Future Pharmaceuticals and Closing Thoughts

Welcome to the R of Science. I'm Hannah Fry And I'm Michael Stevenens. Okay, Michael, what's the worst pain you've ever been in? Oh goodness. I think it was when I was mowing a yard and a piece of sand scratched my cornea. O Yeah I mean, it was bearable. It wasn't like childbirth. you know, I'm not saying that. I'm just saying that I thought it would get better and it didn't all evening. So I had to go to the hospital and they like immediately put this special pain relieving eye drop in But that was bad. So as soon as you had the pain relief, it was kind of okay. Totally fine. It was so weird. In fact, the doctor wouldn't give me more to take home because he was like, peopleeople use this and then they can't even tell that their eyes are damaged And so it's like dangerous. Right. People do talk about childbirth being one of the most painful things you can experience, but it's not the most painful. What is the most painful Well, there is a condition which actually my ex husband had, which are known as suicide headaches. Oh, like the ice pick headaches.. I have heard that people who have given birth and had these kinds of headaches say the headaches are worse. Absolutely He had them. He had them. Yeahah. And when he would have them I mean, you really knew that he was in absolute agony. Essentially, the reason why they are called I mean, it's an awful awful phrase, but historically these things are so so catastrophically painful. It feels like a buildup of pressure in your head. But I think in particular it's the nerve in your face, the trigeminal nerve is really irritated, that's an understatement, is really under extreme pressure and pain when all of this is happening. And historically because there was no real access to pain relief, people would be in such excruciating pain that they would try and take their own lives just to escape it. Yeah, I mean, thankfully, that puts childbirth in perspective really, doesn't it? It is a bit annoying when you then go on to have children with people who suffer from suicide headaches because because sypathetic No sympathy whatsoever Okay, today, Michael, we're going to be talking about pain. I'm going to see your level of pain that you can tolerate. Yeah. We're going to talk about people who feel nothing and what that does to them. and we are going to talk about the underlying question under all of it, can we make the pain go away? This episode is brought to you by Cancer Research UK. Scientists have found that cancer risks usually increase with age and size, but some species defy the odds. For example, deep sea Greenland sharks. They can grow over six meters long. more than a small car and yet live for up to four hundred years. Now understanding how green and shhark's cellular repair and immune systems seem to have managed to keep them cancer free for centuries, that could open up exciting research pathways. Essentially over millions of years, evolution has been running the world's most successful cancer prevention trial. And sometimes breakthroughs can be found in unusual places So by exploring the unexpected, canancer Research UK scientists are uncovering new ways to tackle over two hundred types of cancer. Their work has helped to double survival in the UK over the last fifty years and continues to save and improve lives around the world. For more information about Cancer Research UK their research and breakthroughs and how you can support them, visit cancerreesearchuK. org slash the rest is science OkayK, Michael, I have asked you to prepare. something here. You've asked me to prepare, I've got a bowl of water here and I'm going to put ice in it. I've got the world's tiniest ice ay I'll all right. should be okay. I'll crack these in Oh yeah Okay, so what we're going to do in a moment is we're going to plunge our hands into these ice balls. I also have one here by the way, pre prepared. It's an opaque bowl, but you can just about see in the bottom. those of you who are watching there's I would say substantially more ice than in Michael's. Okay, yeah, I'm afraid I don't have enough ice. This is all I have. Yeah' be fine. It'll be fine. You'll look like absolute nails, Michaels. I'm gonna look so strong. I mean, we should let it cool down the water a bit. This was already very cold water. This is actually a standard way that researchers can measure pain thresholds in people Some people are much more able to sustain holding their hand in the sort of the extreme burning sensation that you get when your hand is in real cold. Incidentally actually, redheads, the research is developing here that redheads feel pain in a different way to other non mutants like yourself. I've heard that. I've heard that they don't feel pain. They have to be anesthetized differently. Yeah. But you're saying they feel it in a different way or just a different magnitude. Different magnitude. I think that they have a slightly higher tolerance to pain. Interesting. But takes more to knock them out. So we're gonna see, we're gonna both plunge our hands into this. while I tell you about the other experiments that they do to cause people pain. And we're gonna test, Michael. We're going to see who can hold in longer you or me before the pain gets to extreme Okay. All right, you ready? I'm ready Okay, let's do this. let's do this. Count me down. Oh, you're in. I mean, I mean Tracy one day. Okay, you've gone for a flat hand. I've gone for I'm maybe trying to cheat slightly by tucking my thumb in into a fist. but we'll see, it's already, I'll be honest, quite cold. Yeah. mine's cold. I should have more ice. It's okay. It' okay. This isn't scientific. This is just a little challenge. It is uncomfortable It is already uncomfortable for me too. I want to tell you though, while our hands are in here, you can hold it in for about three minutes or so before it really becomes absolutely unbearable. Also, be careful about doing this at home because you can genuinelyself give yourself ice burns. But the way that people use this in research around pain is that you establish an individual person's baseline And then what you can do is you can adapt it. So you can see, can they hold in their hand for longer when they're swearing, for example. The answer by the way, is yes. Yeah. Do they want to take their hand out earlier when they are feeling particularly stressed, for example? The answer is yes But researchers for a really long time have tried to come up with different ways to ethically subject people to pain. This is one of the kind of older, more traditional methods, but there is this new one that people are using, which I think is really interesting. It's something that was sort of discovered as a way to research pain by a guy called Fredrick Lindstadt. And what he was doing, he was at home He wondered what would happen if he got a pack of Frankfurters out of the fridge and took half the pack of Fank furs and microwaved them. and then left the others at a sort of you know quite cold temperature, sort of five degrees centigrade. And then he arranged them on a plate where it would be one at forty degrees, one at five degrees, one at forty one of five, one at forty one of five, sort of interchange them. and then laid a flat Tom across all of the frankfitters. Now I noticed you said, up when I mentioned this. Have you come across this before? Yeah, the thermal grill illusion. We did it with hot dogs on an episode of Minefield Okay. It's painful, and why don't you tell us why? How are you feeling right now, by the way, in the ice? I would say I'm enjoying the distraction of talking about hot dogs. Okay, we' keep going How you? Is it hurting y? It does hurt, but it's not bad enough. It's getting worse. I mean my ice is almost all melted already I've made it very easy for myself by just not being an ice man. You're gonna look like an absolute superhero. I would say I think the tucked thumb has definitely helped me here. Oh yeah. The outside of my hand is like is really especially if I concentrate on it, it's really, really burning a lot. And this is the thing, this is part of the reason why the Frankfurt thing ends up hurting because actually, really intense cold water, it doesn't register in your body as like very cold. It registers almost as burning. It sort of feels the same sensation as burning. And the reason is because it activates this pain pathway that your brain reads as a burning sensation. So your skin is effectively got two different receptors that are running up to the brain. One of them is like Cool reporter And this one says, okay, it's fine, there's nothing to worry about. It's not unbelievably cold, it's cool, so you don't need to worry about it. And then the other one is a burning alarm, right That's like, ouch, get this away. Suddenly my hand actually hurts way more when I' saying than burning. But cold can also trip this, right? So extreme hot or extreme cold will trip this sort of burning alarm So what happens with this illusion is that the warm hot dogs, the warm Frankfurters tell your brain, hey, look, this is definitely not cool because it's warm, right? It's not like if you just held the five degree Frankfurter, your brain would not trigger the burning alarm because it would say it's cool. so it's fine. It's no big deal, it's not super freezing But because the warm ones are there, they stop that trigger from happening. So your brain doesn't get the message that this is an okay temperature and so only burning sensation appears in your brain. If I explain that I mean, you give it a go, mayaybe you'll be able to explain it better to me. I haven't looked into this recently. I've heard that it's like you've got hot and cold receptors and obviously they don't go off together ever unless there is excruciating urgent pain And so if you can line the cold and warm hot dogs up close together in a line and put your hand or your arm on them, Your brain's getting a signal from both cold and warm receptors and that's only that only happens when you're like literally having your arm cut off. Yeah. It hurts so badly. And does it? Because I've never done it. doeses it really hurt? I actually did not do it. Oh and I regret this. We did it on Rosanna Pancina. We had her come on and she like couldn't keep her hand on it I don't know why I didn't try it. I think it's because I was the host and we were filming. But they have an apparatus at the exxploratorium in San Francisco that uses metal rods that are thinner and it's more effective. and I've always wanted to try that one I also want to build one and put it in the curiosity box so you can like hurt, Are you giving up? Yeah, do you know it's so strange because it's noticeable that when you are talking about excruciating pain, it furts so much more than when you're talking about, I don't know, like going to visit and explore trees and a fireplace, does that help you It does, it does. some like math to do, some just like algebra equations? I'm warm blooded for maths. Yes, I'm absolutely fine with it. do you know what I think I'm ging up. It's moving up my arm now. I' moving up my arm. I think I'm giving up I don't know how long I lasted. About three minutes, I reckon, probably. More than three minutes. It's least at least seven minutes. Oh, I can't feel my hand. M like maybe six minutes. That's good. I feel like this wasn't a fair test. My ice it's all melted by now. I have no ice left. So I've melted all that ice. You're just having a tepid bath. It's not tepid But I think that at this point, it's like maybe a one or a two out of ten pain wise. Right. Actually, I'm more uncomfortable from holding my hand in this position So I didn't do a good demonstration And I lost I lost my dozen ice cubes. So warm drinks for me today. I mean, I can keep my hand in just to prove myself, but there's no ice left. It's only gonna warm I think you can do the rest of this episode with dry hands. Okay it' coming out When we're in person, we'll perhap thermometers we'll do this with lots of ice, same temperature, and we'll really see who can take more pain. We'll see if the ginger really is talking a big game. I think if it felt more competitive as well, I think that that would sort of overtake I would want to stay in even longer. Here's the thing though, okay. So the reason why that sausage experiment is so interesting is that actually you're not in pain. you're not in danger. you're not hurting. You are perfectly safe. You could hold a forty degree hot dog and be fine. you can hold a five degree hot dog and be fine. What that demonstrates is that pain is not this faithful readout of damage It's a verdict that your brain is constructing and actually sometimes just plain wrong. Do you know where the word pain comes from, by the way? No, I don't. It goes back to Latin Unsurprisingly. Poina. which is Penalty or punishment Also in the Greek Pin which is blood money And it's sort of like the price that you pay for spilled blood. Right. But underneath all of it, it's like the root of the word pain is to pay to kind of aone. It's like pain is sort of a debt that you are paying Interesting. You know, my mother's maiden name was Payne. Oh, really? Now you guys can all steal my bank monies. Wait, Slled how? Spelled PA Y in E. Like Thomas Payne commommon sense. Anyway, so pain is a punishment, but nowadays it looks more like it's a A verdict, our brain comes I think that's a great word to use. verdict. It looks at the evidence and it just kind of has to come up with a decision and it might be wrong Even in other words that are to do with pain, like excruciating Excruciating has the word sort of crux as in the cross, right? Like the crucifix hidden inside it. Right. Oh wow, yeah I think that people have always filed pain under this idea of it being a curse or a sentence And now because as you say, actually We know that it's a verdict because we know that it's not sort of a direct reading of your environment In twenty twenty, the official definition of pain changed Pain is now defined as associated with or resembling That which is associated with actual or potential tissue damage And this is an important distinction because there are some people who actually have really serious chronic pain in their bodies without there being the tissue damage or the underlying physical cause that can be treated to cut the pain off. Yeah. My hand is still very cold. Yours must be so cold still. I was sitting on it and now I've got it in my Um, leg pit the other side of my knee. I don't know. what is that called Instead of an armpit. Yeah. The crook Of your arm, the crook of my leg, I'm like squeezing it See, look how hairy my legs are. That gives you a sense of how warm I am. all the times. Inulation all over the place. Right shouldall I give you some quick pain facts? Yeah, please do. So no seception is essentially your perception of pain. That's a great word, by the way no susception. Isn't it good? Is there any susception? No susception. There is none. None at all So noception, that's your sensory nervous system. It's the process of actually detecting An encoding pain stimuli and it's not the same thing as pain. Nosiceception is like the raw signal that is kind of traveling up the nerves and the pain is what your brain decides to do with it. A, it's the equalia of it all. Right, totally. because you can have the signal with no pain, right? Under anesthesia, b like cut wide open. these signals are definitely firing towards your brain, but you're not registering it. And you can have the reverse. you can have pain with no signal. So people who have had limbs amputated, for instance can end up feeling phantom pain for limbs that are no longer there. Right, right true. So the two things are not it's not like a one to one thing. But in terms of that signal, that nervous system signal that travels through your body, I'm sure that you will have noticed this just by like stubbing your toe. There are two different pain signals. If you hit your thumb with a hammer, For example, then you get like a very precise Jab,'s like outuch very quickly, like pull your hand away. sort of if you put your hand on a hot hob, for instance as well, that's the other one. incredibly quick signal that is going through these fibers that travel to your brain at twenty meters per second But the dull pain that you getess afterfter you pulled your hand away from being hit by hammer Or like if you stub your toe, for instance, these are your C fibers and they move at one meter per second. So actually I always think about when I stub my toe, I really notice this, stub my toe and then I sort of in my head I'm like one, two, there it is. And that's literally the pain signal physically traveling up your body and into your brain Yeah, it has a different speed. I made a a little YouTube short about the speed of pain. Both of these kinds of pain have their own purposes. That initial urgent fast pain is like move. It makes you move away or stop But then the slower throbbing pain that lasts longer is there to keep reminding you to tenderly treat the injured part of your body. Yeah, donon't ignore it. I tell you where you don't get those pain receptors, which is in your brain where the actual pain is constructed overall. Oh funny. Yeah. Even when you have a headache, it's not your brain that's hurting at all, it's sort of the surrounding of your brain. I mean, you see this with brain surgery. Yeah, right. So if someone said, I'm going to torture you by stabbing right where you feel pain you wouldn't feel it. You wouldn't feel it because there's no pain receptors in your brain. That is a weird thing, by the way, that I want to look into more. So first of all, we've all seen like, I don't know if, we all have, but open brain surgery is so weird because the person doesn't have to be under anesthesia There's like local anesthesia for where their skull has been cut in the flesh. But then you can just poke around, slice around, ask them like, okay, so can you still feel your fingers? And they're like, yeep, and they're like, o, guess you don't need that part of your brain I don't think that's exactly how it goes Surgery by visce What I That's how I would do it I wouldt use an Obsidian knife though, by the way. Yeah, thank you. That's a call out to a previous episode or an episode to come depending on the editor's schedules. I've always wondered about the feeling of mental exhaustion and what causes that. It's not pain It is a feeling we have where if you have been very focused for a long time, if you've been thinking a lot, you feel like you've used your head. Is that because you've actually been using your eyes a lot? What is that feeling? It's not pain. Our brains don't have nerves in them that give us feedback on like how it's doing. Is it hurting? So what's up with mental exhaustion as a feeling? So I don't know the answer to that for sure, right? And maybe there's going to be people in the comments who know way more about this than I do. But one thing I will say, have you ever come across the electrical current stimulators that you wear on your head? The EEG nets? No No, this is Oh with a stimulator. Yeahector. Okay, so here's this idea, right? is that actually what's going on in your head when you're thinking and actually when you're feeling pain, I mean, pretty much everything that you sort of sense in your body, what's happening is that charged particles are moving around. Sure ye. One of the theories, I guess is that exhaustion, but also things like depression are really amplified by there just not being enough charged particles in the right place. ye. So anyway, I have this thing, I have this headset that I wear sometimes. It sounds crazy, but it's actually it's FDA approved, it's used by the NHS And it just applies this very small electrical current on your head. And then suddenly your brain fog just goes away. likeike suddenly you actually Well, you got to show it to me. Where is it? Go get it. A I go to get it Yeah, a few moments later It's like this little headset Ah, okay. The thing is this is a medical device, right? You sort of have to do it under supervision of a doctor. So how did you get it? From a doctor? Right. Okaykay, so you said, hey, my charged particles just aren't fling chared particles aren't flowing, hit me up. And this has a bit of a reputation in these kind of things because you know, in the nineteen fiftty, sixty seventies electric shock therapy was really dramatic and I think quite unethical in a lot of the ways that they used it. But yeah, we were talking like really gentle and it's just about sort of so you get a little there's a slight difference in current between from one end to the other end, youve got an anode and a cathode. So how does it affect inside your skull? Is it like the electric Field Almost a magnet or I mean, essentially everything that's going on in your neurons is about charged particles moving from one place to another Right, Yeahah, squirting around different concentrations of sodium ions. Exactly. So what this thing does is it changes the resting membrane potential of the neurons Uuh Could it be dangerous if misused? I mean, probably. think like I think there's very good evidence about this thing. It's also by the way, an incredibly low electrical current. L you couldn't even feel it really if you put your fingers on it But the idea is that you just give your brain a bit of a head start and then over time, you sort of build new pathways. Okay, so you've had good results from it. Yeah, I really like it. I really like it. How often do you use it? Five times a week. Oh, wow, every day, except on the weekends where you just let your brain chill out. Ch out. deionize. Dionize What is it called? Transcraniial or direct current stimulation Oh, interesting. I've done transcranial magnetic stimulation on Minefield. Oh yeah in a lab where they try to change how your neurons are working, specifically in Brokca's area, just to demonstrate that they can stop you from being able to speak. And this also has a lot of therapeutic uses. So it sounds like what you have is a like at home version of that technology Here's the thing though, all thinking and feeling that's going on in your body is essentially these charged ions passing through different channels. I mean they're sort of sirting around your body, right? That's essentially what's happening. The way that pain works, we know this now, the way that you feel pain is that at the tip of every pain nerve is this little tiny gate that the ions sort of get squirted through, this little sodium channel. and it's called NV one point seven It might be that people call it NAV, but I'm going to call it now one point seven. So if that gate is open then the little ions get squirted through and gall up to your brain and you're like, U, I feel pain. ouch. But if that gate is blocked or sort of modified in some way that stops the ions being allowed to pass through Th you would feel No pain. You would still have sensation, you would still be able to like feel and touch things, but you would have no pain whatsoever. And it turns out that there is a gene It's called SCN nine A. There is a mutation in that gene. that marks up this particular little gate and means that there are some people who can feel no pain whatsoever Wow I've read fictional accounts of people with such a condition in the Flowers in the attttic series when I was a kid. rightight? There's a child in like the second books and on who doesn't feel pain. so always have to be so careful because this kid won't know if they've scratched themselves, they get an infection. won't know if they've broken a bone. I've met someone with this condition. Really? Yeah, he's called Stehen Pete. He is so amazing American guy has worked with researchers who are trying to like isolate this particular pathway, try and work out if there's different pain medication He was so amazing, but I have to confess to you, It's the only time I've ever interviewed someone where I had to pause the interview midway through to go and be sick I had to vomit because it was so horrific the stuff that he was telling me couldn't handle it, and I basically throw up in the middle of the interview. Oh wow. The only time I've ever actually felt really sick and I had to excuse myself was when I was at Berkeley looking at actual human brains. and I pretended like it was the formaldehyde smell that made me sick. And I'm like, I gotta go, I got too big of a whiff But really it was the idea that I was holding someone's identity. Like everythingvery they'd felt, every memory, every time they'd taken a child to the playground, it all happened in this organ that we don't understand. and I was holding it. We were just looking at it and I'm like, oh, my gosh, this is too too close to a human. So there's my admission that it wasn't the formaldehyde. Yeah, wow. you're right. It's incredibly professal. Okay, so his name is Stehven Pete. Stehven Pete, Yeahah. Talk about a Mondagreen. that also sounds like it's two people, Stehven Pete. It's two Stephen Pete. People do that to me, Michael Stevens and they're like,' is your name Steven or Michael? And I'm like, You can see there it says Steven Inns. No one's first name is Steven Inns. If my name was Michael Stehven, then maybe I'd get it. But this happens to me every time, not every time, a lot I think you're a better Michael than a Steve. If I had a son, I told my wife, I really wanted Steve Stevens. I did meet a guy whose name was Stehven Michaels. He's a brilliant musical performer. performed at my daughter's preschool years ago. and I'm like, dude, Stehven Michels, I gotta tell you, my name is Michael Stevens. And he was like, Ohh, that's neat Later And I was like, no,body wit, we' We're We're destined to be together. Where wouldd you go Oh, that's good. I like that. I have two friends, a gay couple who are both called Emma, which I really enjoy. And they've got a little daughter to the daughter. it's like, Ohh, what's your mummy called? Oh my mumy's called Emma. And my mumy's called Emma. I just really like that little. Oh wow, Yes. I think Michael Stevens and Stephen Michaels, you could have been the most beautiful gay romance story. That would have been so lovely. What would we have called our kid becausecause there's only those two permutations of two things. Yeah. I'll figure that out later. Anyway, okay, I'm going tell you some of the stuff that Stephven Pete told me, okay, but I'm editing this very heavily, obviously because I don't want you to throw up during this. First, I want to say Cycle Mevvens, that could work or then me? Maybe that one if we wind up having a second. I think you should have Stehven Stevens and Michael Michaels. That would be good, especially if they were twins. But how do you change the last name of your own child? Less you you want do everything you want. Well not everything you want. I've did a video on this. There are names that you aren't allowed You know what? funny enough, a name is a human right. The UN has said that a name is a right that you have as a human. So yeah, it's a human rights abuse to not name children Wow. Yeah, I mean, it's legal requirement, right?. Should I tell you some of the stuff that he told me? Because the thing is is that this whole idea of not feeling pain, especially if you live with chronic pain I think it feels like, oh, this would be such a blessing, but it is the most horrific curse, the most horrific curse. So they found out that he had this condition When he was a baby and he was teething, I mean as I was talking to him, I sort of noticed that his speech was impaired slightly. And basically what had happened when he was teething wasas he had bitten off a chunk of his own tongue And not even realized. They diagnosed him by holding an open flame underneath his foot and he didn't flinch. Like this is a little baby, right? Keing a toddler safe full stop is quite difficult, but like when they're not feeling pain, he would sort of use it as a way to get what he wanted. So if his parents, you, as a teenager were like, you need to do this, he'd be like, m and would sort of sit there and break his fingers just to Oh no, wow The mortality rate of people with this particular mutation is incredibly high. Lots of them die in childhood, particularly historically, and if not in their teenage years. It's really, really, really not nice. You know If you want real proof of the fact that not having any pain at all is like such a horrific curse leprosrosy, which people had historically thought was a condition which rotted flesh. Actually in the nineteen forties, there was a surgeon called Paul Brand who discovered that actually that's not what it is at all. All it does is a bacteria that kills the nerves So means that you cannot feel pain and thus it's your own actions effectively that mean that you lose toes, you lose fingers. These are self inflicted wounds that are unfelt, essentially. It's a really horrible story about him going to India to a leopard' colony to sort of study people and at nighttime, he would have to stay up to sort of fight The rats away from kind of chewing on people who were asleep because they just couldn't feel it. they couldn't feel the pain. Wh, I didn't know that about leprosy.. I know that there's like wet and dry leprosy, or at least that's what they were called back at the time of Papillion Have you ever seen that movie? No. There's a really cool scene where Papillion, an escaped prisoner is trying to find a safe harbor and he comes to a leopard colony and they're going to kick him out and they're like, we'll let you stay if you smoke for my cigar So the idea is like, oh, it's contagious. he's going but he grabs a cigar anyway and he smokes from it. and gives it back. And the guy goes, how did you know that I didn't have contagious wet leprosy? And Papillon goes, I didn't. I'm just that des It's worth a gambble for you to protect me. Yeah, it's a very cool scene So hold on, wet leprosy is contagious and dry as not. That's at least what I learned from the movie. and I have not looked deeper into it, but I do think it is true that there is a contagious and non contagious version But I mean, it's a bacteria that causes it so presumably, I mean, it's not a particularly prevalent disease, at least in the western world now, right? It's not something that you have to particularly be concerned about. Yeah, I haven't run into it. Oh, you're right Yeah, nerve damage may result in the loss of nosaceception There you go Let me just look up contagiousness. Okay, so all I'm seeing here is that leprosy is not highly contagious They can live with their families and attend school and work. This is right from Wikipedia So I don't know if there's two different kinds. All I know is that In the movie Paton and maybe also documentary It was supposed to be a bit of a documentary. It's based on the guy's life story that he wrote. but anyway pain So I didn't know leprosy was related to the loss of no sception. I mean, the main thing that I know about leprosy is from being a Catholic, right? Be Boy do they talkking about it a lot in the Bible? A lot of people get it Yeah. A lot of people get it in the Bible. There's something really interesting here, which is that when you look at the origin of the word pain, it's like a curse. but actually the real curse is not having it at all. Yeah The sort of perception of what pain is and what it is kind of doing for us, notot only that has changed, but like how you could measure it itself Because there have been people who've been like, right, well, let's just create a scale here. Let's just create numbers where ten means something, a particular type of pain and then we just be able to everyone would be able to scale it, right? So there was the dollarimeter whichich is a lamp that would focus on a sort of blackened patch of forehead. And then the idea was that there would be like a unit of agony, the doll scale n to ten point five, which is I think, frankly upsetting that they go to ten point five. But at eight dolls, it would leave second degree burns on the skin But it was just a bit all over the place. and what they tried to do, they tried to calibrate this with different people. They would go in when people were in labour, when women were in labour, they would go in an in between contractions. they would try and like burn their hands. Oh and ask how it compared. It's like, well, what hurts more? This or the actual childb. How many dolls are you feeling right now? How many dolls? And I'm quotly here, one subject became so hostile whichich you would, but they abandoned her. Anyway, the point is they tried this, right? But the numbers never reproduced. They couldn't find, they couldn't manage to extract like a certain level of heat that then correlates to a certain number on the scale No, it would depend way too much on the set and setting You know, like like we've said, if someone was more stressed, they're going to feel it differently than if they're focused or or chill It's going to matter whether their hair is red or not apparently. Right. But the point that you just made about How you're feeling being such this integral key part of it. It is As it turns out, almost all of the story is what's going on in your head. There was like some early indications of this when people were studying this, particularly during war settings, right? So like in World War two, there would be soldiers who had these catastrophic wounds who are kind of getting up and walking around and like apparently feeling nothing. And there is actually a physical mechanism that can cause that there is this kind of descending control system. So it's not that you just have pain happens here, it goes straight to your brain. Actually, you kind of have this gateway through the spinal cord. and what can happen is your body can effectively like close the gates in the spinal cord before you've ever actually felt anything. This by the way, is one of the reasons why if you have a kid who falls over and then you're like, Oh, rub your knee. R? You can actually help because if you have like a harmless touch, then it can help to confuse the signal and basically stop it reaching your brain. It kind of closes the gate when it gets to your spinal column. That makes sense. But there is some amazing research in Oxford University by Irene Tracy, who I've gone to go and meet. She's amazing, by the way. She's known as the Queen of Pain. What a title. What a great title. She has this lab which she cheerfully calls the torture Chamber She has different ethical ways in which to inflict pain on people So she stabs people with needles, she burns them with like chili pepper on the skin. It's like cutting, burning, what the other ones, stinging Thrermmal grilling? Thrmal grilling. She doesn't thermal grill, or at least I didn't see her thermal grill I think she was actually just causing genuine pain. But she does this to people when they are inside of an MRI scanner Hm. And what they can do is they can inflict a kind of discrete Measurable amount of pain with these needles that have like particular pressure. So you know that the physical sensation Or at least the cause of the physical sensation is kind of very well controlled between people And then you can see how people construct or react to that sensation in their brains depending on what particular state they're in And you're absolutely right that basically, the more stressed you are The worse it is, the more relaxed you are, the easier it is. The more that you've had experience of pain in the past, the easier it is, the more that you think that the pain signifies something dangerous, the worse that it is. Yeah. But like all of these things end up really contributing to your experience of what is actually going on Yeah, if I am worried about it, I'm going to think about it a lot more. which also might explain why kids can be so much more affected by what seems like it shouldn't hurt as much as they're acting. But I mean, it's the first time they've felt that And they're so powerless, like of course, this is a big deal. And it also makes sense how your pain will lessen when help arrives because you no longer need to be as careful or cry out for help. It's arrived. It's not necessarily a placebo effect. It's just a straight up your body going, okay Phase one is over, now we'll begin phase two It is just a straight up actually, it's okay, you're safe. Yeah. There was one thing that I used to do with my little girls when they were really young. I tried to teach them that when they would fall over to immediately do jazz hands Oh I like to sort of make it into a happy moment because I think that they really feed off of your reaction to something. I think if you are like, oh no, this is serious Then it's like the panic arises and all of a sudden it becomes a really, really big deal. Whereas if you are like happy and clappy and it's like, hey, no big deal. there's crack on. we're still playing. It's not just that they ignore the pain, it's that the actual pain that they feel is lower. That's right. I think that's really it here. We're not talking about placebo. I mean, placebo feeds into this a little bit in the sense that you're tapping into the same thing. But what we're really talking about here is you actually feel it differently. Like your physical sensation is different depending on how you're feeling So is there a way to measure pain at all I mean, I know we have those like scale of one to ten, you know, point to the smiley face, which one are you I guess that works because it's a subjective thing, but we can't build a payanometer lug it into your brain and go or plug it into your nerves and go, ah nah, there's no pain. In the same way that we can't build a delicious ometer. Right? Or like a happy ometer. A loometer. Which of your cats do you love more? We're gonna find out today using our lovevometer. It never goes wrong. Yeah It doesn't work. It doesn't work. I mean at the same time, we do know lots of things about it. L we know that your belief changes it, but we also know that your memory about it afterwards changes. True. We know that you don't store it as like a running total. you store it as like a peak and the end This is some Carniman work. he was researching colonoscopies. Colonoscopies is not very nice. They're not very comfortable. I forortunately never had one, but you know my understanding is that it's just not a very nice experience to be part of. But they were talking about people's perception of the pain when the probe was removed immediately afterwards or when the probe was really slowly removed and then sort of paused before the final removal. And actually, even though the whole process was lengthened, it was a longer period of time with the gentle removal, people's memory of the colonoscopy was that it was less painful when the ending wasn't so bad. Right, of course. Yeah. when I'm thinking of times I've been in pain, Don't remember the middle of it I remember like how it started it after But yeah, that's interesting. The way I remember my pain is not the way I remember a movie? No, it's not. It's the peak and the end. that's essentially what you remember. The thing about this idea that your brain is giving you kind of free analgesia, right? I think there's something really extraordinary in them because I think for the last one hundred and fifty years or so what science has done in the pursuit of mitigating pain has been Okay, take this drug, you know we'll compare it against the placebo, but let's see how much extra this drug gives you compared to placebo. And kind of all of the focus has been on that And in a lot of ways, I feel like we're sort of thrown away the half or maybe more that actually makes a really gigantic difference, which is out much more w woo I'll admit, you know, it's much more sort of like softly, softly, like huggy feelings It's also the bit that doesn't come with any side effects. Yeah. It's woo woo adjacent, and I'm glad that we're taking it more and more seriously. because here's something weird I heard when I was at McGill University. Aeda to medifine In America, what we call Tylenol, especially Tylenol Paretamol in the UK, we call it R So since Tylenol entered the market It has become more effective. reducing pain As a pain reliever, it's gotten better The chemical formula has not changed. So there's this open question, what's happening? Are our bodies changing? Have we evolved to work better with Tylenol? The best answer seems to be that no, we just trust that it will help the pain more now When it was first introduced, people thought, I don't know Now we just go right to the Tylenol, you take it and you feel better because your brain goes, it's gonna work. Yeah. So the placebo effect has become more powerful. I think that we can do a whole other episode on the placebo effect specifically, but it's more than just the sort of illusion as it were of like feeling like you're being cured. This is Actual phhysiological facts, right? which is that pain is not a deterministic thing It is a sensation that is constructed by your brain subject to your entire experience Yeah, I do sort of think we've been kind of ignoring that a little bit. As I've mentioned on this show before, I had cancer a few years ago. and I always think that actually the doctors might have cured me, but the nurses made me better. Oh, interesting. And I think that is it, right? Like the nurses were the ones who actually made me feel like it was gonna to be okay You know, they were the ones who were there Like with the tea and sympathy. They were the ones who were like calmly and carefully helping me through the process of like removing all the tubes and you know, all of this stuff. And I think that what they were doing, a really, really good nurse is one who knows how to tap into your brain's free analgesia. They do. That's what makes them good nurses I think that effect extends to all kinds of other professions. I feel like physics keeps me safe on an airplane. Yeah. But the flight attendants make me feel safe I know. plane can deal with this amount of turbulence. but when I look at the flight attendants and they're like not even paying attention to it, they're just doing their own thing, looking annoyed or whatever. I'm like, thank goodness. I'm so much less worried because you are I'm like marrying your behavior. Pain is definitely a social phenomenon phenomenon of the mind and not just the brain Totally agree. At the same time, the last thing I want to tell you about is so I guess there's like the different places to target pain. And and as I said, if you are someone who suffers from chronic pain, it's like, well, that's very good, but you know, I can't just like wish myself better. And I agree. It's like it's really, really difficult to do this. You do also want sort of effective pharmaceuticals And the thing about like all of the stuff that we have really, you, opioids being the most effective at blocking the pain, it kind of like blocks everything else as well. You can't really function. you it's not specific enough. But going back to that NV one point seven, the little gate that allows all of this irons through. So there is some work that is going on now which is, okay, well, is there a way that you could design a drug or maybe genetically engineer your neurons or is there something that you could do that targets that channel in particular, right? That little gateway in particular. Because actually the other way round, it does happen. so you know the bullet ant donon't. No. Okay, so this is supposedly, I mean, there's like some crazy scientist Justin Schmidt was one in particular who deliberately go out and get themselves stung by absolutely everything in order to rank He writes like Semelier like notes for different things. So he says something called yellow yellow jacket wasp. It's sort of hot and smoky but almost irreverent in the feeling that it gives me, okay? Oh I love that. Yeah. But the bullet ant is like topop dog in terms of how much it hurts. He describes it as a flaming charcoal with a three inch rusty nail in your heel burning for twenty four hours. Okaykay. Now the reason why bullet ant wins in terms of pain is because it's venom actually attacks Nav one point seven, like the same channel. Yeah. And so what it does is it just jams the gate open effectively so that your pain nerves just fire over and over and over and over and over and over and over again and won't switch off. You're doing the exact opposite of what happens with the people who feel no pain whatsoever. This gate is like wide open as opposed to completely closed But yet the bullet ant Bite is not probably any more dangerous than a black widow which might not hurt nearly as much and yet is so much more potentially lethal. Right, just because of this very particular sort of biological formulation And so the question is, can you do something that directly targets that Nav one point seven? And some people have tried, right? They tried, they tried. I definitely shouldn't laugh about this because it would be amazing if you could. There are different drugs that people have constructed And there was one of them that actually looked like it was going to be really promising that would Target Nav one point seven would close that channel and then you could choose to turn on and off pain. Unfortunately NAavV one point seven is also really close in design in sort of the way it's structured to NV one point five, which is absolutely critical to maintaining a heartbeat. Oh my gos. So if you get even slightly bit wrong, you just start end up closing the pathways that closing these gates that allow your heart to beat. That's unfortunate That is unfortunate All the same, I think as we are getting further and further into really amazing molecular biology design, sort of synthetic biology, This is, I think, the hope, right is that there will come a point in the future where we can create something that allows you on demand to take some kind of pharmaceutical that just switches off that NV one point seven when you need it and not when you don't. Right. So this could have less addictive potential than opioids. could help people with chronic pain as well. Exactly. But There's always the balance of you need some pain. You need to know what's going on with your body When it's not helpful, it's not helpful. Exactly Okay, so I guess to sum this up then, pain isn't this payment, right? The word says that it's a punishment, but the actual mechanism itself is, I think more of a gift, actually. this verdict that your brain is creating, this kind of call, this decision that is being made on your behalf. And honestly, mostly in your favour. It's just unfortunate that for some people that message keeps on keepeps on blaring even when Yeah But its intentions are good. Its intentions are good. But we know what's paved with good intentions. so Very true, the road to hell. Okay, I guess that brings us to the end of this episode of the Rest of Science. Thank you very much for staying with us all to this, but look at you guys, look at you go. You're the real ones, you know? They're painless, aren't real geez. Yeah Thanks for listening. We really appreciate all of your support and especially your questions Please keep them coming in The rest is science at goalhanger. com. See you next time