Ouch! If you’ve ever stubbed your toe, gotten a paper cut or fallen off your bike, you know that getting hurt is no fun. Sometimes we can take medicine to help feel better, like ibuprofen. But how does that medicine know where to go in our bodies to stop the pain?

In this episode, Molly and kid co-host Skylar explore where pain comes from and chat with expert Dr. Amanda C de C Williams about why it’s useful. Then they’ll eavesdrop on an ibuprofen pill on its first day of work to find out how it does its job. And of course, an all new mystery sound!

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CHILD 1: You are listening to Brains On, where we're serious about being curious.

CHILD 2: Brains On is supported, in part, by a grant from the National Science Foundation.

MARC SANCHEZ: Ow.

SANDEN TOTEN: Ow.

MARC SANCHEZ: Ouchie. Ouchie. How did he do? Ow. Ow.

MOLLY BLOOM: Marc, Sanden, what are you doing?

MARC SANCHEZ: Oh, hey, Molly. We're just practicing what sounds we'd make when we get hurt.

SANDEN TOTEN: We know you're taping an episode about pain, so we figured, you might need some cool sound effects to make the show really pop, like this one, ooh, ouchy mama.

MOLLY BLOOM: I don't think we'll need more sound effects.

SANDEN TOTEN: Oh, you need more sound effects? Hey, Marc, what sound does a cat make if it accidentally bonks its furry little head on the leg of a chair?

MARC SANCHEZ: Meouch.

MOLLY BLOOM: Guys, I appreciate your enthusiasm, but I'm trying to tell you that--

MARC SANCHEZ: Oops, Sanden, I've got one. What does a coyote sound like if it accidentally gets a thorn in its paw, walking at night under the full moon?

SANDEN TOTEN: [HOWLING]

MARC SANCHEZ: [HOWLING]

Molly, do you have one for us?

SANDEN TOTEN: Come on, Molly.

MOLLY BLOOM: OK. What sound does a dog make when it accidentally slips on the just mopped kitchen floor?

MARC SANCHEZ: Bowowowowowow.

SANDEN TOTEN: Bowowowowowow.

[MUSIC PLAYING]

MOLLY BLOOM: You're listening to Brains On from APM Studios. I'm Molly Bloom. And my co-host today is Skyler from Windsor Mill, Maryland. Hi, Skyler.

SKYLER: Hi, Molly.

MOLLY BLOOM: Today's episode was inspired by a question that you sent to us.

SKYLER: Yeah. I was wondering how ibuprofen knows where to go in our bodies to stop pain.

MOLLY BLOOM: This is an excellent question. Ibuprofen is a medicine that also goes by other names like Motrin and Advil. It's also very similar to medicines like aspirin. Tylenol is another medicine that helps with pain, but that one works differently.

So Skyler, since you asked about ibuprofen, that's the one we're focusing on today. So Skyler, how did you think of this question?

SKYLER: Well, I have EOE, and I get really bad headaches as a side effect for it. So my dad got me an ibuprofen. And I was just wondering, how does this thing to go to my head and not to my foot?

MOLLY BLOOM: It's a great question. And can you tell us what is EOE?

SKYLER: It's eosinophilic esophagitis.

MOLLY BLOOM: And so what does that mean exactly?

SKYLER: Well, I've got little eosinophils in my esophagus, that make it hurt when I eat food, swallow. And there's lots of side effects, like headaches.

MOLLY BLOOM: So your esophagus, that's the long tube that moves food from your mouth to your stomach. And that's the part that hurts, sometimes. And you have some side effects but you take ibuprofen to help with the pain. And you were wondering, how does ibuprofen help me?

SKYLER: Yeah.

MOLLY BLOOM: Got you. So before we get into how ibuprofen works to stop pain, first, we need to understand how our bodies feel pain in the first place.

SKYLER: It's all about nerves.

MOLLY BLOOM: Exactly. Nerves are special cells in your body that send messages to your brain.

SKYLER: Cells are the building blocks of your body. Everything in your body is made up of different kinds of cells.

MOLLY BLOOM: There are nerve cells that tell your brain what you're seeing, hearing, and feeling. And there are special nerve cells whose entire job is to tell you when something hurts.

SKYLER: So the nerves that tell you that someone is holding your hand are different from the ones that tell you you just got a paper cut.

MOLLY BLOOM: To show how this works, let's use the most painful thing I can possibly imagine, stubbing your toe.

SKYLER: Oh, my gosh, yes. Why does it hurt so much?

MOLLY BLOOM: Skyler, let's pretend you're walking along. Can you hum for me?

SKYLER: Sure. [HUMMING]

MOLLY BLOOM: So Skyler is walking along, humming to herself, wondering what she'll have for breakfast tomorrow and which of a horse's legs would wear pants if horses wore clothes.

SKYLER: I have wondered that. Would a horse wear pants on all four legs or just the back ones? It's a mystery.

MOLLY BLOOM: So there she is, walking around her house in her nice warm wool socks when, [CLANG], bam, she stubs her big toe on the edge of the couch.

SKYLER: Ouch. Who put that couch there? I swear it used to be two inches to the left.

MOLLY BLOOM: Oof, sorry, Skyler. That big toe of yours is full of special nerve cells whose job it is to feel pain. So when you stub your big toe, [CLANG] the nerves send a message to your brain.

SKYLER: When it gets there, my brain is like, out, something smashed my toe.

MOLLY BLOOM: And it all happens very, very fast in a fraction of a second. It's the nerve's job to send a message to your brain when something happens that hurts your body.

SKYLER: This can happen when you get a splinter, eat a really spicy pepper.

MOLLY BLOOM: Or even get a sunburn. The pain nerves are telling your brain that some damage has happened in your body.

SKYLER: But why? Why does it need to hurt so much? Why couldn't it just be a little flutter, a little gentle, yoo-hoo, over here, a light spot of damage.

MOLLY BLOOM: To help us answer that question, we have a special guest, Dr. Amanda CDC Williams is an expert on pain from University College of London.

SKYLER: And she's here with us to answer some of our big questions about it. Hi, Dr. Amanda.

DR. AMANDA WILLIAMS: Hi, Skyler.

SKYLER: How does feeling pain help us?

DR. AMANDA WILLIAMS: Well, it helps us to-- firstly, to get away from whatever is hurting us, like a hot kettle or a sharp thorn or whatever it is quickly before we do more damage. And then it goes on hurting so we're careful for the next few days or few weeks, however it long-- long it takes to heal so we don't do any more damage, and we make sure it heals well and doesn't get infected and then create a bigger problem. So in that way, it's really, really helpful to feel pain, however unpleasant it is.

SKYLER: Wow, that's very interesting. What areas of our bodies can feel pain and which areas can't?

DR. AMANDA WILLIAMS: Well, almost all parts of your body can feel pain of some sort, but it's often different. So on your skin, you can feel sharp pricks very easily, and you can say exactly where they are. But in your guts, for instance, you're more likely to feel pain from stretch or twisting because our guts don't tend to have sharp things touching them. So the kind of pain we feel in different bits of our body depend on what those bits of body need to watch out for.

SKYLER: I never thought of that. When you've had a chronic pain from a medical condition that has now healed, why do you still feel the pain, sometimes?

DR. AMANDA WILLIAMS: That's a very important question and a very big one. It seems that pain itself changes your nervous system and makes it more and more likely to tell you about pain and even to feel things that used to be harmless like touch or warmth to feel those as pain. And it just seems that the nervous system gets stuck in that way of telling your brain what's going on and can't seem to get unstuck easily. It's very puzzling.

SKYLER: How do you help your nervous system get unstuck?

DR. AMANDA WILLIAMS: It's often about learning more about pain to understand that when you have chronic pain, it doesn't mean that damage is going on in your body, it's more a problem of the nervous system giving you the wrong messages. And then starting to do things again which feel like they might hurt, but doing them at a level that doesn't hurt too much and learning that the body is stronger and more able to do things than you thought.

And as people do that, it tends to make their lives richer. And that tends to mean the nervous system doesn't give so much space to pain because it's giving more space to nice things you're doing and friends you're seeing again and things you're planning and more confident of doing in the future.

SKYLER: Do different people feel pain differently?

DR. AMANDA WILLIAMS: Well, it's awfully difficult to know how someone else feels pain. We assume that we mean the same thing by the word "Pain," but when we do feel a pain, we bring to it our whole history, whether we've had that pain before or whether it's something completely new to us, how worried we tend to be, how vulnerable we feel in our bodies, whether we think that we're easily hurt and damaged or whether we feel we're quite strong and tough and can get through things.

And so somebody who, perhaps, has had a history of illness, a lot of treatments, doesn't feel very strong is going to likely feel more threatened by a new pain than somebody who is always getting knocked about in play or in sports and doesn't really bother because things get better on their own.

SKYLER: How much pain is in our minds? Can we just think our way out of pain?

DR. AMANDA WILLIAMS: We can think our way out of very, very mild pains if we're not at all worried about them, if it's the same old pain you've had before or something you're expecting. Like when you have a vaccination like for COVID, we tend not to think about the pain very much and not to feel it very badly. But you can't think your way out of bigger pains. And if you could just distract yourself from a serious pain, then you wouldn't be able to look after yourself.

MOLLY BLOOM: So you've been studying pain for a bit now. And I'm wondering, has our understanding of it or the way we think about it changed in that time? And if it has changed, how has it changed?

DR. AMANDA WILLIAMS: I think, in some ways, it has changed for the better. And Skyler asked about how the mind is involved. And I think there's better understanding now that pain isn't either in your body or it's in your mind, which most people would take to mean imaginary, but it's a combination of what happens in your body and what's happening in your mind. And your mind, of course, contains your whole history and your hopes for the future and all those sorts of things. So it's a very complex interaction that produces the pain. But I think there's better understanding of that now.

MOLLY BLOOM: That's really interesting.

SKYLER: Thanks for answering our questions, Dr. Amanda.

DR. AMANDA WILLIAMS: Thank you, Skyler. I really enjoyed being interviewed by you.

[MUSIC PLAYING]

MOLLY BLOOM: OK. Let's take a break and test your ears. Are you ready for the--

[MUSIC PLAYING]

SKYLER: Mystery Sound.

MOLLY BLOOM: Are you ready?

SKYLER: Yeah.

MOLLY BLOOM: Here it is.

[RUSTLING]

What do you think? Do you want to hear it again?

SKYLER: Yeah.

MOLLY BLOOM: OK.

[RUSTLING]

What do you think, Skyler? What are your guesses?

SKYLER: I don't know. It-- there's definitely like grass involved. And I think I heard someone running but there's also that thumping sound.

MOLLY BLOOM: OK, so there's grass, running, thumping. Can you think of something that includes all three of those things?

SKYLER: Maybe someone like has a ball that they're bouncing. I mean, grass doesn't bounce very well but maybe a really bouncy ball.

MOLLY BLOOM: I love that. Wonderful guess. We're going to hear it again at the end of the show. You'll get another chance to guess, and we'll hear the answer. So stick around.

[MUSIC PLAYING]

We are cooking up an episode about expiration dates, those little warnings you see on food packaging that tell you whether food is fresh or not. We thought it would be handy if our food could just tell us when it's gone bad, so we want you to come up with an alarm sound for rotten fare, maybe the sour milk in the back of your fridge would go, I'm stinky, I'm stinky, or your rotten potato salad would say, pot-ta-don't eat me. Skyler, what do you think food should say when it's spoiled?

SKYLER: Maybe like, eater, beware. Eater, beware.

MOLLY BLOOM: Oh, that's good. I would beware. Listeners, please record your rotten food alarm sounds and send them to us at brainson.org. And while you're there, you can send us mystery sounds, drawings, and questions.

SKYLER: Like this one.

CHILD 3: My question is, when your eyes are closed, are your pupils big or small?

MOLLY BLOOM: Again, that's brainson.org.

SKYLER: And keep listening.

MAN: (SINGING) Baba, baba, baba, ba, baba, ba Brains On.

SKYLER: You're listening to Brains On. I'm Skyler.

MOLLY BLOOM: And I'm Molly. Today, we're talking about how the pain medicine, ibuprofen, knows where to go in our bodies to help us feel better. So far, we've learned that we feel pain because of special nerve cells.

SKYLER: They spring into action and send a message to our brains when our bodies have been hurt in some way.

MOLLY BLOOM: But there's another step after these pain sensing nerves fire up. And it's super important for explaining how ibuprofen works. After you get hurt, your body sends these little workers called enzymes to the spot where you got hurt.

SKYLER: What do they do?

MOLLY BLOOM: Once the enzymes get to the pain spot, they make a special chemical that actually makes you feel more pain.

SKYLER: Rude.

MOLLY BLOOM: I know. But in theory, these chemicals are supposed to help. They're slowing the body down and swelling up the area that got hurt.

SKYLER: It's like the chemicals are saying, hey, don't touch this. It's healing.

MOLLY BLOOM: Exactly. It's like the chemicals are turning our pain volume up. But we don't like to feel more pain, so we take medicine like ibuprofen to turn the pain volume back down.

SKYLER: Cool. We haven't had ibuprofen forever, right? So how did scientists make it in the first place?

MOLLY BLOOM: Well, way before ibuprofen, humans used herbs and plants to help with pain. But one plant in particular was really important, the Willow tree. Ancient Egyptians and Sumerians first started using the bark of Willow trees to help with pain thousands of years ago. This plant actually helped inspire the first modern pain pill ever invented by humans, aspirin. But it took a long time for scientists to create aspirin and even longer to create ibuprofen.

SKYLER: How long is long?

MOLLY BLOOM: A long time. Scientists first invented aspirin over 100 years ago, but it had some side effects so scientists wanted something that would be easier on bodies. They tested hundreds and hundreds of different combinations of chemicals that didn't really work. And it wasn't until the 1960s when they finally figured out the formula for ibuprofen.

SKYLER: Wow. But I'm still wondering, how does ibuprofen know where to go to stop the pain in our body?

MOLLY BLOOM: To get that answer, let's go check out on ibuprofen's first day at work.

[MUSIC PLAYING]

PROFESSOR EN: Welcome to Pain, Pain, Go Away, your new employer. My name is Professor En, but you can call me Prof En, Get it? Prof En, like ibuprofen, anyone? Talents are wasted here.

Anyway, I will be leading your junior ibuprofen training today. Let's kick things off by reminding everyone how exactly we work to reduce pain.

IBUPROFEN IKE: I'm here. I'm here. Ibuprofen Ike, reporting for duty. Sorry, I accidentally went to the aspirin department and then got lost. It took like 50 years to get here. They should really put up more directions.

PROFESSOR EN: Hey, hey. Chill, pill. No worries. Just grab an orientation packet and take a seat.

IBUPROFEN IKE: Ooh, nice, a branded notebook and a USB stick.

PROFESSOR EN: Now as I was about to say, when a person gets hurt, they take us ibuprofen to feel better. Our job is to zip around the body and find those pesky enzymes that are making the chemicals that increase pain.

IBUPROFEN IKE: Find the enzymes. Got it.

PROFESSOR EN: And then once we find those enzymes, we just need to stick to them. That's our job. Once we stick to the enzymes, they can't make the pain chemicals. It's like magic.

IBUPROFEN IKE: Stick to those enzymes so they can't make more pain. OK. But how do we know where to go to find the pain spots?

PROFESSOR EN: Well, it starts when someone swallows us. First, we end up in the stomach, then we dissolve and we're absorbed up into the bloodstream. Then we can go everywhere. After about 30 minutes, we reach all parts of the body. Along the way, if we see the right enzymes, we stick to them.

IBUPROFEN IKE: Wait, you're saying that we don't need to know where to go? But I have a terrible sense of direction. Can I bring my phone to find the enzymes?

PROFESSOR EN: No, you don't need your phone. You just enter the bloodstream and go everywhere in the body. No directions needed. When you see the right enzymes, you stick to them.

IBUPROFEN IKE: What about my smartwatch? Just in case.

PROFESSOR EN: No, I'm saying, you don't need anything.

IBUPROFEN IKE: I'll just sketch out an enzymes map in this new notebook and bring that.

PROFESSOR EN: No. No, no, no. No.

IBUPROFEN IKE: Cool. OK. I'll just draw a map on a napkin to be safe.

MOLLY BLOOM: So ibuprofen knows where to go, by first going on a ride through our bloodstreams. Then when it comes across the special enzymes and sticks on to them, those enzymes are blocked from making the chemicals that cause us to have a fever, swelling, and feel more pain.

SKYLER: Exactly. Ibuprofen is throwing a block party, breaking up the pain, and making us feel better.

[MUSIC PLAYING]

When we get hurt, special nerve cells in our bodies send a signal up to our brain. And that makes us feel pain.

MOLLY BLOOM: And we're able to reduce some types of pain with medicines like ibuprofen.

SKYLER: Ibuprofen goes into our body and sticks to specific enzymes, blocking the chemicals that make us feel more pain.

MOLLY BLOOM: Even though ibuprofen doesn't know exactly where to go, it's able to travel through your whole body in less than 30 minutes.

SKYLER: It took a lot of work for scientists to invent ibuprofen. But since then, it's changed the world and helped us feel less pain.

MOLLY BLOOM: That's it for this episode of Brains On.

SKYLER: This episode was written by Nick Ryan and Molly Bloom. We had production help from Rosie DuPont, Anna Goldfield, Aron Woldeslassie, Anna Weigel, Nico Gonzalez Wisler, Ruby Guthrie, and Marc Sanchez.

MOLLY BLOOM: Our editors are Sanden Totten and Shahla Farzan. This episode was sound designed by Rachel Breeze. And we had engineering help from Alex Simpson and Luke Spicknall. Beth Perlman is our executive producer. The executives in charge of APM Studios are Chandra Kavati and Joanne Griffith. Special thanks to Melissa Chapman and Aidan and Zane for not making faces through the window at Skyler.

SKYLER: Brains On is a non-profit public radio program.

MOLLY BLOOM: There are lots of ways to support the show, subscribe to Brains On Universe on YouTube, where you can watch animated versions of some of your favorite episodes, or head to brainson.org, where you can sign up for our Smarty Pass. It gives you a ticket to special bonus stuff and ad-free episodes.

SKYLER: And while you're there, you can submit your questions and fan art.

MOLLY BLOOM: That's brainson.org. OK, Skyler, are you ready to hear that mystery sound again?

SKYLER: Yes.

MOLLY BLOOM: All right. Here it is.

[RUSTLING]

OK, so last time, you thought a bouncing ball. Somehow, grass was involved. What do you think now?

SKYLER: I don't know. It sounds like a basketball, but I know basketballs don't bounce on grass.

MOLLY BLOOM: OK. Any other thoughts?

SKYLER: The bouncing sounds like a pogo stick, but--

MOLLY BLOOM: I love a pogo stick. OK. So there's a grass. There's a ball. There's some sort of bouncing. Humans are involved, I'm guessing, in some way, unless it's a very talented animal, which would be cool. Are you ready for the answer?

SKYLER: Yes.

MOLLY BLOOM: OK. Here it is.

PAUL: Hello. My name is Paul from Arlington, Massachusetts. The sound you just heard was the sound of me juggling my soccer ball. And my brothers first taught me how to juggle and play soccer to begin with. And my record is 104.

MOLLY BLOOM: Oh, wow.

SKYLER: Wow. Juggling a soccer ball.

MOLLY BLOOM: OK, you were really close. There was definitely a ball bouncing. There was grass around. I am very impressed. And I'm also impressed, 104? Doing that 104 times in a row, I'm very, very impressed. Have you ever juggled a soccer ball before?

SKYLER: No. My big brother probably has.

MOLLY BLOOM: So juggling a soccer ball is when you kick it back and forth. And you keep it going until you stop. So you're not juggling it with your hands, you're juggling it with your feet.

SKYLER: OK.

MOLLY BLOOM: Does that make more sense?

SKYLER: Yes.

[RUSTLING]

MOLLY BLOOM: Now it's time for the Brains Honor Roll. These are the kids who keep the show going with their questions, ideas, mystery sounds, drawings, and high fives.

[MUSIC PLAYING]

[LISTING HONOR ROLL]

MAN: Brains On Live.

MOLLY BLOOM: We'll be back next week with an episode all about why we have expiration dates for food.

SKYLER: Thanks for listening.

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