't
Speaker 8: only visual. That's one type of aura. People can also have,
Speaker 8: like paresthesias, so like feeling tingling or prickling sensations, usually
Speaker 8: just in one part of the body, or it could
Speaker 8: be like a numbness of the face or your arm.
Speaker 8: It could even be things like difficulties with expressive language,
Speaker 8: not being able to find your words, or not being
Speaker 8: able to say words the way that you could just
Speaker 8: minutes prior, and even more rarely, an aura could be
Speaker 8: some kind of motor dysfunction, like all of a sudden
Speaker 8: not being able to use your hands or your legs.
Speaker 8: A lot of this might sound a lot like a stroke,
Speaker 8: because some of these symptoms can really mimic that. So
Speaker 8: this aura phase usually starts anywhere from five minutes to
Speaker 8: an hour prior to the onset of the headache, and
Speaker 8: it usually lasts under an hour and is followed pretty
Speaker 8: immediately by the headache part of migraine. That's the part
Speaker 8: that people think of when they think of migraine most often.
Speaker 8: So let's get to that. What is a migraine headache itself?
Speaker 8: Aka how do we define a migraine headache versus any
Speaker 8: other kind of headache? So, first, this is a headache
Speaker 8: that most often is unilateral. It's on one side of
Speaker 8: the head, or it at least starts off on one
Speaker 8: side of the head and then it might move to
Speaker 8: the rest of the head. It's usually described or characterized
Speaker 8: like a throbbing pain or like a pounding pain rather
Speaker 8: than a tension type pain. And in general, a migraine
Speaker 8: is classified as moderate to severe intensity, like the pain
Speaker 8: is bad enough that you can't get out of bed,
Speaker 8: you feel like you need to just lay down. And
Speaker 8: that's also in part because the pain generally increases with activity,
Speaker 8: which essentially forces you to just lie down. So those
Speaker 8: four characteristics unilateral throbbing pain, moderate to severe intensity, and
Speaker 8: increasing with activity. Based on the International Classification of Headache Disorders,
Speaker 8: which is like the criteria that are used to diagnose migraine,
Speaker 8: a migraine has at least two of those four criteria, Okay,
Speaker 8: And on top of that, migraine has either nausea and
Speaker 8: vomiting and or photophobia or phonophobia, so like severe light
Speaker 8: or sound sensitivity. I know your faces, it sounds.
Speaker 3: I mean like I know many people that have migraines.
Speaker 3: My mom, my grandma had horrible migraines her whole life.
Speaker 3: And I think it's just when you lay out all
Speaker 3: of the things that you can experience, it's just horrific,
Speaker 3: it really is.
Speaker 8: And here's an even more horrific part. The duration. Yeah,
Speaker 8: by definition, a migraine is also a headache that's lasting
Speaker 8: between four and seventy two hours. I'm gonna say that again.
Speaker 8: This is a severe headache with nausea or photophobia, not
Speaker 8: being able to look at light that increases with activity
Speaker 8: that's throbbing in your brain for four hours at a minimum,
Speaker 8: or two hours if you're a kid, and it can
Speaker 8: last up to three days. Meaning you go to bed
Speaker 8: with a headache and you wake up with the same headache,
Speaker 8: and a migraine isn't even over when it's over, because
Speaker 8: the fourth phase of migraine is the post dromal phase,
Speaker 8: and this can last again another one to two days
Speaker 8: after the headache subsides. This recovery phase can have increased
Speaker 8: in tiredness or somnolence. It can have difficulties in concentration.
Speaker 8: A migraine altogether is a phenomenon that affects the brain
Speaker 8: on a pretty large scale, and the full duration of
Speaker 8: a migraine attack can last up to seven days if
Speaker 8: you include the premonitory and the recovery symptoms as well
Speaker 8: as the headache itself.
Speaker 3: I've heard it described as a symphony in four movements,
Speaker 3: but I feel like that's way, way too pleasant language
Speaker 3: to describe what's happening.
Speaker 8: I agree, it founds like a symphony is like nice,
Speaker 8: this is it's a cacophony in four movements.
Speaker 3: Yeah, yeah, yeah, my gosh, I know.
Speaker 8: And that's that's kind of that's just how we define
Speaker 8: the migraine. So, of course, then knowing all of this,
Speaker 8: knowing how debilitating a migraine can be, how severe it
Speaker 8: can be, the question or questions are like, why does
Speaker 8: this happen? How does this happen? Who does this happen to?
Speaker 8: How can we stop this and never have this again?
Speaker 8: As promised, I do not have.
Speaker 3: All those answers, but you have some of them.
Speaker 8: I sure do. So here is what we do know,
Speaker 8: or at least what the consensus so far is about
Speaker 8: what we think is going on in the brain with
Speaker 8: a migraine. So what we know so far is that
Speaker 8: a migraine headache depends on the activation of a pathway
Speaker 8: in our brain called the trigemino vascular pain pathway, and
Speaker 8: it very likely involves a little peptide called CGRP or
Speaker 8: calcitonin gene related peptide. This is a neuropeptide. We'll talk
Speaker 8: about it in a little bit more detail. But let's
Speaker 8: define some of these things, shall we.
Speaker 3: Yeah, So the trigeminal.
Speaker 8: Nerve you may have heard of, This is cranial nerve
Speaker 8: number five. So this is one of our twelve cranial
Speaker 8: nerves that is responsible for all of the sensation to
Speaker 8: our face pretty much, and also innervates muscles that are
Speaker 8: involved in chewing and biting. So this is a predominantly
Speaker 8: sensory nerve. It's mostly carrying information from the face to
Speaker 8: the brain and then from part of our brain stem
Speaker 8: into the cortex of our brain. And then there are
Speaker 8: some nerves that are also involved with muscles and so
Speaker 8: are more efferent, sending signals for muscle contraction. Right, So,
Speaker 8: this trigeminal nerve mostly sensory, and like many nerves, most nerves,
Speaker 8: is very interrelated with vasculature. It forms like complexes of
Speaker 8: nerves and arteries and veins, and in the case of
Speaker 8: the trigeminal nerve, its projections, especially in our brain, are
Speaker 8: very strongly associated with the vasculature in our brain and
Speaker 8: our ninges that's the covering of our brain spinal cord,
Speaker 8: both the dura mater, which is the outer layer of ourminingis,
Speaker 8: and the pia mater, which is the innermost layer of
Speaker 8: our meaningis. So this trigeminal complex, as it's called, has
Speaker 8: these a sending nerve axons that project into a whole
Speaker 8: bunch of brain regions in our brainstem our, hypothalmus, our thalmis,
Speaker 8: our cortex. All of these regions of our brain are
Speaker 8: involved in a whole bunch of stuff that we happen
Speaker 8: to see dysregulated during a migraine. These involve our response
Speaker 8: to pain and no suception. So no susception is just
Speaker 8: the actual nerve signals of pain, like our nervous system
Speaker 8: getting those signals is the process called no susception. Our
Speaker 8: no susceptors are pain nerve fibers. There are a bunch
Speaker 8: of other neurons that are projecting to parts of our auditory, visual,
Speaker 8: and olfactory system, part of our cortical brain, regions that
Speaker 8: are involved with movement or even concentration. All of these
Speaker 8: different brain regions that happen to correspond to a lot
Speaker 8: of the non pain symptoms of migraine as well as
Speaker 8: these no susceptive or pain related symptoms. So think things
Speaker 8: like photophobia, nausea, vomiting, difficulty focusing, all of that. So
Speaker 8: we know that the trigeminal vascular complex is activated and
Speaker 8: involved in this process of migraine and in kind of
Speaker 8: all of the phases of it.
Speaker 3: But why aarin.
Speaker 8: Have I ever answered a why question on this podcast.
Speaker 3: Actually, I'm sure that you have.
Speaker 8: Yes, I'm not going to right now. No, that's where
Speaker 8: I will get to the part where I go I
Speaker 8: don't know, but let me tell you more about what
Speaker 8: we do know, all right. So we know that it's
Speaker 8: the trigeminal vascular complex it's activated. We also know that
Speaker 8: this specific peptide, CGRP calcitonin gene related peptide is very
Speaker 8: involved in this process. This is a peptide that we
Speaker 8: see released by this trigeminovascular complex during migraines. And we
Speaker 8: now know that blockade of this peptide or its receptors
Speaker 8: by various medications is effective in many cases at stopping migraine.
Speaker 8: We think that CGRP acts predominantly in the dura mater,
Speaker 8: so the outer layer of our menins, and that what
Speaker 8: it does is modulate the trafficking of these no susceptive signals.
Speaker 8: What does that mean. It means that CGRP is involved
Speaker 8: in the sending and receiving of the pain signals that
Speaker 8: are involved in migraine, and it may also be involved
Speaker 8: in inflammation. And there's still some thought that inflammation is
Speaker 8: involved in the migraine process.
Speaker 3: So if you're blocking that or stopping that neuropeptide through
Speaker 3: whatever medication, then it's like, okay, it can't be the
Speaker 3: messenger that causes all the pain, and that also then
Speaker 3: leads to inflammation exactly. And so in terms maybe this
Speaker 3: is you know, jumping ahead a little bit, but in
Speaker 3: terms of when you say stop a migraine, is that
Speaker 3: at what point can you stop a migraine? Is there
Speaker 3: like a threshold beyond which that like the point of
Speaker 3: no return?
Speaker 8: I guess it's a really good question. In general, all
Speaker 8: the medicines that we use for migraine, especially for like
Speaker 8: acute migraine attacks, work best the earlier that they're given,
Speaker 8: And part of that is because once this process starts rolling,
Speaker 8: and especially once the pain has really started to take hold,
Speaker 8: there's an additional process we think of like central sensitization.
Speaker 8: So there's a thought that like, once the pain signals
Speaker 8: have started to be sent, now our brain is acting
Speaker 8: a little bit on overdrive in response to those signals,
Speaker 8: and then yeah, you're right, that's a really hard ball
Speaker 8: to stop rolling essentially.
Speaker 3: Okay, So it's like, ah, that old pathway, like exactly,
Speaker 3: I know it well, and then and just speed down
Speaker 3: it and then pain goes up. Yeah. And the variation
Speaker 3: in how long a migraine can last, so like, let's
Speaker 3: say that you don't stop the neuropeptide in time, or
Speaker 3: you lived in a period before there were drugs that
Speaker 3: could do that, or you don't have access to drugs.
Speaker 3: Whatever is the variability and how long that migraine will
Speaker 3: last is just sort of like the half life of
Speaker 3: the neuropeptide in your brain.
Speaker 8: I mean, maybe, no, yes, who knows? The answer is
Speaker 8: that we have no idea because everything that I just
Speaker 8: told you is a lot of information. It's a level
Speaker 8: of understanding that we did not have, say, fifteen twenty
Speaker 8: years ago, But it's also not helpful at all when
Speaker 8: it comes to understanding the why or even how this
Speaker 8: trigeminovascular system is activated in people with migraine. To begin with,
Speaker 8: we don't understand the initiation of migraine pain. We don't
Speaker 8: understand why it stops eventually, why it lasts for as
Speaker 8: long as it does, why it can be so different
Speaker 8: both between individuals as well as in one individual throughout
Speaker 8: their lifetime. There is so much that we don't know
Speaker 8: it's really frustrating. It is, it is. And then there's aura.
Speaker 3: Oh gosh.
Speaker 8: Aura is very interesting. It happens in about thirty percent
Speaker 8: of people with migraine, so it's not the most common
Speaker 8: form of migraine, migraine with aura, and it can happen
Speaker 8: in absence of a migraine headache as well, but that's
Speaker 8: even more rare. And here again we know a little
Speaker 8: bit about the mechanisms, but so much remains unknown. Aura
Speaker 8: is thought to happen from a phenomenon called spreading depolarization
Speaker 8: or cortical spreading depression, depression depolarization, same thing. And so
Speaker 8: when we have an aura, the symptoms tend to start
Speaker 8: kind of small and they grow or kind of propagate
Speaker 8: rather slowly, especially compared to another rapid depolarization phenomenon that
Speaker 8: we've talked about on this podcast.
Speaker 3: A seizure, ah okay.
Speaker 8: And so it's thought that what's happening during this time
Speaker 8: is that starting from some focal point in the brain,
Speaker 8: there's this membrane depolarization, and that's what happens whenever a
Speaker 8: nerve is firing, like a signal is firing. But this
Speaker 8: is happening like all in this one area and then
Speaker 8: propagating along the cortex of the brain like dumb kind
Speaker 8: of yeah, And we have like MRI and PET scan
Speaker 8: studies that show additionally changes in blood flow like hyper
Speaker 8: perfusion followed by hypoperfusion, so like more blood flow and
Speaker 8: then all of a sudden less blood flow in regions
Speaker 8: of the brain that are corresponding to the symptoms of aura.
Speaker 8: And there's evidence that this cortical spreading depression, this depolarization
Speaker 8: can then trigger or activate the trigeminovascular system, but we
Speaker 8: still don't know what the susceptibility is for this cortical
Speaker 8: spreading depolarization or depression. And we also don't know why
Speaker 8: is it then that only thirty percent of people have
Speaker 8: AURA with their migraine, et cetera. There's there's like some oh,
Speaker 8: this is involved and it activates the system, and maybe
Speaker 8: that's the pathway to then migraine pain. But what about
Speaker 8: when you don't have an aura, Because people with migraine
Speaker 8: with aura can also still have migraines without aura, So
Speaker 8: it's complicated.
Speaker 3: Uh So I wrote down a few questions, okay, because
Speaker 3: I knew that I was going to forget them, and
Speaker 3: I feel so overwhelmed by questions. I'm like brimming right now, overflowing.
Speaker 8: I'll try.
Speaker 3: Okay, why is the pain typically on one half of
Speaker 3: your head?
Speaker 8: Great question. So our cranial nerves are all paired, which
Speaker 8: means that you have two sets of them, and then
Speaker 8: you have two sets of those ganglia or the nerve bodies,
Speaker 8: and then two sets of those like acending axons as well.
Speaker 8: So probably you're having activation of one of your trigeminovascular complexes,
Speaker 8: like on one half of your brain at a time. Okay,
Speaker 8: but like that, that's my best guess.
Speaker 3: Why eron, I just told you I don't know her Okay, Okay,
Speaker 3: I'll try, I'll try to stay away from the ys. Okay.
Speaker 3: Another question I had was about the mechanism of aura
Speaker 3: as far as we understand, So you discussed how visual
Speaker 3: aura is the most common. Are the mechanisms the same
Speaker 3: for the other types of aura?
Speaker 8: Great question. Yes, it's thought that in general the mechanism
Speaker 8: of aura is this cortical spreading depression, and what your
Speaker 8: symptoms are will depend on where that depolarization is happening
Speaker 8: in your brain.
Speaker 3: And we don't know how aura is or is not
Speaker 3: linked to migraine pain.
Speaker 8: Mechanistically, we know from animal studies that the process of
Speaker 8: this cortical spreading depolarization can lead to activation of that
Speaker 8: trigeminovascular complex. How exactly we don't know, but we do
Speaker 8: see that correlation there.
Speaker 3: Okay, one last question. Okay, So you mentioned early when
Speaker 3: you were describing the various symptoms that can be associated
Speaker 3: during the migraine pain, like the headache part of migraine,
Speaker 3: and you commented on how similar they are to stroke.
Speaker 3: Why how? Sorry? I said, why how?
Speaker 8: I don't have a lot of hows for you either, Aaron,
Speaker 8: So that is a it's kind of a can of
Speaker 8: worms question, and in part it's because it does get
Speaker 8: into associations that exist between migraine and other neurologic and
Speaker 8: psychiatric disorders, including stroke. I don't have an easy, good
Speaker 8: answer for like why can migraine symptoms, especially aura symptoms,
Speaker 8: mimic a stroke? But they can They also can mimic
Speaker 8: some forms of seizures or epilepsy. Yeah, so I want
Speaker 8: to go into a little bit more detail, not necessarily
Speaker 8: on this path of physiology, but on like the big
Speaker 8: picture of migraine and migraine biology. Everything that I went
Speaker 8: over and the criteria that are in the ICHD three.
Speaker 8: Those are all for migraine, like called classic migraine and
Speaker 8: migraine with aura. There is also a distinction between what's
Speaker 8: called episodic migraine and so called chronic migraine. But the
Speaker 8: term chronic migraine is confusing and like a crappy term
Speaker 8: because like, most people who have migraines have them chronically.
Speaker 8: But what chronic migraine actually means is that people have
Speaker 8: a very high frequency of migraines. Chronic migraine is classified
Speaker 8: as at least fifteen headache days per month.
Speaker 3: Oh my god.
Speaker 8: Yeah, that's half of a month, and at least eight
Speaker 8: of these headaches meet criteria for migraine. Some of them
Speaker 8: can be non migronists headaches. Up to five percent of
Speaker 8: people with migraine meet criteria for chronic migraine at some
Speaker 8: point in their like migraine lifespan, because migraines can also
Speaker 8: change over time. But there are other types of migraine
Speaker 8: as well that I'm not going to really get into
Speaker 8: detail on, but I just want to mention that they
Speaker 8: exist because they're important. There's abdominal migraine, which is much
Speaker 8: more common in kids, but can persist into adulthood. It's
Speaker 8: very similar in terms of all of the prodramal symptoms,
Speaker 8: but instead of headache pain, it's intense abdominal pain that
Speaker 8: lasts between two and seventy two hours. And it has
Speaker 8: very similar non pain symptoms nausea, vomiting, photophobia. All of
Speaker 8: this huh yeah, I have a great paper if you
Speaker 8: want to read more details about it. But there's a
Speaker 8: huge connection between the mind and the gut, and there's
Speaker 8: association between migraine, headache, and abdominal migraine. There's a lot there.
Speaker 8: Migraine is also in relatively large part genetic, About forty
Speaker 8: to sixty percent of expression of migraine is from genetic factors.
Speaker 8: But that being said, this is nowhere close to like
Speaker 8: a one gene one disease problem. There are thirty eight
Speaker 8: different low side so far that have been identified as
Speaker 8: increasing our susceptibility to migraines. But there are also a
Speaker 8: handful of monogenic migraine syndromes. These are a single gene
Speaker 8: mutation that also leads to migraine, and these, while they're
Speaker 8: quite rare, have become really important in terms of studying
Speaker 8: and understanding migraine because we can identify the specific changes
Speaker 8: that happened as a result of this one genetic mutation.
Speaker 8: One of those that I just want to shout out
Speaker 8: is called familial hemiplegic migraine, and this is characterized by migraines.
Speaker 8: They're hereditary and in addition to having all the features
Speaker 8: I just talked about of migraine and aura, they also
Speaker 8: cause a temporary hemiparesis, which means a one sided muscle
Speaker 8: weakness really like looks like a stroke.
Speaker 3: Yeah.
Speaker 8: And there are four different subtypes of this particular monogenic
Speaker 8: migraine syndrome, and they're caused by missense mutation in genes
Speaker 8: that are involved in neurotransmitter function, specifically in these vaulted
Speaker 8: gated ion channels. And I know that that's a lot
Speaker 8: of like BIOCHEMI words, but the point is that it's
Speaker 8: these specific like ion channels that are responsible for passing
Speaker 8: information in our brain that are involved at least at
Speaker 8: this level of migraine. So it gives us a lot
Speaker 8: of idea on potent targets for migraine treatment, both for
Speaker 8: people with these gene disorders as well as migraines. In general.
Speaker 3: That's that's really interesting.
Speaker 8: Yeah. So there's a lot of work on, like mice
Speaker 8: model studies and things like that with these type of
Speaker 8: migraine disorders. But I'm not done.
Speaker 3: Okay, Can I ask a question before we go off?
Speaker 8: Yeah?
Speaker 3: Okay, So it was when you mentioned abdominal migraines and
Speaker 3: I remembered I wanted to ask about, like why the
Speaker 3: nausea and vomiting and how, at least I read in
Speaker 3: some historical accounts people felt better after vomiting and then
Speaker 3: everything was fine, which, like I'm sure is not a
Speaker 3: universal truth. But is it just that, like there are
Speaker 3: pathways that are connected.
Speaker 8: So yes, In part, it's because these trigeminovascular complex afferent nerves,
Speaker 8: the ones that are going from parts of our brain
Speaker 8: to other parts of our brain and carrying signals with them,
Speaker 8: are going to parts of our brain that might be
Speaker 8: involved with causing nausea, like involved with maybe our vestibular
Speaker 8: system or something. But it's also because the spinal trigeminal
Speaker 8: nucleus in our brain stem, in addition to receiving information
Speaker 8: from our trigeminal nerve, it also gets information from a
Speaker 8: bunch of other nerves like our facial nerve, our glossophringal nerve,
Speaker 8: and our vagus nerve, which is our main parasympathetic nerve.
Speaker 8: And so whenever you have a mess up in our
Speaker 8: parasympathetic system, you can have a lot of very generalized symptoms.
Speaker 8: Right now, why would people feel better after they barf?
Speaker 8: I don't, I don't know, correct, But yeah, that's so,
Speaker 8: it's it's all complicated, it's all involved. But if all
Speaker 8: of that wasn't enough, as I kind of briefly mentioned
Speaker 8: when you brought up stroke, Aaron, there are also associations
Speaker 8: that are not well understood mechanistically but definitely seem to
Speaker 8: exist epidemiologically between migraine and a bunch of neurologic and
Speaker 8: psychiatric disorders. This includes epilepsy, it includes stroke, depression, anxiety,
Speaker 8: and probably more that I'm not mentioning. And one of
Speaker 8: the things that kept coming up in everything that I
Speaker 8: read that was so interesting about these relationships is that
Speaker 8: they're often described as bidirectional. For example, having an episode
Speaker 8: of major depressive disorder puts one at higher risk of
Speaker 8: having migraine, and having migraine puts one at higher risk
Speaker 8: of having major depressive disorder. At least based on some
Speaker 8: epidemiological studies, like in both directions.
Speaker 3: That sounds like a horribly vicious cycle. How do you
Speaker 3: do exactly break out of that? Can you? Right?
Speaker 8: And the same is true for epilepsy. Migraine and epilepsy
Speaker 8: are these comorbid conditions that seem to similarly have this
Speaker 8: bidirectional relationship, which maybe suggests some underlying similarity in the
Speaker 8: path of physiology, but we don't know. And it's also
Speaker 8: associated with an increased risk of stroke, especially in the
Speaker 8: case of migraine with aura, and specifically in the highest
Speaker 8: risk in people assigned female at birth under age fifty.
Speaker 8: And then there's triggers. Yeah, when it comes to migraine triggers,
Speaker 8: there's not really one thing that is true for all
Speaker 8: individuals with migraine, and we don't know because we know
Speaker 8: so little about the mechanisms of migraine initiation. We don't
Speaker 8: know how triggers that people may have identified in themselves
Speaker 8: trigger a migraine in them or in anyone else. But
Speaker 8: there are some things that seem to be relatively common
Speaker 8: triggers for most people that experience migraines, and these are
Speaker 8: things like stress, which could be emotional or physical stress,
Speaker 8: lack of sleep or poor sleep quality including jet lag,
Speaker 8: and hormonal fluctuations, in particular estrogen or a withdrawal of
Speaker 8: estrogen compared to where you were at previously. This is
Speaker 8: often a huge precipitate or trigger, especially for people who menstrate.
Speaker 8: We have very significant hormone fluctuations on a cyclic basis,
Speaker 8: So for some people that means increases in migraines with periods.
Speaker 8: For some people, pregnancy and breastfeeding causes a decrease in
Speaker 8: migraine symptoms, and then menopause causes an increase in migraines,
Speaker 8: whereas postmenopause might be a decrease or an elimination entirely
Speaker 8: of migraines.
Speaker 3: It's like, it's just not complicated at all, so straightforward. Yeah,
Speaker 3: and I'm sure consistent for every person I know.
Speaker 8: Yeah, totally.
Speaker 3: You can predict it, right, Yeah, totally. And how are
Speaker 3: hormones thought to be related? Don't now?
Speaker 8: Okay, oh, Aaron, not a clue. I mean we think
Speaker 8: that it's estrogen. What is estrogen doing or what is
Speaker 8: the withdrawal of estrogen doing, like the sudden decrease in estrogen.
Speaker 8: Don't know, don't know, no idea, and it's not like
Speaker 8: it's universal. Right, Not only that not everyone who mens
Speaker 8: streets has a migraine, but even people who do menstraight
Speaker 8: who get migraines may or may not have any association
Speaker 8: with their mensies. So it's it's not even close to universal.
Speaker 3: We have no idea what's happening?
Speaker 8: Yeah, and I mean and yet we know so much
Speaker 8: more Like it used to be thought that it was
Speaker 8: all about vasodilation and it was all vascular and it's not.
Speaker 8: So we know a lot more than we did, and
Speaker 8: you're right, we still know so little. The good news
Speaker 8: is that what we do know has led to the
Speaker 8: creation of a lot more effective medicines for treatment of migraines.
Speaker 8: So despite the fact that there's a lot that we
Speaker 8: don't know, there is good news to be had, and
Speaker 8: that is that migraines for many people are treatable. There's
Speaker 8: a number of different medicines. Some of them, like the
Speaker 8: trip dands work at the five HT or the serotonin
Speaker 8: receptors which cause vasoconstriction and inhibit the release of a
Speaker 8: whole bunch of neurotransmitters, including CGRP and others, and then
Speaker 8: there's newer medications that you've probably seen commercials for if
Speaker 8: you don't pay for premium Hulu like me, Like ubrel
Speaker 8: V and ner Tech. These medicines are specifically inhibitors of
Speaker 8: that CGRP peptide that we talked about. And then we'll
Speaker 8: talk in the current events section about other modalities that
Speaker 8: have come up and how much research is being done. Yeah,
Speaker 8: none of these treatments are perfect, but there are a
Speaker 8: lot of options. So, Aaron, tell me, how did we
Speaker 8: get here? How do I even ask that question?
Speaker 7: Yeah?
Speaker 3: How do I even answer it? I guess we'll find
Speaker 3: out after the break. Okay, migraines, What are they, what
Speaker 3: causes them, who gets them, how to retreat them? So
Speaker 3: Ori Aer, and I'm not going to ask you to
Speaker 3: redo the entire biology section. You're like, wait, I thought
Speaker 3: that always done?
Speaker 8: Like I answered some of those Yeah, yeah.
Speaker 3: So you already gave us the answers to what we
Speaker 3: know or what we think we know about migraines today.
Speaker 3: But the answers to all of those questions like whether
Speaker 3: or not aura has to be present for something to
Speaker 3: be considered a migraine, or whether migraines are caused by
Speaker 3: vascular or neurological changes, or if they have a physiological
Speaker 3: basis at all, those are not going to be the
Speaker 3: same throughout the history of migraine and how those answers
Speaker 3: evolve can tell us more about what was going on
Speaker 3: in the medical field or even society more broadly than
Speaker 3: it can tell us about the path of physiology of migraines.
Speaker 3: To be honest, it can tell us about what new
Speaker 3: ideas were popular at certain times or what new discoveries
Speaker 3: were made. Like for instance, when allergies or allergens were
Speaker 3: first identified as a concept, many physicians thought, hey, maybe
Speaker 3: migraines are caused by allergens, and they tried desensitization as
Speaker 3: a result, like allergy shots, or when hysteria was a
Speaker 3: popular diagnosis, it was you bring this on yourself, and
Speaker 3: you know, the advice was just don't be so stressed out,
Speaker 3: don't be so overworked if you want to prevent migraines,
Speaker 3: like just just don't work so hard, chill out, just
Speaker 3: just chill out. Yeah. Or when you're finding earthworms crop
Speaker 3: up as an ingredient for migraine treatment, that's a sign
Speaker 3: you're probably in the medieval period in Europe, we'll get there.
Speaker 3: Humans have always tried to explain diseases or other phenomena
Speaker 3: within the bounds of whatever knowledge we currently have, and
Speaker 3: the way we treat those diseases is heavily influenced by
Speaker 3: popular ideas about what their causes are. We still do that,
Speaker 3: and it's easy to lose sight of that that our
Speaker 3: current perception of migraine is only the latest in a
Speaker 3: long line and is subject to change and likely will change,
Speaker 3: hopefully for the better. But before you can tell us
Speaker 3: about what those positive changes might be, let's first go
Speaker 3: back to the early history of migraines so we can
Speaker 3: see just how far we've come, at least in some ways.
Speaker 3: And I want to give a huge shout out to
Speaker 3: the book that I used as my primary source for
Speaker 3: this history section, and that is Migraine, a History by
Speaker 3: Catherine Foxhall. It's a great read, and I'll definitely be
Speaker 3: quoting from it. It shouldn't surprise you even just how
Speaker 3: incredibly prevalent they are to learn that migraines have been
Speaker 3: known about, written about, experienced, treated for thousands of years.
Speaker 3: You can find mentions of migraines in basically any ancient
Speaker 3: medical text from any part of the world. The Ebers
Speaker 3: Papyrus from around fifteen fifty BCE describes extreme pain in
Speaker 3: one half of the skull that should be treated by
Speaker 3: anointing the head with the skull of catfish fried in
Speaker 3: oil or fat for four days. Of course, I don't
Speaker 3: know if that meant fried for four days or just
Speaker 3: like anointed. I'm guessing anointed for four days.
Speaker 8: I would have guessed fried for four days. So that's fascinating.
Speaker 3: Oh okay. In ancient China, migraines were treated with acupuncture.
Speaker 3: In ancient Greece bloodletting. And while it has been often
Speaker 3: suggested that tripanning was done throughout the ancient world to
Speaker 3: relieve the pain during a migraine, specifically so trepanning like
Speaker 3: drilling a hole, cutting a hole into your skull, there
Speaker 3: isn't really much in terms of evidence supporting that that
Speaker 3: it was specifically for migraines.
Speaker 8: It's for dust. Everything I know about trapani is from
Speaker 8: the Capital.
Speaker 3: Compass, and trepanning was definitely done, but whether or not
Speaker 3: it was for migraines probably will never know. If anything,
Speaker 3: tripanning was used specifically for migraine. More in the twentieth century,
Speaker 3: than in ancient times, at least as far as we know. Yeah, okay, okay,
Speaker 3: of course I can't leave the Hippocratic texts out of this.
Speaker 3: And it's in these texts from the fifth century BCE
Speaker 3: that we find our first clear description of migraine with
Speaker 3: aura a young man phoenix with quote flashes like lightning
Speaker 3: in his eye, usually the right And when he had
Speaker 3: suffered that a short time, a terrible pain developed towards
Speaker 3: his right temple, then in the whole head, and then
Speaker 3: into the part of the neck where the head is
Speaker 3: attached behind the vertebra, and there was stretching and hardness
Speaker 3: around the teeth. He kept trying to open them, straining
Speaker 3: vomits whenever they occurred, averted the pains I have described
Speaker 3: and made them more gentle. Phlebotomy helped, okay. About five
Speaker 3: hundred years after this description, Galen originated the term hemicrania
Speaker 3: to describe a condition a syndrome really wasn't like considered
Speaker 3: a disease. It was more of a syndrome, I guess,
Speaker 3: where half of your head was in pain and sometimes
Speaker 3: associated with stomach disturbance. Hemicrania turned into emigrania in Latin
Speaker 3: and Middle English, and then to migran in medieval Welsh,
Speaker 3: and then to magrime, and then we see all sorts
Speaker 3: of variations like migrim, migrime, migrime, like the spellings.
Speaker 8: Are all all over the place, slonky.
Speaker 3: Yeah, And the French word migraine began to be used
Speaker 3: more widely in medical literature starting around the eighteen seventies.
Speaker 3: So yeah, and the widespread use of these names for migraine,
Speaker 3: and all of the variations of these names, I think
Speaker 3: it clearly shows that migraine was not some obscure condition.
Speaker 3: It was highly recognizable and extremely common. But what was it?
Speaker 3: What did people think caused it? Aaron, I'm sure you
Speaker 3: can guess with the leading hypothesis for the cause of
Speaker 3: migraines from like ancient times until I don't know, seventeen
Speaker 3: hundreds or.
Speaker 8: So, something like humors being off.
Speaker 3: Yes, so I knew that all my talk of the
Speaker 3: humoral theory of disease has paid off so much. I
Speaker 3: feel like this season especially Yeah, basically an imbalance in humors.
Speaker 3: In the case of my it was attributed to an
Speaker 3: excess of bilious humors yellow bile and youth and black
Speaker 3: bile in adulthood, and so it follows then that treatment
Speaker 3: involved getting the humors back into balance. For example, consider
Speaker 3: this somewhat complicated treatment, aren't they always from an old
Speaker 3: English medical text called Bald's Leech Book from nine to
Speaker 3: fifty CE. I know, I want a copy of this
Speaker 3: me too. Quote for ache of half the head, take
Speaker 3: the red nettle of one stalk, bruise it, mingle with
Speaker 3: vinegar and the white of an egg. Put all together,
Speaker 3: anoint therewith. For a half head's ache, bruise and vinegar
Speaker 3: with oil the clusters of the loris. Smear the cheek
Speaker 3: with that. For the same take juice of rue ring
Speaker 3: on the nostril, which is on the sore side. For
Speaker 3: a half head's ache, take dust of the clusters of
Speaker 3: laurel and mustard, Mingle them together, Pour vinegar upon them,
Speaker 3: smear that with the sore side, or mix with wine
Speaker 3: the clusters of laurel, or rub fine in vinegar the
Speaker 3: seed of rue. Put equal quantities of both. Rub the
Speaker 3: back of the neck with that.
Speaker 8: Are those for like all just different options? Yeah you
Speaker 8: have available to you? Wow, okay, right, yeah.
Speaker 3: And okay, So first of all, there is actually a
Speaker 3: logic behind these ingredients because in general, with the humoral
Speaker 3: theory of disease, you were supposed to treat a condition
Speaker 3: with ingredients that had the opposite qualities of that disease.
Speaker 3: If migrain was thought to be a cold, moist condition,
Speaker 3: you would prescribe dry, hot ingredients like nettles and mustard seed. Okay,
Speaker 3: why so very many options. Again, there's a reason for it.
Speaker 3: Not all plant or animal ingredients would have been available
Speaker 3: year round. If a recipe calls for a fresh nettle
Speaker 3: and you're in the middle of winter, like, where are
Speaker 3: you going to get that? Or even if you just
Speaker 3: run out right. Yeah, And the availability of ingredients would
Speaker 3: have also changed as trade became more widespread and more
Speaker 3: herbs and spices were introduced, which I think is so
Speaker 3: interesting to think about, Like you can sort of track
Speaker 3: how trade influenced home remedies for certain conditions over time.
Speaker 8: Yeah, that's super interesting. Yeah, and the seasonality part too. Yeah.
Speaker 3: So let's see what kind of created solutions people came
Speaker 3: up with. So one from thirteenth century Whales is to quote,
Speaker 3: eat a baked or roasted hare's brain stuffed with rosemary flowers,
Speaker 3: followed by sleep end the quote.
Speaker 8: I uh uh, I mean don't do that. I still
Speaker 8: feel like from our preance episode, like just don't eat brains.
Speaker 3: Don't eat brains. That's a pretty good rule. Yeah. Yeah,
Speaker 3: yet another remedy. Not sure where it's from. Quote we
Speaker 3: anoint the temples, not nostrils, and pulsating veins with rose
Speaker 3: water together with the milk of a woman who is
Speaker 3: nursing a male child, and we induce sleep. End quote.
Speaker 8: Oh yi okay, uh huh.
Speaker 3: Uh huh yep, yep, how about that. Gargling with all
Speaker 3: sorts of mixtures of things and blood letting were also
Speaker 3: really common treatments. And which side of the body you
Speaker 3: bled from and how much, and what time of day,
Speaker 3: what time of year. All of these things could be
Speaker 3: adjusted to treat migraines specifically, which I think is interesting
Speaker 3: to think about.
Speaker 8: It's really interesting. I also kind of wonder with blood letting,
Speaker 8: like how much blood I've wondered this for a while,
Speaker 8: like how much blood would they let number one? And
Speaker 8: I actually wonder if there would be any benefit if
Speaker 8: you let out enough that then you had vasoconstriction. That
Speaker 8: seems like a bad I plan. Yeah, I just kind
Speaker 8: of wonder.
Speaker 3: So I can't remember. I have come across actual quantities,
Speaker 3: but I don't remember anything at this point in time,
Speaker 3: and I think it was pretty variable.
Speaker 2: Yeah.
Speaker 8: It just feels like you would have to do a
Speaker 8: lot for it to have any kind of effect.
Speaker 3: Yeah, and then you're just, you know, inviting a whole
Speaker 3: host of other problems.
Speaker 8: Yeah, into your life, et cetera.
Speaker 3: Yeah, yep, okay, Okay. But besides bloodletting, which was actually
Speaker 3: really common, another oddly common ingredient was what I mentioned earlier, earthworms.
Speaker 8: Yeah, what okay?
Speaker 3: Quote, take six spoonfuls of the gall of an ox
Speaker 3: or cow. Put there too, two spoonfuls of the powder
Speaker 3: of the long worms of the earth, and the powder
Speaker 3: of half a nutmeg grated. Boil all these together upon
Speaker 3: a chafing dish of coals until it be so thick
Speaker 3: as you may spread it upon a cloth. Then take
Speaker 3: a double linen cloth and cut it fit for your forehead,
Speaker 3: and as it may cover the temples, spread this upon
Speaker 3: it and lay it to your forehead, lukewarm, and let
Speaker 3: it lie until it do fall off itself. So in
Speaker 3: case you missed it, ground up earthworms, the long worms
Speaker 3: of the earth made into a paste that you put on.
Speaker 8: Your forehead with some like goat cow parts of cowcall stuff. Yeah.
Speaker 8: Why why?
Speaker 3: Why you can find earthworms in all kinds of remedies
Speaker 3: for things like constipation, jaundice, fevers, or other diseases of
Speaker 3: the head and brain, like throughout the medieval period again
Speaker 3: why Yeah? And I feel like we've come across so
Speaker 3: many of these, you know, a very strange to us
Speaker 3: combination of ingredients, and we're just like, haha, how weird.
Speaker 3: Moving on. But in this book was the first time
Speaker 3: that I've actually come across an explanation for why earthworms,
Speaker 3: for example, Okay, there is a reason, and honestly I
Speaker 3: kind of like it. I think it's very I think
Speaker 3: it's very interesting. Earthworms, because they lived in the dirt
Speaker 3: feeding on rotten matter, were believed to also eat or
Speaker 3: consume the rotting matter in your body that caused whatever
Speaker 3: disease you had.
Speaker 5: Huh.
Speaker 3: And so if migrains were caused by like rotting or
Speaker 3: toxic or putrefied stuff in your head, then that earthworm
Speaker 3: paste in theory would have eaten up the putrefying matter.
Speaker 6: Huh.
Speaker 3: Yeah. And earthworms weren't alone in this like other creatures
Speaker 3: that were quote unquote bread of putrefaction, like earwigs and snails,
Speaker 3: were also often used in remedies to like get the
Speaker 3: toxins out of you, how putrefaction? Yeah, okay. Up through
Speaker 3: the late seventeen hundreds or so, it seems like the
Speaker 3: vast majority of these migraine treatments, with the exception of bleeding,
Speaker 3: consisted of recipes that you could make at home with
Speaker 3: ingredients that you could find relatively easily. And that's evidenced
Speaker 3: by the fact that migraine treatments found their way into
Speaker 3: many home remedy books during the fifteen hundreds and sixteen hundreds,
Speaker 3: also showing once again how common migraines were. In one
Speaker 3: there was even a diagnostic tool where you were supposed
Speaker 3: to be able to like I didn't quite understand it,
Speaker 3: but it was like, how much I think of your
Speaker 3: hand or your thumb you can fit into your mouth?
Speaker 3: What during a migraine? Because if you can't fit however
Speaker 3: many knuckles in, then you had a migraine.
Speaker 8: Because you couldn't like open your mouth, could open your mouth?
Speaker 3: Yeah.
Speaker 8: Interesting.
Speaker 3: Yeah. The author of Migraine a History pointed out another
Speaker 3: interesting aspect of migraine treatments from the Mead, Evil and
Speaker 3: beyond times, which is that while the diversity of treatments,
Speaker 3: both in terms of methods and ingredients for migraines seems
Speaker 3: completely never ending, they all share one feature. There are
Speaker 3: no magical or religious elements in them. Migraines had a
Speaker 3: physical basis and were treated as such.
Speaker 8: That's fascinating.
Speaker 3: Yes, it is because it didn't stay that way.
Speaker 8: Yeah, I can imagine, because I feel like migrain has
Speaker 8: so much similarity to things that we've covered in the
Speaker 8: past that absolutely did not have the consideration of a
Speaker 8: real physical basis.
Speaker 3: Uh huh. It's so amazing to me given the stigma
Speaker 3: and the shame and the bias surrounding migraines today, even
Speaker 3: though we know that there is physical basis for them,
Speaker 3: how much disregard how much dismissal there is when for
Speaker 3: the the vast majority of its history from ancient times
Speaker 3: through the early to mid seventeen hundreds or so, the
Speaker 3: prevailing medical beliefs around migraines didn't change all that much.
Speaker 3: It had a physical basis. It came down to humors.
Speaker 8: Wow.
Speaker 3: Yeah, But like we've seen with many other diseases, especially
Speaker 3: chronic diseases that we've covered on the podcast like asthma
Speaker 3: and epilepsy, come to mind. Once medicine became more centralized
Speaker 3: and commercialized as people moved into cities in the late
Speaker 3: seventeen hundreds and into the eighteen hundreds, perceptions of migraine
Speaker 3: began to shift. It started with patent medicines taking the
Speaker 3: home out of home remedy and making concoctions available for
Speaker 3: people to purchase and doctors to patent and prescribe. Then,
Speaker 3: as hospitals were increasingly built and high population densities and
Speaker 3: cities meant that doctors could see really orders of magnitude
Speaker 3: more patients in a year than in past times, they
Speaker 3: started to observe more about migraines, how frequently they occur,
Speaker 3: how long they last, what age they usually first happen,
Speaker 3: the range of symptoms. And armed with these new observations,
Speaker 3: they began to draw conclusions about who was getting migraines
Speaker 3: and why. Were migraines just a cost of social progress
Speaker 3: in temperance, sedentary lifestyles, lack of restraint, urban living. All
Speaker 3: of these things the negative side of social progress, were
Speaker 3: thought to contribute to the rise of quote unquote nervous conditions,
Speaker 3: something that we've absolutely talked about on the podcast in
Speaker 3: terms of at least gout and asthma. Essentially, the view
Speaker 3: was that as society grew more corrupted, so did our bodies.
Speaker 3: Was it a wandering uterus?
Speaker 8: Perhaps?
Speaker 3: Probably? Was it being to creative? Could be what? Yeah,
Speaker 3: not getting a break from the kids, or being afraid
Speaker 3: to delegate household yours? Oh god, sure, I know right
Speaker 3: it is I I boil, I know yep. The perception
Speaker 3: of migraine, at least among the people writing about them
Speaker 3: male physicians, of course, shifted from a legitimate medical condition
Speaker 3: with a real physiological basis, even if it was thought
Speaker 3: to be humoral imbalance, to first a social and then
Speaker 3: later on a personal failing. And part of this was, ironically,
Speaker 3: because physicians were paying more attention to this condition and
Speaker 3: taking note of other symptoms like gipset or dizziness as
Speaker 3: pain as the primary feature took a back seat. The
Speaker 3: delegitimization of migraines in the late seventeen hundred and throughout
Speaker 3: much of the eighteen hundreds shifted who was responsible for
Speaker 3: managing this condition. It was no longer the doctor that
Speaker 3: had to figure out the correct course of treatment. It
Speaker 3: was now on the person themselves. If only they didn't overeat,
Speaker 3: if only they ate at more normal times, if only
Speaker 3: they didn't drink as much, didn't lays around as much,
Speaker 3: didn't work so hard, exercised more, exercise less, studied more studied, less,
Speaker 3: slept more. We're less ambitious, we're less sensitive, less feminine, stronger.
Speaker 3: Then maybe, just maybe they wouldn't bring this on themselves.
Speaker 3: Oh Okay, I.
Speaker 8: Know, I know, I'm not surprised by it, but it's
Speaker 8: still upsetting.
Speaker 3: Is a very upsetting. I know what had once been
Speaker 3: a humoral imbalance was now a nervous disease. And I'm
Speaker 3: not talking about like a neurologic disease that we think
Speaker 3: of today. I'm talking about the nineteenth century idea of
Speaker 3: a nervous disease, of which there were many different types,
Speaker 3: and nerves could be affected by any number of things,
Speaker 3: according to these physicians, and these things, and thus the
Speaker 3: nerves themselves were more under a person's control. But those things,
Speaker 3: what things affected nerves, of course, depended on the person.
Speaker 3: And with this increased attention on migraines, physicians began to
Speaker 3: split them up into different types, often gendered. For example,
Speaker 3: so called anemic migraines affected quote mothers in the lower
Speaker 3: classes of life end quote, whose bodies were quote hourly
Speaker 3: drained by lactation end quote. But don't worry. If you
Speaker 3: were a woman in a higher class, you could still
Speaker 3: get migraine just called neuralgic headache, which were quote undoubtedly
Speaker 3: hysterical end quote in origin.
Speaker 8: Ai yeay yay yi.
Speaker 3: But also it was just the domestic life in general
Speaker 3: that gave women so many migraines. Quote, the anxious forecasting
Speaker 3: and much serving, which slowly undermined the nervous energies of
Speaker 3: many wives and mothers end quote. Working class and mothers.
Speaker 3: Working class men got migraines after being exhausted from quote
Speaker 3: unquote excessive hours of labor or working in the quote
Speaker 3: unwholesome and ill ventilated workshops and dwellings of our crowded
Speaker 3: towns end quote. But for men of a somewhat higher
Speaker 3: social grade, it was generally using your brain too much,
Speaker 3: like reading too much, writing too much, working in legal
Speaker 3: chambers or the counting house, too much competition, the excitement
Speaker 3: of the university and professional life, the anxiety that came
Speaker 3: from too much ambition and so on. It could be
Speaker 3: literally anything, but it's always the person's fault, and the
Speaker 3: remedies for all these different types of migrain were fairly straightforward.
Speaker 3: A break from the stressors, which could include maybe a
Speaker 3: more nutritious diet, not working or studying as much, or
Speaker 3: for an overworked mother, a forced absence from the home. Yeah,
Speaker 3: that happened, okay, And they're just like, you're afraid to delegate.
Speaker 3: There's tons of people that can help out with your kids,
Speaker 3: like just leave them. And whether or not any of
Speaker 3: these things were practical, Like let's say that you are
Speaker 3: working in one of these factories. It's not like you
Speaker 3: could just be like, oh yeah, let me just take
Speaker 3: some days off work, No problem, I'll take a vacation
Speaker 3: to the countryside where the fresh air, the fresh sea
Speaker 3: air will do me good.
Speaker 8: It's not like they were able to use this for
Speaker 8: like unionizing efforts and actually getting better working conditions.
Speaker 3: I absolutely not. Yeah, yeah, but that didn't These like
Speaker 3: practical things didn't matter to the physician prescribing them, right,
Speaker 3: And the physicians prescriptions, by the way, were not limited
Speaker 3: to changes in lifestyle. The rise of hospitals and other
Speaker 3: medical institutions like asylums provided ample opportunities for physicians to
Speaker 3: test out experimental treatments just the latest and greatest, including opium,
Speaker 3: potassium bromide, arsenic quinine, and cannabis, which was actually a
Speaker 3: favorite among many doctors and patients, but nothing reliably worked,
Speaker 3: as I'm sure you could guess. And contributing to this
Speaker 3: lack of meaningful progress in migraine research, at least in
Speaker 3: terms of treatment through the late nineteen and into the
Speaker 3: twentieth century was the lack of certainty in diagnosis. As
Speaker 3: a quote unquote invisible illness, people with migraine could appear
Speaker 3: healthy even in the midst of a horrific attack, which
Speaker 3: made it easier for physicians to dismiss their pain or
Speaker 3: not take it seriously, with some physicians saying that, oh,
Speaker 3: someone who is in that much pain can't be relied
Speaker 3: upon to recount their experiences accurately. Okay, not sick enough
Speaker 3: to be considered chronically ill, but not well often enough
Speaker 3: to be healthy. Something like that. It was just like
Speaker 3: middle ground pain as a subjective experience couldn't be trusted
Speaker 3: by these physicians as the sole diagnostic criterion for migraine,
Speaker 3: and so they turned to aura. Visual disturbances had long
Speaker 3: been associated with migraine, but hadn't really been studied in
Speaker 3: a systematic way until the mid to late eighteen hundreds,
Speaker 3: when two scholarly men, British mathematician, astronomer and chemist Sir
Speaker 3: John Herschel and physician Hubert Airy, presented their experiences of
Speaker 3: quote unquote ocular spectra at a couple of scientific meetings.
Speaker 3: They described disruptions in visions that could be induced by
Speaker 3: the shining of a strong light and a quote singular
Speaker 3: shadowy appearance end quote that sat at the corner of
Speaker 3: vision and then came into full view with kaleidoscopic, colorful
Speaker 3: geometric patterns. Airy also shared a drawing of his visual disturbance,
Speaker 3: which he called hemiopsy, and his drawing, which was jagged
Speaker 3: swirling lines on a black background, became one of the
Speaker 3: most famous and recognizable illustrations of migraine aura, which had
Speaker 3: become front and center in migraine diagnosis and research as
Speaker 3: debates continued about whether the condition had a vascular or
Speaker 3: neurological basis, and effective treatments were of course still nowhere
Speaker 3: to be found, and that's how things remained for the
Speaker 3: first decades of the twentieth century. The pain from migraines
Speaker 3: took a backseat to aura, which had become romanticized, especially
Speaker 3: with people claiming all sorts of historical and religious figures
Speaker 3: must have had aura and migraine because their religious visions
Speaker 3: or drawings resembled aura. Hildegarde of Bingen, if that's how
Speaker 3: you say it, hopefully, a saint who lived in Germany
Speaker 3: in the twelfth century, was foremost among these and has
Speaker 3: been called the patron saint of migraines. And really her
Speaker 3: retrospective diagnosis kicked off a whole bunch more, including Moses Ezekiel, Daniel,
Speaker 3: Saint John, the Divine, Charles Darwin, Pablo Picasso, Rudyard Kipling,
Speaker 3: Virginia Wolf, etc. And I don't know the details of
Speaker 3: what went into each of these retrospective diagnoses, like what
Speaker 3: symptoms did they use. I think for Picasso they just
Speaker 3: looked at his drawings and they were like, yeah, sure,
Speaker 3: Like did he ever write about pain anyway? And of
Speaker 3: course it is possible that several or even all of
Speaker 3: these people had migraines. Migraines are incredibly prevalent after all.
Speaker 3: But the problem with these retrospective diagnoses was how they
Speaker 3: were used by some people to push this message, which
Speaker 3: was that a visual aura was the defining feature of
Speaker 3: migraines and that b people who had the most extreme
Speaker 3: visual disturbances with migraine were the quote clever, intellectual people
Speaker 3: endowed with the creative type of mind and quote yeah,
Speaker 3: and it furthered this idea of there being a quote
Speaker 3: unquote migraine personality, which had evolved from the gender and
Speaker 3: class stereotypes of the late nineteenth century Prepare yourself, my dear.
Speaker 3: According to the American physician Walter Alvarez from the mid
Speaker 3: twentieth century or so, the typical migraine patient was female,
Speaker 3: quote tense, perfectionist, hypersensitive, easily fatigued, and often depressed or
Speaker 3: disconnected end quote. They also had bad periods and quote
Speaker 3: unquote defective and poorly functioning pelvic organs. What but don't worry.
Speaker 3: She was also quote decidedly feminine and sexually attractive quote
Speaker 3: but with a masculine vibe. That quote causes her to
Speaker 3: act independently and to think dispassionately, much as does an
Speaker 3: able businessman.
Speaker 8: I can not.
Speaker 3: I know, I know, I hate it so much.
Speaker 8: Oh my god.
Speaker 3: Alvarez went so far as to claim that he could
Speaker 3: spot a migraine patient without even talking to them.
Speaker 8: I don't like this guy, and he was known in
Speaker 8: his ideas.
Speaker 3: There's many people as you can dislike. In the nineteen
Speaker 3: forty eight book Headache and Other head Pain, author neurologist
Speaker 3: Harold Wolfe wrote that his migraine patients had as children
Speaker 3: been quote delicate, shy, withdrawn, and obedient to their parents
Speaker 3: end quote, but also stubborn, and as adults they were
Speaker 3: quote unusually ambitious and preoccupied with achievement and success end quote.
Speaker 3: Unusually ambitious, unusually ambitious, They had a hard time delegating.
Speaker 3: They were impatient and resentful, cold, and aloof been brought
Speaker 3: on migraines by not adapting well to situations like going
Speaker 3: on vacation. Just like relax. You can't relax on vacation.
Speaker 3: You're going to get a migraine. You're going to give
Speaker 3: yourself a migraine.
Speaker 8: I want to highlight that, you said a book from
Speaker 8: nineteen forty eight. Uh huh, that was not long ago? No, yeah, okay.
Speaker 3: Another physician from around this time wrote that people with
Speaker 3: migraines had quote a personality that seeks and creates stress
Speaker 3: and a physiology that handles it poorly end quote.
Speaker 8: So yeah, it's really interesting because there's evidence now that
Speaker 8: some of the things that people have historically or even
Speaker 8: maybe personally identified as like potential triggers or things like
Speaker 8: quote unquote stress, et cetera, may actually be part of
Speaker 8: the prodromal phase of a migraine itself. So like, so
Speaker 8: it's really even more frustrating to hear like these, oh,
Speaker 8: you're you're causing yourself stress, Like it could genuinely be
Speaker 8: that people's brains are increasing certain stress responses or something
Speaker 8: in a way that's entirely outside of your control, and
Speaker 8: then a migraine follows.
Speaker 3: Like it's just yeah, as though, like all of these
Speaker 3: things are under someone's control anyway, right, Like be less stressed,
Speaker 3: try not to worry so much, just like, don't worry.
Speaker 8: That advice has helped no one ever.
Speaker 3: No, And so when you're met with this kind of
Speaker 3: dismissal and blame from someone who is supposed to be
Speaker 3: giving you health care, whom you are paying for health care,
Speaker 3: whom you look to as an expert how are you
Speaker 3: going to feel comfortable asking for help? It's so frustrating because,
Speaker 3: like I said, for the vast majority of human written history,
Speaker 3: migraines were handled as real medical problems with a physical basis,
Speaker 3: only to have that undermined by physicians who were probably
Speaker 3: projecting their own insecurities over not being able to effectively
Speaker 3: treat migraines or define them. And I have no doubt
Speaker 3: that contributing to this was the gender distribution in migraines,
Speaker 3: with women much more likely to experience them. This dismissive
Speaker 3: attitude towards migraines, the idea of a migraine personality or
Speaker 3: a taking center stage as a symptom. We're still feeling
Speaker 3: all of the effects from this today. And there's a
Speaker 3: book that I didn't get a chance to read for
Speaker 3: this episode, but I really want to read, called Not Tonight,
Speaker 3: Migraine and the Politics of Gender and Health by Joanna
Speaker 3: Kempner that goes into this in much more depth, and
Speaker 3: I'll link to it on our website. But this downplaying
Speaker 3: of migraines as just really bad headaches and sort of
Speaker 3: the casting off of pain, like dismissing pain as the
Speaker 3: feature for most migraines has contributed to the gap in
Speaker 3: research funds for migraine treatments and the lack of general
Speaker 3: awareness around the cause and especially the impact of migraines.
Speaker 3: They can be debilitating, incapacitating, excruciating, even with stress control,
Speaker 3: whatever that means, even with sufficient sleep, even with taking
Speaker 3: a break from the kids, even with medication, even with
Speaker 3: doing whatever else a doctor tells you not to do,
Speaker 3: so that you don't bring this on yourself. You can't.
Speaker 3: I'm just so frustrated, and I can't help but feel
Speaker 3: that doctors in the late nineteenth century in early twentieth
Speaker 3: century they took one look at migraine and thought, I
Speaker 3: don't know what this is. I can't treat this. Therefore
Speaker 3: it must not be real, or at the very least,
Speaker 3: it must not be as bad as they say, or
Speaker 3: it's probably a personal failing on their part, because I'm
Speaker 3: a trained medical professional and I can't admit that I
Speaker 3: don't know something or can't treat something. Let me read
Speaker 3: you one final quote from a physician, and then I'll
Speaker 3: get us off this rage train. Maybe. In nineteen o two, J. M.
Speaker 3: Aiken wrote in jama that quote, of all the common
Speaker 3: and much dreaded nervous diseases we recognize. None are less
Speaker 3: perfectly understood than migraine. Nor is there any other nervous
Speaker 3: disorder which is so disastrous to the physician's ability for treatment.
Speaker 3: It is easy to say what migraine is not, but
Speaker 3: difficult to define what it is end quote.
Speaker 8: I mean even just the framing of that as like
Speaker 8: this is hard for doctors.
Speaker 3: Oh yeah, And I didn't even get into like some
Speaker 3: of the gendered advertisements from the mid twentieth century for
Speaker 3: migraine treatment, where it's like geared towards doctors that are like,
Speaker 3: it's not just a problem for your female migraine patient,
Speaker 3: it's also a problem for you, kind of implying like
Speaker 3: she's complaining to you and she keeps seeking help, so
Speaker 3: prescribe her this.
Speaker 6: Wow.
Speaker 3: Oh wow, it's good stuff. Yeah. In the second half
Speaker 3: of the twentieth century, we did make substantial progress in
Speaker 3: understanding what migraine was, especially with the introduction of the
Speaker 3: International Classification of headache disorders in nineteen eighty eight, progress
Speaker 3: in what caused it, with the neurological framework sort of
Speaker 3: overtaking the vascular one and then kind of being integrated
Speaker 3: with this new neuro vascular framework, and we also made progress,
Speaker 3: a lot of progress in how to treat it, first
Speaker 3: with the introduction of ergotamine and then like migral tablets,
Speaker 3: which was a combination of ergotamine, caffeine, and cyclazine introduced
Speaker 3: in the nineteen fifties. And then also another treatment that
Speaker 3: you mentioned, which was introduced in the nineteen eighties was
Speaker 3: the trip dans, with the first one being sumatriptan. And
Speaker 3: so we've come a long way in our understanding and
Speaker 3: prevention slash management of migraine, but we clearly have so
Speaker 3: far to go still, not just in treatments and making
Speaker 3: those treatments accessible for everyone who needs them, but also
Speaker 3: in reducing stigma, shame, and blame surrounding migraines, like believing
Speaker 3: people what a concept? Why is it so hard? Why
Speaker 3: is pain the most dismissed thing?
Speaker 8: I feel like we talked about this in our Endometrios
Speaker 8: this episode a lot as well.
Speaker 3: Yeah, Yeah, also hugely gendered aspect there, likely.
Speaker 8: Because you can't see pain, like when we talk about
Speaker 8: being able to measure something right, right, but.
Speaker 3: We also can't see aura. Yeah that's true, Or like nausea.
Speaker 8: But but you can see vomiting.
Speaker 3: You can see vomiting. Yeah.
Speaker 8: Yeah.
Speaker 3: I think that I spent so much time sort of
Speaker 3: in the earlier history of migraines because I really did
Speaker 3: want to get across the point that we used to
Speaker 3: be better are at this. I mean, yes, it was
Speaker 3: the humoral theory of disease, but it was like, oh,
Speaker 3: here's this real thing. Here are some real treatments for it.
Speaker 8: Yeah.
Speaker 3: Oh, but maybe it's not real. Maybe it's all in
Speaker 3: your head, and it's just it's so many diseases are
Speaker 3: like this that we've covered on the podcast.
Speaker 7: You know.
Speaker 3: We've talked about asthma, We've talked about lupus, we've talked
Speaker 3: about epilepsy, we've talked about, of course, endometriosis. That have
Speaker 3: undergone this shift that I think coincides with when medical
Speaker 3: knowledge was increasing overall but not necessarily shedding any light
Speaker 3: on those conditions, and so rather than saying maybe it's
Speaker 3: something that we don't know about yet, it had to
Speaker 3: be put in this box of maybe it's in your head.
Speaker 3: I'm sure that we'll look back on this period of
Speaker 3: time with similar diseases that right now are classified as
Speaker 3: psychosomatic or whatever it is, you know, Like anyway, I'm
Speaker 3: at the very end of this gone on this rant,
Speaker 3: and now I should just stop myself and turn it
Speaker 3: over to you, Aaron.
Speaker 8: So but I love it, Aaron, I mean I hate it? Yeah?
Speaker 3: Oh yes, So where do we go from here? Oh?
Speaker 8: Okay, okay, let's take a break, take a breath, and
Speaker 8: we'll find out. Migrain is estimated to affect one billion
Speaker 8: people worldwide, depending on the paper that you read and
Speaker 8: what data you use, meaning if you consider definite and
Speaker 8: probable migraines based on those ICHD criteria, that's between fifteen
Speaker 8: percent of the global population or as high as thirty
Speaker 8: five percent of the general population having migraines each year.
Speaker 8: Thirty five percent arin if you include probable migraine.
Speaker 3: And that's every year. That's not lifetime.
Speaker 8: So this is yeah, annual prevalence. It's not incidents. We
Speaker 8: don't have great data on incidents, but that's annual prevalence. Now,
Speaker 8: across all age groups, prevalence of migraine is significantly higher,
Speaker 8: usually two to three times higher depending on age, in
Speaker 8: people who are assigned female at birth compared to peer
Speaker 8: people assigned mail and prevalence tends to peak usually in
Speaker 8: the thirties, but really age twenty five to forty, so
Speaker 8: this is young people being very significantly affected. Among people
Speaker 8: with active migraine, the median monthly attack frequency, so how
Speaker 8: many episodes of migraine per month is one point five
Speaker 8: but a quarter of people have weekly attacks. And remember
Speaker 8: that the total duration of a migraine attack can last
Speaker 8: up to a week. Oh my gosh, right, And up
Speaker 8: to five percent have chronic migraine, which again means fifteen
Speaker 8: headache days a month, eight of which meet criteria for migraine.
Speaker 8: So with all of that being said, it should come
Speaker 8: as no surprise, though this was shocking to me. The
Speaker 8: World Health Organization ranks migraine as the most prevalent disabling
Speaker 8: long term neurologic condition period and it's not necessarily because
Speaker 8: it's the most common. Even in terms of headaches, tension
Speaker 8: type headaches are far more common than migraine, but migraine
Speaker 8: is so disabling that, as an example, while tension type
Speaker 8: headache affects almost a billion more people worldwide, like eight
Speaker 8: hundred million more people than migraine, migraine causes six times
Speaker 8: as many estimated disability adjusted life years or years lived
Speaker 8: with disability.
Speaker 1: Whow.
Speaker 8: Migraine in twenty eighteen caused an estimated forty five million
Speaker 8: years lost to disability, compared to seven point two million
Speaker 8: for tension type headache. Oh my gosh, and the data
Speaker 8: hasn't changed changed much over the years. That estimate was
Speaker 8: from a twenty eighteen paper based on twenty sixteen data.
Speaker 8: Based on twenty nineteen data, it's an estimated forty two
Speaker 8: point one million years lost to disability. That's it's obscene, Yeah,
Speaker 8: especially because we have treatments. Migraine is the leading cause
Speaker 8: of disability worldwide for people younger than fifty years, especially
Speaker 8: for women. And I don't want to just go based
Speaker 8: on disability adjusted life years or years lost to disability,
Speaker 8: because we know that that's an imperfect metric. But I
Speaker 8: also have read that in studies that have looked based
Speaker 8: on survey data from the US at least on people's
Speaker 8: reported effect on their lives, that up to thirty percent
Speaker 8: of people who live with migraines say that it affects
Speaker 8: their careers in some way, thirty percent say that it
Speaker 8: affects their parenting in some way, and nearly fifty percent
Speaker 8: feel that it affects their relationships. Yeah, that's huge, and
Speaker 8: caveat that those numbers are based on US data, so
Speaker 8: we don't know the universality of that. But it's I mean,
Speaker 8: this is not a minor disorder.
Speaker 3: To live with, right, and like just living with that
Speaker 3: uncertainty and that unpredictability. Yeah, and planning. How can you
Speaker 3: plan around a migraine when you don't know if you're
Speaker 3: going to have one?
Speaker 8: Yep, exactly, Oh my gosh. If you're more interested in
Speaker 8: money and cost, In Europe, financial costs that are attributed
Speaker 8: to migraine are estimated at between fifty and one hundred
Speaker 8: and eleven billion dollars, and that was like fifteen years ago.
Speaker 8: And what's interesting is that in Europe the vast majority
Speaker 8: of that cost is estimated to be indirect cost, meaning
Speaker 8: not healthcare dollars, but dollars lost in other ways because
Speaker 8: of lost productivity at work, et cetera. Whereas in the US,
Speaker 8: direct costs are estimated at eleven billion dollars annually and
Speaker 8: indirect cost twelve billion dollars annually. Wow, So there's a
Speaker 8: lot of discrepancy there. I'm sure there's a whole podcast
Speaker 8: about that. So migraine is a massive issue, and most
Speaker 8: of the data that we have on migraine come from
Speaker 8: Europe and the US and high income countries, but migraine
Speaker 8: is a global phenomenon that affects people across the entire world,
Speaker 8: and in low and middle income countries. Not only do
Speaker 8: people tend to lack access to a lot of treatment
Speaker 8: or even diagnosis options, people are far less likely to
Speaker 8: be diagnosed accurately with migraine in low and middle income countries.
Speaker 8: We also have much less data to guide policy and
Speaker 8: to guide programs, and part of this is because the
Speaker 8: focus tends to be in low and middle income countries
Speaker 8: on other additionally pressing health issues, things things like TB
Speaker 8: and HIV, which are more common in low and middle
Speaker 8: income countries. But that's despite the fact that migraine is
Speaker 8: also causing massive amounts of disability in these countries as well.
Speaker 3: Right, And there's.
Speaker 8: Estimates from a whole bunch of different countries that indirect
Speaker 8: costs alone can be as much as two percent of
Speaker 8: gross domestic product annually WHOA because of migrain. Yeah, So
Speaker 8: when it comes to current research, it's a little hard for
Speaker 8: me to even know where to begin.
Speaker 3: Is that a good thing?
Speaker 8: I don't.
Speaker 3: I don't know, Okay.
Speaker 8: Sometimes in this section I'm able to say, like, here's
Speaker 8: this one new great thing that just happened or is
Speaker 8: on the horizon it's about to happen. I don't have
Speaker 8: that one great thing for migraine, Okay. But that's not
Speaker 8: because there haven't been great strides made in migraine research.
Speaker 8: There have been a number of really new drugs in
Speaker 8: the last year, really this year, in twenty twenty three,
Speaker 8: and in the last couple of years that have come
Speaker 8: down the pipeline. There have been new monoclonal antibodies that
Speaker 8: specifically target this CGRP pathway, and many of which are
Speaker 8: intended to be used as preventative treatment, so especially for
Speaker 8: people who have chronic migraine or just a high burden
Speaker 8: of migraine, you know, each week or each month, even
Speaker 8: if they don't meet criteria for chronic migraine preventative rather
Speaker 8: than just what are called abortive treatments or treatments made
Speaker 8: to be used when a migraine happens. Right, And there
Speaker 8: have also been other oral medications that includes that whole
Speaker 8: class called the jeptins, which are the ones that have
Speaker 8: commercials right now, like Ubrelv and Nurtec. I probably shouldn't
Speaker 8: use brand names, but whatever. These are things that also
Speaker 8: target that CGRP peptide. There's also a brand new nasal
Speaker 8: spray that targets the same peptide.
Speaker 3: Oh fascinating, I know.
Speaker 8: And there's a relatively new I think in twenty nineteen
Speaker 8: was when it was approved by the FDA, was a
Speaker 8: medicine in a class called ade tan, which are very
Speaker 8: similar to triptans, but they have less vasoconstrictive effects, which
Speaker 8: means less cardiac risk and therefore more people can probably
Speaker 8: use it. Cool, and then there are really creative things
Speaker 8: like botox injections, trigger point injections, neuromodulatory mechanisms, and probably
Speaker 8: a bunch more drugs coming down the pipeline as well.
Speaker 8: But there isn't like a silver bullet, and a lot
Speaker 8: of that is because there's still just so much that
Speaker 8: we don't know when it comes to migraine.
Speaker 3: Yeah.
Speaker 8: So some of the other big areas of research besides
Speaker 8: just therapeutics are things like identifying biomarkers, either blood biomarkers
Speaker 8: or imaging biomarkers. Things that we can identify on an
Speaker 8: MRI that can either predict the risk of migraine or
Speaker 8: predict treatment targets so that we can develop even other
Speaker 8: types of therapeutics.
Speaker 3: But in general, there's.
Speaker 8: A lot of mixed results when it comes to a
Speaker 8: lot of things with migraine research, but especially with this
Speaker 8: attempt at identifying various biomarkers. I think the thing that
Speaker 8: gives me hope is I will say that when I
Speaker 8: was researching for this episode, I found more very recent
Speaker 8: papers in like well regarded journals about migraine research than
Speaker 8: I have found for any of our recent episodes. Oh wow, Okay,
Speaker 8: like a lot. There's a whole series that came out
Speaker 8: in the Lancet three paper series that came out in
Speaker 8: twenty twenty one. There's Nature papers and New England Journal papers,
Speaker 8: like a lot of kind of high profile research that's
Speaker 8: really really recent when it comes to migraine. So that
Speaker 8: gives me hope that it's getting a lot more attention
Speaker 8: because we're recognizing what a massive issue it really is,
Speaker 8: that's migrain.
Speaker 3: Gosh, I hope we did it justice.
Speaker 1: Yeah?
Speaker 3: Is that enough?
Speaker 7: I don't know.
Speaker 3: I don't think so, tell Us, could it ever be enough?
Speaker 8: No?
Speaker 3: Luckily there's more reading.
Speaker 8: There's so much more. Let us tell you about it.
Speaker 3: I'm going to shout out again Migrain a History by
Speaker 3: Catherine Foxhall, and a'll link to it on the website.
Speaker 8: I have a lot of sources for this episode. A
Speaker 8: few that I loved were Migrain a Primer from Nature
Speaker 8: Reviews Disease Primers in twenty twenty two. There was also
Speaker 8: a paper titled Migraine and the Trigeminovascular System forty years
Speaker 8: in counting from the Lancet Neurology in twenty nineteen. Also
Speaker 8: I mentioned already, but there's a great series. It's three
Speaker 8: different papers about different aspects of migrain, from the epidemiology
Speaker 8: to disease characterization like biomarker research and approaches to management
Speaker 8: and emerging treatments that all came out in the Lancet
Speaker 8: twenty twenty one. We'll have a list of this and
Speaker 8: all of our sources from this episode and all of
Speaker 8: our episodes on our website This podcast will kill You
Speaker 8: dot Com under the episodes tab.
Speaker 3: We certainly will a big, huge, tremendous, incredible thank you
Speaker 3: to everyone who shared their experience, their story with migrain.
Speaker 3: We really can't thank you enough.
Speaker 8: Yeah, thank you. Thank you also to Bloodmobile for providing
Speaker 8: the music for this episode and every one of our episodes.
Speaker 3: And thank you to Leana Squalacci for the amazing audio mixing.
Speaker 3: Thank you to the Exactly Right Network, and thank you
Speaker 3: to you listeners. We hope that you, I don't know
Speaker 3: got something out of this episode learned something.
Speaker 8: I hope so know, let us know.
Speaker 3: We appreciate you.
Speaker 8: And a special shout out as always to our patrons.
Speaker 8: Thank you so much for your continued support. We really
Speaker 8: appreciate it.
Speaker 3: Yeah, thank you. Well. Until next time, wash your hands.
Speaker 8: You filthy animal elf.
Speaker 1: M um um.
Speaker 4: Um um
Speaker 8: U