There is a place in the UK where scientists can do something rather unusual. We've got a toolkit here that we're going to use here. Researchers are legally allowed to hurt you deliberately, deliberately induce pain. The goal: to decrypt the complexities of one of life's most important experiences. How are you feeling in there? Okay, to better measure and manage it. Okay, SC starting and potentially one day even Master it. Oh wow, I'm Professor Hannah Fry, mathematician and writer. I want to explore how modern science is changing our fundamental understanding of pain for real. That is extraordinary, and whether a pain-free future could ever be a reality. 30-year-old Amy Paul never intended to become a TikTok star, but she started creating videos and found success. [Music] Hi, hello, I think. Sorry, he's very excited. Name 5 and a half years ago. I was living my dream as a primary school teacher. Then I got sick, very sick. Is that your hand over there? Well, it was my hand. Yeah, yeah, I took a cast.

of it before I had surgery. I had surgery to take off some of the attendance. You can see it if you want. In 2017, Amy suffered a medical complication that led to her hand becoming severely infected. It just kept getting worse and worse, and it was so painful, and the infection just wouldn't go. So, it started to look like, oh my wow. It's really hard to describe, but it felt like my hand was going through like a meat processor, like constantly. The doctor that was treating me then diagnosed me with something called complex pain syndrome (CRPS), and I had no idea what it was. CRPS is a poorly understood neurological condition resulting in severe and debilitating pain. To cope, Amy was prescribed a variety of pain-killing medications, including opioids. Those things are quite hard to come off of if you're in a really, really strong pain condition. Yeah, I've been through withdrawal from coming off them, and some of them afterwards, I was like, 'I don't even think that was doing

anything 'cause I still feel the [Music] same. Although pain is a personal experience, suffering from chronic pain can affect loved ones too. My daughter's life was just falling apart, and to see a strong woman who had, you know, she had ambitions for life, she was full of life, to then be reduced to somebody that just lived in constant pain. But as a mom, I wanted to help her, and I wanted to take the pain away, and you just couldn't. There was nothing, nothing that I could [Music] do. If we just get all the way down here, come here, let me help you. Where the sand, the sand is wet, it will be a lot easier to drive. What a beautiful bit alongside. Amy uses a number of treatments like hot wax therapy and a neuros stimulator machine to help cope with her chronic version. So it sends signals up the muscle and out this pad, and it makes things move, boom. There may not be a cure, but amidst it all, Amy has found a way to keep going. How did the Tik Tok stuff start? Oh my so

I was in quarantine for 2 weeks, and I knew this app, and I was like, Oh, I just make some videos. And then people started seeing it, and it grew, and it grew, and it grew, and it kind of became something like therapy to me. Of all of the things that you've tried, what do you think's made the biggest difference? I think just my mindset, to be honest. I always say, like, Stop fighting yourself, stop fighting for yourself, because instead of sitting in bed and blaming myself or doing things that could harm myself, instead, I could go out and live. It's just such an extraordinary story. She's in constant excruciating pain, and the best that medicine can offer her is just some drugs to sort of numb the pain, just take the edge off. We don't have anything that really gets to the heart of what pain is, what causes it, and how you can stop chronic pain when it's got to the point that it completely ruins your life. It is for this reason that

Scientists today are researching the fundamental mechanisms of pain to understand how it works inside our body. If something hurts you, something that burns, or something sharp, it activates pain signaling nerves called nociceptors. Now, you'll find these all around the body. They're in your muscles, they're in your joints, and crucially, they are just beneath the surface of your skin. And when they're triggered, a message gets sent up swiftly to your brain. That signal is going to tell your brain where your hurts and how bad it is. And then it's in the brain that's all compiled, and pain emerges as something you actually feel. But here's the thing: our brain doesn't just take those pain signals and do a simple sum about how much it hurts. It actually plugs them into a sort of model that our brain builds, along with a host of other stuff, weighing up things like our memories of pain, our expectation about how much something should hurt, whether you're paying attention or distracted, even your beliefs of whether you deserve it or not.

our brain juggles all of that to come up with a singular feeling, a perception of pain that is completely personal, private, and subjective to each of us. And that means that where some people can end up living a life full of pain, there are others with an extremely rare condition who have the exact opposite experience. How did your parents find out that you don't feel pain? Uh, so what happened was I was teething, uh, so I was an infant, and I ended up chewing a good portion of the tip of my tongue off. But... and you didn't know you couldn't feel it? No, they immediately took me to the pediatrician. Um, the way they found out that I didn't feel pain was by putting a flame underneath my foot, and uh, I didn't elicit a painful response. So then, if you're a young boy and you don't feel pain, what does that actually mean? Like, how does it change your life? So with myself, um, I I was kind of like the Daredevil. There was one time I was on a swing and

I was going way too high, and I jumped. When I jumped off, I landed improperly. Couldn't move. My movement was impaired because of my broken leg. For people with a genetic condition like Steve, pain never reaches the brain. Normally, a pain signal is triggered when charged ions pass through specific proteins in a neuron. In Steve, one of these proteins is faulty, which means no pain signal ever leaves the site of the trauma. The discovery of this mutation has opened up possibilities of new treatments for chronic pain. Not only does it give them the opportunity to learn more about pain itself, but it also gives them a little bit more insight into how those genes play a big role in that, with the hope that one day they can reproduce it using medicine. I guess yes, yeah, yes, that's the end. [Music] Call if Steven's condition holds the clue. If a single protein is so important to the body ever sending a pain signal, then controlling this protein would be a huge step towards a new approach to

managing pain. This is precisely the goal of Professor David Bennet and his team at the University of Oxford. Oh wow, it's really beautiful. We don't want to get rid of all pain, actually. We would need some pain perception to be left; otherwise, I think we would develop some of these nasty injuries: multiple broken bones, tissue injuries. Steve can't transmit those electrical signals that need to carry that information to the spinal cord and the central nervous system. So, of course, that's been phenomenally important for us to understand. Fun kind of how one, just one single protein can have such a fundamental effect on pain perception. Pain feels like it's all-encompassing, right? It's like every element of your body, you know, tips of your fingers down to your toes. And then once it actually comes down to it, you're talking tiny, tiny molecules. You're talking basically at the level of atoms and chemistry, absolutely a tiny, tiny protein. It's a really important target for us to think about coming to develop drugs to try and block that.

protein. The team can alter the genetic code of a single neuron, giving them the power to stop the pain signals. Not altogether, only when they add in a specific drug, essentially allowing them to crank up or dial down the pain signal at will. Does it actually work though? It works. The fundamental principles work now extremely well, and they can give you exquisite control, and hopefully, we'll show you some examples today. The first step is preparing the neuron, which involves some extremely precise microsurgery to insert an electrode. We want to record this electrical activity, so what Steve is going to do is we have a very thin micropipette, which is acting as our electrode, and he needs to approach that neuron. Basically going to inject a single neuron. Is that what we're talking about? Yeah, so I have to get very, very close. How steady is your hand? Thankfully, this does it for me. Okay, all right. I'm blown away. Across the lab, another neuron is ready to go, behaving as expected and producing

a steady electrical signal. Each one of these vertical lines here is an electrical pulse. But as soon as they add the drug, the neuron ceases to be able to fire. What's happened now is Kina has added the drug to activate this receptor. You're turning this off. Turn it off. You can see it happen in real time. It's getting smaller and smaller and smaller and smaller and smaller. So if this happened to be in someone's body, it would be they would be feeling the pain declining. Yes, what we're saying is a really important driver of pain is this activity within human sensory neurons. And this is a technique by which we can turn it off, actually happening in front of you. Oh my goodness me, it's in a Petri dish now. But the hope is that this treatment will eventually be trialed in patients and a new drug will be able to control the sensation of pain. You know, I think sometimes it's worth taking stock of exactly where we are with science now because what those

guys are doing. They've worked out how to inject a message into a single neuron that allows them to switch it on and off at will, like they have some sort of remote control. I mean, that's not even the whole story about pain. All they're doing, all they're doing, is just stopping the message being sent up from your extremities when you feel something. But there's a whole other section of this message getting into your brain and you constructing a feeling about that sensation, and these guys aren't even looking at any of that part. You've got this representation of the body on what we call the sensory cortex, which when it comes to the question of how our brain perceives pain, there's only one person to talk to. So, going from the bottom of the brain up, like a loaf of bread, yeah, and then you got the white matter which sends all the information around the brain is dark. Professor Irene Tracy pioneered new ways to study pain perception, earning her the slightly ominous title queen of pain. So

What we're looking at here is the normal response of a healthy physiological system to something that is painful. You can see these red blobs, and those red blobs tell us where the brain has become active in response to that sharp poke, that mechanical pain. With a few sharp prods and a high-powered MRI scanner, the team can begin to reveal the fingerprint of this once subjective experience. So, seeing pain like this brought a sort of objective piece of scientific data to map onto what the person is telling you, and it can help explain why somebody experiences something more painful than somebody else. So, I guess you see these patterns in general, but these results are perfectly specific to him and him alone. Exactly, and we know that the variance of how people will rate that pain, even to the same stimulus, is a combination of their genetics, their upbringing, using a precisely measured poke, and the chemical responsible for the burn in Chile. Irene and her team can illustrate just how malleable and complex our brain's response to pain can be. He's putting a good dollar for that.

on. It's been soaking in, and then when he pokes again, not in the area where the cream has been, but outside, even though that area outside is normal skin. When it hits the spinal cord, those mechanisms are going to turn up the volume, literally, and send more signals into the brain so that will hurt more, and we'll see more brain activity. Even though the poke was the same, the brain has the ability to give more importance to the incoming sensory signals, making it hurt more all by itself. And this personal experience can be shaped in unexpected ways. So, if pain is perception, then does that mean that you can change it? So, we've done experiments to make people deliberately anxious in the scanner, less anxious, happy, sad, and it changes the physiology. A depressed brain will amplify the signals a lot more than a non-depressed brain. So, when you go to the dentist and you're a bit anxious and nervous, you will feel pain more. It's not just your mind playing tricks; it's your brain is physiologically through anxiety.

turning up the volume when those signals hit the brain. So then we can have a more mature conversation about how important some of these other mechanisms are in chronic pain patients and how we must treat them in addition to obviously trying to just calm down where the injury is or the problem that's initiating the signals going into the brain in the first place. I got to go meet a patient who has CRPS. Oh, that's an awful condition, really horrendous chronic pain. She said that the way that she's learned to manage it is by doing things that she enjoys, by social connection. At the time, I sort of thought, Okay, you know, I mean good for you, it's a little bit wishy-washy, but the way you're describing it is that that's actually has a mechanistic thing. Body until we got all these wonderful new therapies, you know, it is pretty bleep for patients, and these are not wishy-washy. Your brain is incredibly powerful, and it can make it much worse.

or you can help make it not at least much worse and hopefully a little bit better. If you are happy and you're less anxious, lights are down, it's karma. If you are anxious and depressed, lights of firecrackers inside the brain because your body has the ability to tweak the dials, but you've got to work with them exactly and get them to start to harness some of those networks that's going to produce that sort of free analgesia, I call it. If our lived experience changes our perception of pain, then has Western medicine been missing something by focusing so heavily on pain medication alone? When you see what's going on inside somebody's brain, it's not an on-off switch, it's a volume dial, and that makes it so much more complicated. And then the whole thing about chronic pain is it's when that's turned up in a way that no longer serves you, and it sort of feels like the answer to turn it down again. I mean, it sounds wishy-washy, but

it kind of comes from within. This is getting very close to ancient wisdom for my liking. The practice of using the power within our bodies to master pain is something people have been doing for centuries. In the West, perhaps with our focus elsewhere, we've maybe lost our connection to that. But in many countries today, the combination of modern pain medicine and more traditional practice is alive and well. How are you doing? I'm just so curious. I kind of want to ask like everything. What are the big ones? Singapore's health system uses both eastern and western treatments to combat pain. Step One: shift body weight to the left and push forward. Rheumatology Professor La Tang Ching, who teaches medical students, is an advocate for using both approaches. [Music] You're in sort of a unique position with this, the kind of Western medicine on the one hand and then the traditional Chinese medicine on the other. Are those two things in conflict with one another? In Singapore, we actually have some Western doctors who are trained in both, especially in acupuncture, and what we have been

advised to do is to have two Frontage, so the patient can either come to you to seek Western medicine, or they can come to another door or another clinic to be looked after in the acupuncturist or a traditional Chinese medicine approach. Are there situations with pain specifically where you think that actually traditional Chinese medicine has got a real head start on Western medicine? There are some conditions the Western medicine may not have a diagnosis for. You have this headache that nobody can say what the cause is. You can see that some part is imbalance, and then we actually do have some sometimes a TCM angle to help to balance the different things. So, if I were to say that this person is brought up in a traditional Chinese medicine-friendly environment, the person will have the faith that it is going to help, and therefore the chance of it working is actually a bit better. So, that is a little bit of placebo effect, but I think placebo effect when work in the correct way is actually very beneficial. Yeah, the placebo effect, maybe science has sort of thought of it as like this

you know, kind of thing that you can measure, but we can't really explain that. It's like, it's the sort of ability of your body to, I don't know, empower itself. Professor Lao tries to tailor pain treatments to a patient's individual beliefs, but he's also more generally a firm believer in an open-minded approach to care. There's enough evidence to show that when you have chronic pain, it becomes emotionally, spiritually intertwined. In the wisdom of the ancient people, they realize that all these are intertwined into the health of an individual. Although they don't know how it works, but they know it's important. So, Western medicine is probably coming back to that sort of holistic approach, but we may have to systematize it in a different way. And that's why we, it takes us a bit of wisdom to sometimes stop and reflect, and maybe look at what is really good even in the past and still keep it. Do you think that Western medicine got a little bit maybe

sidetracked for a couple of hundred years. I mean, they've done the sort of like physical interventions, pharmaceutical interventions very well. Yeah, but it almost seems to me as though, I don't know, maybe something about the traditional approach has kind of been a bit forgotten or overlooked. Actually, when we first train as doctors, we are always reminded to look at a person as a whole. There's a famous thing to cure sometimes, to relieve often, and to comfort always. And many of us still firmly believe in that, but it's just that in the busyness of things, we take sometimes, we have to take shortcuts, and then we have to compartmentalize our roles. The Comfort always shouldn't be a bracket at the end. Yes, it should be like a really important part of the sentence. Yeah, Comfort is actually always possible, and comfort actually can relieve and sometimes even cure. When it comes to living with chronic pain, there are more methods of coping than those routinely offered by Western doctors, and these are tools that have

already existed did for centuries. So, I've actually spent quite a chunk of time in the hospital, and when I was there, I joked that the doctors might have fixed me, but it was the nurses who made me better. And now I think there might really be something kind of profound in that idea because, okay, for me, it was the nurses. For Amy, it's finding a sense of purpose. And maybe for people here, it's some kind of alternative medicine. But you know, all of those, they're all accessing the exact same principle, which is harnessing the power of the mind to change the perception of pain in the body and then actually make you feel better. Of course, pharmaceutical interventions are really important. There's big scientific breakthroughs that you cannot forget. But when it comes to controlling our pain, I think that science has made a mistake here. I think that we have been maybe too skeptical about this other phenomenally powerful idea. [Music] [Music]

What If Pain Could Be Made Optional? | The Future With Hannah Fry

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