How does pain work? Dr. Sanjay Gupta Explains | Fresh Air

What this episode is about

Dr. Sanjay Gupta discusses the complexities of pain, exploring its causes, potential relief methods, and the available insights that could change public understanding, as detailed in his book "It Doesn't Have to Hurt." He emphasizes the ongoing advancements in pain management and the importance of making this knowledge accessible to the wider community.

Key takeaways

• Pain isn’t just a symptom; it's a narrative your brain decides to tell, sometimes inaccurately.
• Your brain's like a social media feed: it prioritizes pain signals, amplifying some while ignoring others.
• Phantom limb pain proves the brain can craft agony even for something that’s physically absent—talk about a haunting!
• Referring pain? The brain's version of playing telephone: what hurts isn't always where you think it is.
• Unlocking pain mysteries can revolutionize treatment; Gupta's mission is to turn medical insights into public knowledge.

Who speaks in this episode?

• Terry Gross (Host) · 15 min speaking
• Dr. Sanjay Gupta (Guest) · 23 min speaking

What is discussed, and when

1. 0:00 – 5:00: It Doesn't Have to Hurt, Emory University Hospital, CNN's Peabody Award
2. 20:00 – 25:00: Motrin
3. 25:00 – 30:00: Susetrogene

Notable quotes from "How does pain work? Dr. Sanjay Gupta Explains | Fresh Air"

• Certain types of pain. Many of those life-changing insights have not yet been made easily available to the public. His new book is an attempt to change that.

  about It Doesn't Have to Hurt · at 0:23

• Anti-inflammatories, and that would include medications like Advil and Motrin. inflammation is an essential part of healing after an injury. It protects the injury. It's like…

  about Motrin · at 20:25

• Yeah, the medication is called Susetrogene.

  about Susetrogene · at 27:14

• He had a condition known as CRPS, chronic regional pain syndrome. And he's wear he's he's in the hospital and he's got the stimulator in and he's, in the middle of a patient visit.

  about CRPS · at 37:09

Who and what is mentioned in this episode?

Books & papers

• It Doesn't Have to Hurt — Book · 1 mention · first at 0:33

Companies & orgs

• CNN — Company · 1 mention
  About anything else. My guest, neurosurgeon and CNN chief medical correspondent, Sanjay Gupta, writes that over the past few decades, we've learned more than ever about the…
• Emory University Hospital — Company · 1 mention · first at 0:40
  Gupta is also the host of the podcast Chasing Life. He's an associate professor of neurosurgery at the Emory University Hospital and is the author of four previous bestsellers. He's won several Emmy awards as well as two.

Products & tech

• Susetrogene — Product · Mentioned medication · 1 mention · first at 27:15
  Susetrogene is a medication that may be relevant in discussions about pain management.
• Motrin — Product · Mentioned medication · 2 mentions · first at 20:29
  Motrin is another common NSAID used for pain management.

Concepts & topics

• CRPS — Concept · 1 mention

Places & events

• CNN's Peabody Award — Event · 1 mention · first at 0:58
  Of marijuana, a subject we'll talk about a little later in the interview. He also contributed to CNN's Peabody Award-winning coverage of the devastation of Hurricane Katrina 20 years ago. Dr. Gupta, welcome back to Fresh Air.

Full transcript with timestamps

0:00 This is Fresh Air. I'm Terry Gross. When you're in pain, it can be hard to think about anything else. My guest, neurosurgeon and CNN chief medical correspondent, Sanjay Gupta, writes that over the past few decades, we've learned more than ever about the true nature of pain. We better understand what causes it, what may best relieve it, and what we can do to minimize or even eliminate certain types of pain. Many of those life-changing insights have not yet been made easily available to the public. His new book is an attempt to change that.

0:33 It's called It Doesn't Have to Hurt. Dr. Gupta is also the host of the podcast Chasing Life. He's an associate professor of neurosurgery at the Emory University Hospital and is the author of four previous bestsellers. He's won several Emmy awards as well as two DuPont Colombia awards, the most recent one for his reporting on the medical use of marijuana, a subject we'll talk about a little later in the interview. He also contributed to CNN's Peabody Award-winning coverage of the devastation of Hurricane Katrina 20 years ago. Dr. Gupta, welcome back to Fresh Air.

1:08 Thank you. Uh what what a pleasure. I always enjoy our conversations. Thank you for having me. So, I'll start with something I've never said to a guest before, which is tell us how you were impaled. This was just after your 12th birthday.

1:22 I was a kid. I was just after 12 years old, just turned 12. And I was um running through the neighborhood on a on a really beautiful day. I still remember. And there was a fence and I think it was sort of a a a row iron fence and it had some spikes on top. And I had, you know, obviously knew this fence. Um, typically I didn't try and jump over it. I went around it, but this day I just, I think I felt kind of invincible. And I decided to sort of try and vault myself over, you know, put one hand on and then vault your legs over. And uh, when I tried that, I didn't quite make it. and one of the spikes um caught me on my side and went in the back area uh of my side and out the front. So I was I was sort of stuck there on this on this fence. It was just high enough that I could not put my feet down to sort of, you know, hoist myself off the fence.

2:23 So it it pierced through your whole side. Yeah, it was the skin thankfully um as opposed to going into the chest or into the abdomen which would have been much worse. But it was sort of a classic inout sort of injury. And the story is interesting because the first of all I was there for a couple of minutes before anyone saw me which was really um a very strange feeling. I you know I knew somebody was going to find me but I think for a moment as a 12-year-old I thought what if they don't? And but eventually a neighbor came out and around the same time my mom sort of I don't know how she became aware but she kind of heard and and she came over and the neighbor went to go get this this big sort of wire cutter thing and he was going to basically cut it. Um but I I couldn't wait actually. So with my mom's help she put her foot down. I mean, she put her hands down so I could put my foot on her hands and I hoisted myself

3:23 off the spike. So, I actually came off the spike on my own before he cut it off.

3:30 Okay. So, now that we've established that you've experienced pain, what do you mean when you say that pain is created by the brain? In your case, pain was created by a very unnatural injury. Um but explain that the pain is created by the brain.

3:50 When whenever we have some sort of thing that happens in the periphery of our body, in this case it was my my back. Um signals are then sent to the brain to basically be processed to be translated and to be interpreted in some way. Um, when those signals go up, it's it's kind of like the brain is, you know, rapidly scrolling a social media feed and may say, "Okay, this is not that important. This is not that important. This is not that important. Oh, wait a second. This this is incendiary. This this particular post, let's pay a lot of attention to that." And then all of a sudden, that is sort of um uh the brain paying a lot of attention to a particular signal. In this case, a spike going through my my back. and and it determines at that point is this real number one or is it not is it noteworthy meaning how you know how significant is it and what should I do about it um there are certain things that happen before you

4:54 get to the brain uh which is that you might have like if you touch a hot pan your hand may jolt away from it that's happening reflexively there are certain nerve fibers that do that but when it comes to actually determining if something hurts and how much that is the brain. The brain determines whether or not you have pain.

5:13 The brain sometimes makes mistakes in its interpretation of pain too. And sometimes it sounds the alarm too loud and too long.

5:22 How does the brain make mistakes and what kind of pain does that lead to? That there are all sorts of mistakes that the brain can make. I mean, the brain is taking in so much information so quickly. Um, one of the best examples of how the brain can make a mistake is phantom limb pain. And in that case, a limb doesn't even exist anymore. It was amputated. It still hurts. It was amputated

5:49 and yet it still hurts. I think that's one of those those um sort of insights about the brain that I think led to a lot of learning about what exactly the brain's role was with pain. If the brain's deciding is is the decider of pain, can it create pain as well? And the answer is yes. Referred pain is another sort of mistake. So some people may be having um a what should be chest pain from a heart attack, but instead of having chest pain, they may have jaw pain. They may have just left arm pain. Some of that is referred from one place to another, and that's the way the brain is sort of interpreting it. And some of those are common referrals. We we know left arm pain for example is very associated with potential heart problem.

6:35 Uh doctors are sort of trained same thing with jaw pain. Um and then and then there's sorts of things where whatever the reason may be the brain continues to play the loop of pain over and over again. Um, I guess that's not so much a mistake as it is some maybe some sort of glitch where the pain loop doesn't stop and it's it's it just gets recycled over and over again and that and that's chronic pain. So those are some of the the ways that the brain can sort of either mistake or misinterpret the signals and and and the pain.

7:12 So, you know, a lot of times someone will go to see a doctor um and that they have chronic pain, but there's no evidence of what's causing it and the injury has healed. So, that's a kind of brain misinterpretation. What do you do about it? Some would argue that there is a reason and it may have to do with everything from adverse childhood events to even more recent trauma to to a a history of depression or anxiety. As someone said to me, I think it was um Mark Jensen at Mayo Clinic that chronic pain never occurs in isolation. It always occurs with baggage attached. And that baggage could be depression. Could be anxiety.

8:00 Could be adverse childhood experiences. Could be poor sleep. It could be things that maybe maybe seem more trivial. Could be you're having a really bad day. And something that wouldn't have hurt so much hurt a lot more because you're having a bad day. Maybe you had a bad call with your parent. whatever it may be. All these things, some more clear, some more arbitrary, seem to have some influence not just on your pain, but how much something's going to hurt and how long it will hurt.

8:28 So, one of the main themes of your book is if the brain interprets pain, can we get the brain to interpret it differently or at least turn down the volume of the alarm that it is sending? Do you believe the brain is really capable of being rewired like that? Yeah, I really do. And and I've seen it firsthand. The idea that meditation could provide uh relief. Um maybe not super durable. It's not something that lasts forever, but the idea that you could take someone's pain score from really terrible pain to a zero out of 10, and I'm not exaggerating, but a zero out of 10 for the 30 minutes that they are meditating, I think is is real proof of concept that there's a lot that can happen within the brain that can be trained without drugs, without without surgery. So, yeah, I think I think the brain can be trained that way. Do you have a scientific medical explanation for why why meditation can decrease pain

9:26 for at least an interval of time? We're not sure. To be fair and and most candid, Dr. Eric Garland is probably the the the nation's leading expert on this. He's out of the University of California, San Diego, and I spent a lot of time with him and asked that same question. And I think we don't know is the most honest answer. I think where people sort of circle around is this idea that um distraction could be one component of it could you know with pain people are usually hyperfocused on a particular sensation being able to take them out of that hyperfocus can be really helpful um for there there's other people who believe that you're actually decreasing the activity in certain areas of the brain uh specifically an area known as the anterior singulate cortex which is an area where pain is processed processed pain is processed in many areas of the brain but that's one of the primary areas but we we we don't know for sure

10:24 it would require I think a lot more testing to really you know look at people's brains while they meditate and understand what's happening and even then the answers may not be clear but what I think is clear based on lots of data is that people can get significant relief from meditation and I even asked Dr. Garland to to like give me context for what that means significant relief. I mean we can put numbers on it but what he he showed and what the p his most recent paper uh described was basically similar to five milligrams of oxycodone.

10:58 That's what meditation can do for you. Five milligrams of oxycodone is very effective. It also doesn't last forever. It it has a half-life. Meditation sort of the same way. It doesn't last forever, but you can reduce your pain scores to to near zero for for a period of time.

11:14 You actually meditated with the Daly Lama. I assume you were reporting on him, which is how you got to get the invitation to meditate with him. And you were very self-conscious and distracted because you were not only meditating and you know, you were doing it with the Daly Lama.

11:31 You reluctantly admitted that to him after the session was over. and tell us what he said to you.

11:39 He told me he also had a difficult time meditating which which really surprised me. I mean, you know, he's the Daly Lama. He's been meditating, you know, basically his whole life. Um, but he and he and he's a master meditator. He gets up, I think, I can't remember exactly what time, very early in the morning, 3:30 3:30 in the morning, and he meditates for a couple of hours before he starts his regular day. And that was the time that I was meditating with him. Um, but he he sort of conceded that it it can be challenging for people to to meditate. Um, you have to be you have to be very intentional about it. And um, but I learned a lot from him and I learned a lot from Herbert Benson and Eric Garland and all these people over my life about meditating and I think now I can get into it very very quickly. One of the points you make in the book is that researchers have found that pleasure and savoring, savoring food,

12:39 savoring pleasure, making sure you you make some space for pleasure or savoring in your life that it isn't a waste of time that you're actually rewiring your brain and countering pain in ways that strengthen with practice. Um, can you talk about that a little bit about what that might mean?

12:59 Sure. I think our default position probably as humans is to to um be be creatures that have gratitude and savor and and want to experience pleasure. That's no surprise. But what I think is is really interesting is that we we have this system within our body, the endogenous opioid system. Um, which is by endorphins, which means endo, which means inside the body, and fins, which is morphine. This is like our internal morphine system. Endorphine system. Um, we can activate this system in all sorts of different ways. And by activating, I mean exactly what it sounds like. You just basically re release a lot of these these endorphins, these basically personalized morphine molecules all throughout your body. And one of the the ways that they have shown can really facilitate that is to to not just practice gratitude, but to actively practice gratitude. Meaning actually savor something. I'm not just

14:07 grate grateful for this ice cream cone. I'm like just so enjoying this ice cream cone. I'm not just grateful for being able to look at this sunset. I am gazing at every different color in the sky and just taking it all in. It's a very active form of gratitude. Um and and it seems to be very associated with basically activating the indogenous opioid system, which is really fascinating to me. Some people would refer to this as sort of the mechanism behind placebo effect. Um, others say the placebo effect is going to be a lot more intricate than that. But when it comes to pain specifically, I think we know all these different things that we're talking about, whether it be meditation, whether it be savoring, all these things mechanistically probably have some component of activating this this really wonderful intricate system in our bodies. I guess it also teaches the person who is savoring or having

15:07 pleasure to distract themsself from pain because just as pain distracts you from the things you need to do, having pleasure really distracts you from the pain.

15:17 Yeah. I think it's becoming increasingly clear that these types of, you know, feel-good transmitters, endorphins are released in response to certain things that happen in our lives. You know, even going back to when I impaled myself on that fence, I think what was so interesting to me, and I was only 12 years old at the time, but when I reflected on it, it obviously hurt when I got impaled, but then I was basically pinned there on the fence for several minutes. And you know what, Terry? After a while, not only did it not hurt as much, I actually started to feel strangely a bit of euphoria.

15:59 really which is yeah which is really weird. But I think what happens for some people and probably I I fit into this is that when you do have an injury or or you know whatever might happen to you if you activate your endogenous opioid system for some people it reacts really vigorously like really really churns out a bunch of endorphins. And so you could have this really sort of ironic situation where you got a terrible injury and you're almost laughing. you're you're like, "Oh my god," you know, and it's I think it's a very protective sort of response from the body. Um, and not everyone responds the same way. Some people probably make fewer endorphins and maybe if it had been raining on me and I had hadn't eaten well that day, maybe I would have made fewer endorphins. But for a period of time, I really had no pain. In fact, I remember I reached behind with my hand at one point to feel the spike and and

16:52 and convinced myself that it was still there because for a little bit I I I wasn't even sure that this was real. I I wasn't feeling the pain that I thought I would have with this.

17:03 Are there any medications that exist or that are in development that could turn on the body's natural opioid system and release more endorphins? What we've done is basically try to give endorphins, right? We've we've instead of saying exactly what you said, which is can you harness the body's own EOS, endogenous opioid system, instead we said, oh, the body makes indogenous morphine, let us synthesize this molecule on our own. Let us create a drug that essentially attaches to the same receptors that these endorphins do, the mu receptors in the body. And that's that was sort of the genesis of opioids.

17:43 You know, so many techniques and medications that we use in real life take their inspiration from our human body, and that's one of them. So, we give opioids probably more so than focusing on teaching the body to release its own opioid system. And it's very different. While they both may have opioid in the name, they're very different. One thing is that with your own opioid system, it is very, very sensitive. So it can turn on and it can turn off really really well. So instead of having the lingering sort of side effects of of opioids and sed sedation and all these other things, the opioids that you make yourself can just be washed away very very quickly. Okay? So you have a quick on quick off sort of mechanism. The second thing is that impact on mood. Um it can actually make you euphoric. It can really improve your mood. And the third thing is that people with opioids often it it does not

18:41 suppress their memory. In fact, it may actually worsen it. Meaning and worsen it in this case means over remembering. So people who take opioids long term might actually start to have more pain because they become increasingly challenged to forget their pain.

18:58 Right. So in answer to uh researchers trying to develop an external form of endorphins, your answer is yeah, morphine and it didn't work out very well. But that's why pleasure is kind of like a prescription right now.

19:13 Yeah, I think pleasure savoring we know these things will release more opioids. People tend to feel better. So their pain tolerance goes up and and um their their remembering of unpleasant things goes down,

19:28 right? So all these things sort of happen. I always say if the indogenous opioid system didn't exist, women would probably never have more than one child.

19:37 You know, it can be a painful experience, but those opioids help with the pain, they help with the mood, and then that memory component is so fascinating to me. It can actually inhibit your memory. Like I talked to my wife about this, Rebecca, we have three girls and she's like, "Yeah, you know, I had the baby. I, you know, by the time we're having the second one, it wasn't like something she reflected on or was traumatized by." That's like one of the most significant things that happens in your life. Why? How could you possibly forget that? And maybe it's forgetting is not the right word, but how could you not remember it really vividly? And I think that's not by accident. I think that's really our our our own endorphins sort of doing their job in terms of pain, mood, and memory.

20:22 Let's talk about the latest understanding of inflammation and anti-inflammatories, and that would include medications like Advil and Motrin. Um, inflammation is an essential part of healing after an injury. It protects the injury. It's like putting a protective covering over the injury. But after a while, it seems like part of the problem is the inflammation itself. Sometimes it just won't go away or it just lingers too long or gets too large.

20:57 I think for the most part, inflammation has sort of gotten a bad rap. Um, I think that the idea that I don't want to have inflammation, I'll do everything I can to to get rid of inflammation if I have some sort of injury. That has been, I think, the the prevailing wisdom for a long time. And I think it's understandable. I I I think when you look at a a sprained ankle, for example, and it looks swollen and and red, the idea that I want to get rid of that that's associated with my pain makes intuitive sense, I think.

21:31 I think the idea that that inflammation serves a real purpose that not only is it sort of helping protect the the sight of injury but also sending all these various molecules to the site of injury to help with the healing I think is is also what's happening at that point. So when there was a study that came out that basically was trying to figure out who is most likely to have chronic pain after injuries. So if you look at the sprained ankle example, who is most likely to still have pain three months later? And interestingly, and the researchers weren't looking for this, what they found was that people who had the lowest levels of inflammation at the time of injury were the most likely to have chronic pain. So low levels of inflammation were were linked to chronic pain, not high levels of inflammation.

22:23 And I think for a long time people thought, "Oh, this guy's, you know, makes a lot of inflammation and he's probably going to be more likely to have pain." And almost the opposite turned out to be true. And and it was really relevant, I think, for people, especially in the sports world and and and um orthopedic surgeons and and physical therapists to sort of look at the the guidance that had typically been given to people, which was do everything you can to decrease inflammation. So some researchers are recommending now not taking anti-inflammatories right after an injury. When do researchers suggest that you do take anti-inflammatories?

22:59 I think it's if you can't tolerate it. That's the thing about pain is that everyone's threshold is going to be a little bit different. And I'm telling you that again if you haven't broken it, I'm telling you it's better to mobilize and not try and decrease inflammation. Maybe that alone will increase your pain threshold. I think for a lot of people, they think they need to take anti-inflammatories. Oh, this is bad. I got to I got to I got to treat that. That inflammation is not good. That's hurting my body. But if I flip the script on you and I say it's not bad for your body. That is exactly how your body is supposed to work. This is your body doing its job.

23:37 This may be a good time to mention that acetaminophen um for example Tylenol is not an anti-inflammatory.

23:43 That's right. in in your book and describing what kinds of uh problems could be treated with acetaminophen like Tylenol or ibuprofen like Advil and Motrin. You have under both categories under both types of uh uh um pills that they're really not for nerve pain. Why not? nerve pain or neuropathic pain um tends to be a different sort of pain. Um again with anti-inflammatories I guess it's inherent in the name the way that it works. Tylenol can help decrease inflammation but in a totally different mechanism. It's very good at reducing fever. Nerve pain really seems to be something that uh has to do with an abnormality of the way the nerves actually conducting signals. So, for example, when someone herniates a disc in their back or their neck and it puts pressure on the nerve, the nerve is is is not conducting the same way. It may be over sending some signals or undercending other signals. And what

24:49 you're really trying to do in that sort of situation is take certain meds that might balance out that nerve conduction again. And that's a different class of medications. There are several classes that can do this, but not typically uh anti-inflammatories. You know what I sometimes wonder? Can a numbing agent like lidocaine train the brain to think like, "Oh, there's no longer pain, so I can turn the pain signals like the unnecessary pain signals from chronic pain. I can turn them off now."

25:18 Can you trick a brain with a numbing agent? This is a It's a really interesting question. So, lidocaine and lidocaine is a good example of this. So, lidocaine is um it's a it's a what's called a sodium channel blocker. it uh it works you know whenever there's signals being transmitted in the body the way those signals move is through changes in ions sodium potassium ions like that if you can block certain certain of those sodium channels you can inhibit certain sensations in this case um pain or or sensation overall because lidocaine makes you numb it's not just taking away pain I don't know that there's any indication that they will necess necessarily train your brain in some way to to to have any benefit beyond the time that the lidocaine is there in terms of chronic pain. You can get rid of it for a period of time and we we use lidocaine uh to basically convince ourselves as surgeons that something

26:18 that we're about to do is going to be beneficial. So someone who has trigeminal neuralgia, I don't know if you've ever heard of that, but basically it's face pain and it's awful. Um it's lancinating face pain. tick delaroo it's called and it's it's one of the worst pains I think a human can actually feel um just these lightning bolts of pain in your face but anyways one of the things that we'll do is is we may inject the the the root of the nerve with some numbing agent like lidocaine and basically see if that takes away the pain and if it does that gives us an indication that it may be okay to heat up that area of the nerve or to use chemicals to sort of make that nerve not conduct anymore. Um, but that that's what these those types of numbing agents are are good for.

27:06 While you were writing your new book, a nonopioid pain medication was approved by the FDA. Tell us about it.

27:14 Yeah, the medication is called Susetrogene. It is a new pain medication and interestingly enough it is the first new pain medication that was approved by the FDA in the United States since 1998. Okay, more than a quarter century which I found really remarkable. I mean the last one was Celre and just to give some context the FDA will typically approve 40 to 50 new drugs a year but for pain which is a condition chronic pain that affects 20% of the population and according to some of the statistics we saw is the fastest growing condition now in the United States faster than cancer diabetes and dementia. It's pretty remarkable that we hadn't had a new option for pain but susetetrogroene is that new option and it is a fascinating story of how it came about. There were these families of circus performers in Karachi, Pakistan that got the attention of researchers whatever 25, 30 years ago.

28:21 And they saw that these these circus performers were able to do all these remarkable things like they could put sharp things through their appendages and they could walk on hot coals and do all that sort of stuff. But what they found was that when they were doing this, they could feel the coals on their feet and they could feel that they were hot. They just didn't have pain. And that's very different than what we were just talking about with lidocaine, which basically numbs you. So when you're numb, you you just have no sensation.

28:55 Here, they had sensation, they just didn't have pain. And that was pretty striking because it gave these researchers a clue as to which sodium channel blocker may be important when it came to just targeting pain and not sensation overall. They studied this family. They found that they had a gene in common. I think it's called SCN9. And basically for 25 years, these researchers tried to replicate what that gene was doing in the body, which was to take away pain. This family did not have pain. Now, one of the big challenges of creating a medicine like that is something you alluded to earlier, which is that you you didn't want to take away pain forever. Pain has utility. It it it can keep you safe. It can teach you lessons. Um, so they wanted to create a half-life for the drug. So, they basically now have an oral formulation.

29:49 I think it's I think it's twice a day formulation um to to basically try and treat pain. something that, you know, they hadn't had a new therapy for in over 25 years.

30:01 Let's talk about cannabis as a pain medication. You've done extensive reporting on cannabis as medicine. Um, what are some of your takeaways about the use of it for pain?

30:12 We spent a lot of time looking at the literature around cannabis. Um, and I walked into it thinking that if I really examined all this literature, there was going to be a pretty compelling case made for using cannabis for all sorts of different pains, but mostly neuropathic pain. This type of pain where the nerve is just not conducting well and either over or underconducting that's causing pain. Um, and and I walked away not as impressed to be quite honest as I thought I would be. And this is just the data talking. I will say it's hard to collect this data um when you're dealing with a substance that has been a level one substance in the United States for a long time. It's just really hard to get good studies.

30:56 It's hard to get funding probably too, right? Yeah. And then there's there's a lot of stigma attached to it. So people don't volunteer for the trials, whatever it might be. But having said that, the best available data seem to suggest that for about a third of the people, it could be pretty effective and maybe in some cases as effective as as the best other options for that neuropathic pain, gabapentin, neurontin medications like that. Terry, for about twothirds of people, it really did not seem to be that effective. And this is the case, I think, for about a third of people, they get significant benefit. And we don't quite know who those third of people are. We don't know what makes them different than the other two/3s that they're getting that kind of relief.

31:40 Is there any evidence that it might be the placebo effect? Yeah, I think that they're looking at all all sorts of different things including placebo effect. I think one of the researchers that I talked to, I think it was Julie Holland, she she kept making this point that I thought was a really good point that expectations and experience are inextricably linked. Um, especially when it comes to pain and the idea that if you really expect something to work, it's more likely to work. And that isn't necessarily your body or your brain playing tricks on you. That is probably again harnessing that endogenous opioid system.

32:21 You you you think it's going to work. Your body's like, "Oh yeah, I'm about to get relief. Wow. I'm I'm I'm already feeling it." You know, and and that in part could be those those endorphins starting to really ramp up.

32:34 Another way of kind of retraining the brain is deep brain stimulation, which uses electric impulses in parts of the brain, in relevant parts of the brain. It's used now for Parkinson's disease. There's like a little device that's implanted in the appropriate part of the brain and there's a remote control. You can turn it up or turn it down. Um, so how is that being used in pain relief or is it just in the real beginning stages? No, deep brain stimulation's been around for a long time and you know Parkinson's was one of the things but they also treat things like obsessivecompulsive disorder now even with Tourette's

33:14 things like that with deep brain stimulation. It's pretty fascinating. The idea of using it for pain sort of came about in a very interesting way. I think one of the big questions neuroscientists have been percolating on for a long time is we know pain is processed in the brain. Is there a way to figure out where and how it's processed in the brain and also to measure it in some way? Right now we're primarily relying on, you know, smiley or frowny faces for patients to tell us how much pain they have, but is there a way to objectify that in some way? And I think that's really how these researchers Prasad Travolkar and others at UCSF started approaching this was to to say okay these patients who have pain and these were the worst of the worst patients. They had pain that was so refractory they had sometimes dozens of operations spinal cord stimulators taking many generations of pain medications and they just weren't

34:12 getting relief. They were the ones who qualified for the trial. And the trial basically consisted of putting a bunch of stimulators all over the brain, left side and right side and basically just listening to the brain. Uh when the person had pain, they recorded it and they would do this for months and they would basically say, "Okay, whenever the patient has pain, what what what happened in the brain at that point? Was there a transfer of energy somewhere? Is there something to see?" And using you know machine learning now being able to analyze a lot of that data because it's a lot of data.

34:47 You have 84 billion neurons in the brain. They were able to find those areas in some ways measure them seeing how much energy was actually changing in that part of the brain which gave some sort of correlation with the significance of pain or the severity of pain. And they even got to the point where they could start to predict that change of energy before the patient felt it. So they would see a change in energy in the brain before someone actually started to consciously uh experience pain. And they even got to the point where they could then interrupt it much like you do with Parkinson's. You gave a little jolt of electricity at that point and you basically interrupt that that pain signaling at that point in the brain. It was proof of concept I think to your fundamental question which is this is not only is this the formative stages this isn't something that's ever going to be you know for the masses when no

35:43 one is suggesting that that brain surgery which is what these patients had uh is going to be the answer but I think what it has proven is that brain pain is very much in the brain and we can objectify it in ways that we did not fully appreciate before

35:59 that's fascinating Is AI being used as part of this to process the data? Yes. I think if you talk to these researchers, I don't think they could have done this probably without at least these large machine learning models. It is so much data. I mean, they had some idea where pain processing is likely to occur. There's some areas of the brain that are more likely to process pain than others, but there is no single pain processing center. So they they needed to look all over the brain and and then just spend this time correlating lots and lots of data with with all these energy transfers that are happening in the brain because your brain is constantly communicating. And I got to tell you, I got to spend time with the with the patient who got tremendous success with this strategy that I've described and he just had terrible pain for decades.

36:59 Um, I I you know, it's the kind of pain I'm not sure I could have tolerated in my own life. The way he described it, just like these snakes constantly biting his feet and razor blades all the time. He had a condition known as CRPS, chronic regional pain syndrome. And he's wear he's he's in the hospital and he's got the stimulator in and and he's, you know, in the middle of a patient visit and all of a sudden he goes, "Whoa." And they said, "What?" He goes, "I don't have pain. The veil of pain just went away. I I've had this veil over my face and over my, you know, brain for for decades, and it just got lifted. I don't have pain." It was it was the wildest thing. Um, I don't know where the research goes in terms of what this is going to mean for the masses, but it was really really uh amazing to see that kind of relief.

37:49 It sounds Gupta, thank you so much for talking with us. Thanks, Terry. I always look forward I write books just so I can have these conversations with you.

Questions about this episode

Who speaks in "How does pain work? Dr. Sanjay Gupta Explains | Fresh Air"?

Terry Gross (Host), Dr. Sanjay Gupta (Guest).

What is "How does pain work? Dr. Sanjay Gupta Explains | Fresh Air" about?

Dr. Sanjay Gupta discusses the complexities of pain, exploring its causes, potential relief methods, and the available insights that could change public understanding, as detailed in his book "It Doesn't Have to Hurt." He emphasizes the ongoing advancements in pain management and the importance of making this knowledge accessible to the wider community.

What is mentioned in this Fresh Air episode?

7 people, works and ideas are mentioned, including It Doesn't Have to Hurt, Susetrogene, CNN, Motrin, Emory University Hospital, CNN's Peabody Award. Each one on this page links to its own page with every episode that mentions it.

How long is "How does pain work? Dr. Sanjay Gupta Explains | Fresh Air"?

The episode runs 38 min; the transcript is about 6,587 words in 64 timestamped sections.

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