How Does Pain Work? Dr. Sanjay Gupta Explains

Summary

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Fresh Air: "How Does Pain Work? Dr. Sanjay Gupta Explains"

Date: September 4, 2025
Host: Terry Gross
Guest: Dr. Sanjay Gupta, neurosurgeon and CNN chief medical correspondent

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Overview

In this engaging episode of Fresh Air, host Terry Gross sits down with Dr. Sanjay Gupta to unpack the latest science behind pain—how we experience it, why our brains can sometimes get pain “wrong,” and what new techniques and treatments are emerging. Drawing on his new book, It Doesn’t Have to Hurt, Dr. Gupta shares both personal anecdotes and the newest medical findings, offering hope and insight for those who struggle with chronic and acute pain.

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Key Discussion Points & Insights

Dr. Gupta’s Personal Story: Childhood Impalement and Early Lessons on Pain

• At 12, Dr. Gupta was impaled on a wrought iron fence. Surprisingly, he felt less pain than expected, leading to his fascination with the science of pain ([01:44]).
• Not all body parts have the same density of pain receptors (nociceptors); the back, for example, is less sensitive than hands or feet ([04:10]).

Quote:

“When I reflected on it … after a while, not only did it not hurt as much, I actually started to feel, strangely, a bit of euphoria.”
— Dr. Sanjay Gupta ([15:57])

The Brain’s Central Role: Interpreting Pain

• Pain isn’t experienced at the site of injury alone; it’s constructed by the brain ([05:37]).
• The brain can misinterpret pain signals—leading to phenomena like phantom limb pain or “referred” pain, where, for example, a heart attack presents as jaw pain ([07:02]).

Quote:

"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.”
— Dr. Sanjay Gupta ([06:19])

Chronic Pain and “Pain Loops”

• Chronic pain often outlasts physical injury due to persistent brain “loops,” sometimes tied to trauma, depression, anxiety, or even minor daily stressors ([08:44]).
• Chronic pain never occurs in isolation and is compounded by emotional and psychological “baggage” ([08:44]).

Can We Rewire How the Brain Interprets Pain?

• Dr. Gupta asserts the brain can be “trained” to turn down the volume on pain.
• Mindfulness and meditation can reduce perceived pain to zero for short periods—comparable to the relief from 5mg of oxycodone ([09:55], [11:57]).
• He shares a personal experience meditating with the Dalai Lama, noting even lifelong meditators admit to difficulty focusing ([12:45]).

Quote:

“The idea that you could take someone’s pain score from really terrible pain to a 0 out of 10 … for the 30 minutes that they are meditating, I think is real proof of concept.”
— Dr. Sanjay Gupta ([09:55])

The Power of Pleasure, Savoring, and Endorphins

• Actively savoring pleasure (e.g., enjoying food, gratitude) can biologically activate the body’s endorphins—internal “morphine,” raising pain tolerance and enhancing mood ([13:47]).
• The placebo effect may, in part, come from harnessing this endogenous opioid system ([14:30]).

Quote:

“We can activate this system in all sorts of different ways … not just practice gratitude, but to actively practice gratitude.”
— Dr. Sanjay Gupta ([13:47])

Medications: Opioids vs. Endogenous Opioids, Anti-inflammatories, and New Options

• Prescribed opioids mimic endorphins, but are less precise and can lead to over-remembering pain; our own “in-house” opioids turn off more cleanly ([17:48]).
• New pain medication, suzetragine, targets sodium channels in the brain, inspired by a Pakistani family unable to feel pain—offers sensation without numbness ([30:16]).

Quote:

“The last [pain] drug was approved in 1998 ... for pain, which is a condition that affects 20% of the population ... it’s pretty remarkable we hadn’t had a new option.”
— Dr. Sanjay Gupta ([30:16])

Inflammation and NSAIDs

• Inflammation is vital for healing; suppressing it immediately with anti-inflammatory drugs may worsen outcomes and increase risk of chronic pain ([23:07]).
• NSAIDs (like Advil) are not helpful for nerve pain, which needs different approaches ([25:34], [25:58]).

Cannabis for Pain

• Research is mixed; for one-third of chronic pain patients, cannabis is as effective as standard treatments, but it fails for two-thirds ([33:02]).

Quote:

“For about a third of the people it could be pretty effective … for about 2/3 of people, it really did not seem to be that effective.”
— Dr. Sanjay Gupta ([33:43])

Deep Brain Stimulation and AI

• A cutting-edge treatment places stimulators in the brain to “interrupt” pain in highly refractory cases. Machine learning is key to mapping pain signatures in the brain ([35:45], [38:31]).
• Discussion of a patient with chronic regional pain syndrome whose lifelong pain vanished when stimulation was activated ([38:38]).

Quote:

"The veil of pain just went away ... I've had this veil over my face and over my brain for decades and it just got lifted."
— Dr. Sanjay Gupta (relating a patient story, [39:36])

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Notable Quotes & Memorable Moments

• On meditation’s power:
  “What [meditation] showed was basically similar to 5 milligrams of oxycodone. That’s what meditation can do for you.”
  — Dr. Sanjay Gupta ([11:57])

• On placebo and expectation:
  “Expectations and experience are inextricably linked, especially when it comes to pain.”
  — Dr. Sanjay Gupta, quoting researcher Julie Holland ([34:27])

• On the future:
  “Pain is very much in the brain, and we can objectify it in ways that we did not fully appreciate before.”
  — Dr. Sanjay Gupta ([38:58])

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Timestamps for Key Segments

• Personal story of being impaled: [01:44]–[05:16]
• Pain as brain construct & misinterpretation: [05:37]–[07:13]
• Chronic pain and psychology: [08:44]
• Brain training/meditation: [09:55]–[12:45]
• Endorphins/savoring/pleasure: [13:47]–[15:57]
• Opioid system comparison and memory: [17:48]–[19:39]
• Inflammation and treatment myths: [23:07]–[25:27]
• New pain medication (suzetragine): [30:16]
• Cannabis and pain: [33:02]–[34:27]
• Deep brain stimulation and AI: [35:45]–[39:36]

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Tone and Style

Richly anecdotal, evidence-based, and approachable—Dr. Gupta and Terry Gross maintain a conversational, relatable, and often empathetic tone, demystifying the science while offering hope and practical advice for pain sufferers.

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This summary covers all major topics, using speaker-attributed quotes and clear time stamps, and should provide a comprehensive, engaging overview for new listeners or those looking for the episode’s key insights.

Transcript

[Dr. Sanjay Gupta]

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[Terry Gross]

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 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. 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 Columbia 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.

[Dr. Sanjay Gupta]

Thank you. What a pleasure. I always enjoy our conversations. Thank you for having me.

[Terry Gross]

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.

[Dr. Sanjay Gupta]

I was a kid. I was just after 12 years old, just turned 12. And I was running through the neighborhood on a really beautiful day. I still remember. And there was a fence and I think it was sort of a wrought iron fence and it had some spikes on top. And I had, you know, obviously knew this fence. Typically I 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 when I tried that, I didn't quite make it. And one of the spikes caught me on my side and Went in the back area of my side and out the front. So I was sort of stuck there 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.

[Terry Gross]

So it pierced through your whole side?

[Dr. Sanjay Gupta]

Yeah, it was the skin, thankfully, as opposed to going into the chest or into the abdomen, which would have been much worse. But it was sort of a classic in out sort of injury. And the story is interesting because first of all, I was there for a couple of minutes before anyone saw me, which was really a very strange feeling. I knew somebody was gonna find me. But I think for a moment as a 12 year old, I thought, what if they don't? 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 she came over and the neighbor went to go get this big sort of wire cutter thing and he was going to basically cut it. But 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 off the spike. So I actually came off the spike on my own before he cut it off.

[Terry Gross]

Ouch. And you read that the tissues in the torso don't have as many nerves and as much sensitivity as other parts of the body.

[Dr. Sanjay Gupta]

Yeah, this was, I think, the first time I started sort of thinking about pain in a different way, because first of all, and I can tell you what it felt like, which was very different than what I would have imagined it to feel like before it happened. But yeah, one of the things is that the skin on the back, it has fewer of these nociceptors, these receptors that will actually transmit pain. And by fewer, it also means that they're less dense over an area. When you have a higher density of nociceptors, that's when they're going to be more sensitive and they're transmitting signals very quickly because they're so close together, jam packed together. When those nociceptors are further apart, you have less sensation. You have less. What is called two point discrimination. So your ability to tell the distance between two points is much greater on the back. The two points have to be much, much further apart before you can really tell that there's two points. And it didn't hurt as much as I think many other parts of the body would have.

[Terry Gross]

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. But explain that the pain is created by the brain.

[Dr. Sanjay Gupta]

Whenever we have some sort of thing that happens in the periphery of our body. In this case, it was my back. Signals are then sent to the brain to basically be processed, to be translated and to be interpreted in some way. When those signals go up, it's kind of like the brain is 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, important. Oh, wait a second. This. This is incendiary. This particular post, let's pay a lot of attention to that. And it determines at that point, is this real, number one, or is it not? Is it noteworthy? Meaning how significant is it and what should I do about it? There are certain things that happen before you get to the brain, which is that you might have, like if you touch a hot pan, your hand maybe 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.

[Terry Gross]

The brain sometimes makes mistakes in its interpretation of pain, too. And sometimes it sounds the alarm too loud and too long. How does the brain make mistakes, and what kind of pain does that lead to?

[Dr. Sanjay Gupta]

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.

[Terry Gross]

It was amputated.

[Dr. Sanjay Gupta]

It was amputated, and yet it still hurts. I think that's one of those 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 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 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. And some of those are common referrals. We know left arm pain, for example, is very associated with potential heart problem. Doctors are sort of trained. Same thing with jaw pain. 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. I guess that's not so much a mistake as it is maybe some sort of glitch where the pain loop doesn't stop and it just gets recycled over and over again. And that's chronic pain. So those are some of the ways that the brain can sort of either mistake or misinterpret the signals and the pain.

[Terry Gross]

So a lot of times someone will go to see a doctor and 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.

[Dr. Sanjay Gupta]

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 a history of depression or anxiety. As someone said to me, I think it was 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, could be adverse childhood experiences, could be poor sleep, it could be things that 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.

[Terry Gross]

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?

[Dr. Sanjay Gupta]

Yeah, I really do. And I've seen it firsthand. The idea that meditation could provide relief, 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 0 out of 10, and I'm not exaggerating, but a 0 out of 10 for the 30 minutes that they are meditating, I think is real proof of concept that there's a lot that can happen within the brain that can be trained without drugs, without surgery. So, yeah, I think the brain can be trained that way.

[Terry Gross]

Do you have a scientific, medical explanation for why meditation can decrease pain for at least an interval of time?

[Dr. Sanjay Gupta]

Dr. Eric Garland is probably 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 distraction could be one component of it. You know, with pain People are usually hyper focused on a particular sensation. Being able to take them out of that hyper focus can be really helpful. There's other people who believe that you're actually decreasing the activity in certain areas of the brain. Specifically an area known as the anterior cingulate cortex, which is an area where pain is processed. Pain is processed in many areas of the brain, but that's one of the primary areas. But we don't know for sure. It would require, I think, a lot more testing to really 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 give me context for what that means. Significant relief. I mean, we can put numbers on it. But what he showed and what his most recent paper described was basically similar to 5 milligrams of oxycodone. That's what meditation can do for you. Five milligrams of oxycodone is very effective. It also doesn't last forever. It has a half life. But meditation sort of the same way, it doesn't last forever, but you can reduce your pain scores to near zero for a period of time.

[Terry Gross]

You actually meditated with the Dalai 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 Dalai Lama. You reluctantly admitted that to him after the session was over. And tell us what he said to you.

[Dr. Sanjay Gupta]

He told me he also had a difficult time meditating, which really surprised me. I mean, you know, he's the Dalai Lama. He's been meditating basically his whole life. And he's a master meditator. He gets up, I think 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. But he sort of conceded that it can be challenging for people to meditate. You have to be very intentional about it.

[Terry Gross]

One of the points you make in the book is that researchers have found that pleasure and savoring, savoring food, savoring pleasure, making sure 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, can you talk about that a little bit about what that might mean.

[Dr. Sanjay Gupta]

Sure. I think our default position probably as humans is to be creatures that have gratitude and savor and want to experience pleasure. That's no surprise. But what I think is really interesting is, is that we have this system within our body, the endogenous opioid system, which is endorphins, which means endo, which means inside the body, and fins, which is morphine. This is like our internal morphine system, endorphin system. We can activate this system in all sorts of different ways. And by activating, I mean, exactly what it sounds like, you just basically release a lot of these. These endorphins, these basically personalized morphine molecules all throughout your body. And one of the ways that they have shown can really facilitate that is to not just practice gratitude, but to actively practice gratitude, meaning actually savor something. I'm not just grateful for this ice cream cone. I'm like, just so enjoying this ice creamy 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. And it seems to be very associated with basically activating the endogenous opioid system, which is really fascinating to me. Some people would refer to this as sort of the mechanism behind placebo effect. Others say the placebo effect is gonna 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 really wonderful, intricate system in our bodies.

[Terry Gross]

I guess it also teaches the person who is savoring or having pleasure to distract themselves from pain. Because just as pain distracts you from the things you need to do, having pleasure really distracts you from the pain.

[Dr. Sanjay Gupta]

Yeah. I think it's becoming increasingly clear that these types of feel good transmitters, endorphins, are released in response to certain things that happen in our lives. 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 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, really. Which is. Yeah. Which is really weird. But I think what happens for some people, and probably I fit into this, is that when you do have an injury or 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 get a terrible injury and you're almost laughing. You're like, oh, my God, you know? And I think it's a very protective sort of response from the body. And not everyone responds the same way. Some people probably make fewer endorphins. And maybe if it had been raining on me and I 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 convince myself that it was still there.

[Terry Gross]

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?

[Dr. Sanjay Gupta]

What we've done is basically try to give endorphins, right? 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 endogenous 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 was sort of the genesis of opioids. 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 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 opioids and sedation and all these other things, the opioids that you make yourself can just be washed away very, very quickly. The second thing is that impact on mood. It can actually make you euphoric. It can really improve your mood. And the third thing is that people with opioids, often, it does not suppress their memory. In fact, it may actually worsen it 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.

[Terry Gross]

Right. So in answer to our 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.

[Dr. Sanjay Gupta]

Yeah, I think pleasure savoring, we know these things will release more opioids. People tend to feel better, their pain tolerance goes up and their remembering of unpleasant things goes down. So all these things sort of happen. I always say if the endogenous opioid system didn't exist, women would probably never have more than one child. 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. 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. 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 own endorphins sort of doing their job in terms of pain, mood and memory.

[Terry Gross]

Okay, we need to take another break here, but there's plenty more to talk about. If you're just joining us, My guest is Dr. Sanjay Gupta, CNN's chief medical correspondent and author of the new book it doesn't have to Hurt. We'll talk more about pain and pain relief after a short break. I'm Terry Gross, and this is FRESH.

[Dr. Sanjay Gupta]

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[Terry Gross]

Let's talk about the latest understanding of inflammation and 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 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.

[Dr. Sanjay Gupta]

I think for the most part, inflammation has sort of gotten a bad rap. I think that the idea that I don't want to have inflammation, I'll do everything I can to get rid of inflammation if I have some sort of injury. That has been, I think, the prevailing wisdom for a long time, and I think it's understandable. I think when you look at a sprained ankle, for example, and it looks swollen and red, the idea that I want to get rid of that that's associated with my pain makes intuitive sense. I think the idea that that inflammation serves a real purpose, that not only is it sort of helping protect the site of injury, but also sending all these various molecules to the site of injury to help with the healing, I think is also what's happening at that point. So, so 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 linked to chronic pain, not high levels of inflammation. And it was really relevant, I think, for people, especially in the sports world and orthopedic surgeons and physical therapists to sort of look at the guidance that had typically been given to people, which was do everything you can to decrease inflammation.

[Terry Gross]

So some researchers are recommending now not taking anti inflammatories right after an injury. So when do researchers suggest that you do take anti inflammatories?

[Dr. Sanjay Gupta]

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 again if you haven't broken it. I'm telling you, it's better to mobilize and not try and decrease inflammation. I think for a lot of people, they think they need to take anti inflammatories. Oh, this is bad. I gotta treat that. That inflammation's 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.

[Terry Gross]

This may be a good time to mention that acetaminophen, for example, Tylenol, is not an anti inflammatory.

[Dr. Sanjay Gupta]

That's right.

[Terry Gross]

In your book. In describing what kinds of problems could be treated with acetaminophen like Tylenol or ibuprofen like Advil and Motrin, you have under both categories, under both types of pills that they're really not for nerve pain. Why not?

[Dr. Sanjay Gupta]

Nerve pain or neuropathic pain tends to be a different sort of pain. 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 has to do with an abnormality of the way the nerve's 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 not conducting the same way. It may be over sending some signals or under sending other signals. And what 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 anti inflammatories.

[Terry Gross]

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. Can you trick a brain With a numbing agent.

[Dr. Sanjay Gupta]

This is a really interesting question. And lidocaine is a good example of this. So lidocaine is what's called a sodium channel blocker. 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 pain 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 necessarily train your brain in some way 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 use lidocaine to basically convince ourselves as surgeons that something 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 it's lancinating face pain. Tic Delarux, it's called. And it's one of the worst pains I think a human can actually feel, just these lightning bolts of pain in your face. But anyways, one of the things that we'll do is we may inject 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. But that's what those types of numbing agents are good for.

[Terry Gross]

Well, it's time for another break, so let me reintroduce you. If you're just joining us, my guest is neurosurgeon Dr. Sanjay Gupta, CNN's chief medical correspondent. His new book is called it doesn't have to Hurt. We'll talk more after a break. This is FRESH air.

[Dr. Sanjay Gupta]

Hey, everybody, it's Ian and Mike, the hosts of how to Do Everything. That's the show where we take your questions and find overqualified experts to answer them. Alex asked us to write his out of office email message, but we don't know how to write. So we called up US Poet Laureate Ada Limon.

[Terry Gross]

Is this National Public Radio?

[Dr. Sanjay Gupta]

Sort of. Technically, yes. Season two just dropped. Listen to the how to Do Everything podcast from NPR on How to Do Everything. We take your questions and find phenomenal experts to answer them because we love you. Elizabeth asked us, how do I exercise while I'm in my car. And because we love Elizabeth, we rang up our our favorite bodybuilder turned actor turned governor turned actor. Hello, Arnold. Hello. We're here to talk to you today from npr. Very nice. Season two just dropped. Listen to how to Do Everything from npr. I'm Peter Sagal.

[David Biancooli]

NPR is very serious.

[Dr. Sanjay Gupta]

Mostly it treats newsmakers with all due respect almost all the time.

[David Biancooli]

It brings you the most important information.

[Dr. Sanjay Gupta]

About the issues that really matter usually. And it never asks famous people about things they don't know anything about except once in a while. Join us for the great exception. Listen to Wait, wait, Don't tell me the news quiz from npr.

[Terry Gross]

While you were writing your new book, a non opioid pain medication was approved by the fda. Tell us about it.

[Dr. Sanjay Gupta]

Yeah. The medication is called suzetragine. 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, which I found really remarkable. I mean, the last one was Celebrex. 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 zoozetrogene 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. And they saw that 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 numbing, you just have no sensation 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. Now, one of the big challenges of creating a medicine like that is something you alluded to earlier, which is that you didn't want to take away pain forever. Pain has utility. It can keep you safe, it can teach you lessons. So they wanted to create a half life for the drug. So they basically now have an oral formulation, I think it's twice a day formulation to basically try and treat pain, something that, you know, they hadn't had a new therapy for in over 25 years.

[Terry Gross]

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

[Dr. Sanjay Gupta]

We spent a lot of time looking at the literature around cannabis 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's just not conducting well and either over or under conducting, that's causing pain. 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 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.

[Terry Gross]

It's hard to get funding probably too. Right?

[Dr. Sanjay Gupta]

Yeah. And then 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 the best other options for that neuropathic pain. Terry, for about 2/3 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 2/3 that they're getting that kind of relief.

[Terry Gross]

Is there any evidence that it might be the placebo effect?

[Dr. Sanjay Gupta]

Yeah, I think that they're looking at 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 kept making this point that I thought was a really good point, that expectations and experience are inextricably linked, 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. You think it's going to work. Your body's like, oh, yeah, I'm about to get relief. Wow, I'm already feeling it. You know? And that, in part, could be those endorphins starting to really ramp up.

[Terry Gross]

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. So how is that being used in pain relief? Or is it just in the real beginning stages?

[Dr. Sanjay Gupta]

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 obsessive compulsive disorder. Now, even with Tourette's, 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 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 Srivalkar and others at UCSF started approaching this was 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 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. 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 happened in the brain at that point? Was there a transfer of energy somewhere? Is there something to See, and using machine learning now, being able to analyze a lot of that data, because it's a lot of data. 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. 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 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. No one is suggesting that brain surgery, which is what these patients had, is going to be the answer. But I think what it has proven is that pain is very much in the brain, and we can objectify it in ways that we did not fully appreciate before.

[Terry Gross]

That's fascinating. Is AI being used as part of this to process the data?

[Dr. Sanjay Gupta]

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 needed to look all over the brain and then just spend this time correlating lots and lots of data with all these energy transfers that are happening in the brain because your brain is constantly communicating. And I gotta tell you, I got to spend time with the patient who. Who got tremendous success with this strategy that I've described. And he just had terrible pain for decades. 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 in the hospital and he's got the stimulator in, and he's in the middle of a patient visit, and all of a sudden he goes, oh. And they said, what? He goes, I don't have pain. The veil of pain just went away. I've had this veil over my face and over my brain for decades and it just got lifted. I don't have pain. It was the wildest thing. 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 amazing to see that kind of relief.

[Terry Gross]

Well, on that note, Sanjay Gupta, thank you so much for talking with us.

[Dr. Sanjay Gupta]

Thanks, Terry. I always look forward. I write books just so I can have these conversations with you. Really appreciate your time.

[Terry Gross]

I appreciate yours. Thank you so much. And be well. Thank you. Sanjay Gupta is a neurosurgeon and CNN's chief medical correspondent. His new book about pain is called it doesn't have To Hurt. After we take a short break, TV critic David Biancooli will review the new HBO crime series Task by the creator of Mayor of Easttown. It stars Mark Ruffalo. This is FRESH air.

[Dr. Sanjay Gupta]

Military commanders, intelligence officials, diplomatic power players. They know things you may not about where the world is headed. And we will pull back the curtain. Their thinking on sources and methods. NPR's new National Security podcast. Our team will help you understand America's shifting role in the world. Listen to Sources and Methods from npr. If you're a robot, this might not be the show for you. But if you're a human with hopes, dreams and bills to pay, the Life Kit podcast might be just what you need. Three times a week, Life Kit brings.

[Terry Gross]

You a fresh set of solutions to.

[Dr. Sanjay Gupta]

Help you tackle topics big and small, from how to save money on groceries to how to bring the house down at karaoke. You know, human stuff. Listen to the Life Kit Podcast from npr. Presentado por mi Marielle Segarra. Shortwave thinks of science as an invisible force showing up in your everyday life, powering the food you eat, the medicine you use, the tech in your pocket.

[Terry Gross]

Science is approachable because it's already part of your life.

[Dr. Sanjay Gupta]

Come explore these connections on the Short.

[Terry Gross]

Wave podcast from NPR. The creator of HBO's hit show Mare of Easttown has returned with another HBO crime series set in the suburbs of Philadelphia and the Poconos. It's called Task and stars Mark Ruffalo as an FBI agent running a small task force. It premieres this Sunday, then streams on HBO Max. Our TV critic David Biancooli has this review.

[David Biancooli]

Mare of Easttown, which starred Kate Winslet as a small town Pennsylvania police detective, was a terrific crime drama. It was as much a character study as a detective story and made the most of both its characters and its locations. Its writer, creator Brad Inglesby, leaned into the miniseries or limited series format because it was a one time story. Even the most central characters might die at any point, upping the tension considerably with its settings, its accents, and its deeply drawn, deeply flawed people. Mayor of Easttown was a very memorable HBO drama. So memorable it hardly seems possible that it's been four years since it was televised. But now Inglesby is back with a new drama set in Pennsylvania. Once again, we get references to Wawa and Scrapple, visits to Rita's water ice and lots of Delaware county or Delco back roads and thick accents. This time it's a seven part drama called Task, which HBO will roll out weekly on Sundays. And this time, the actor at its center, instead of Kate Winslet, is Mark Ruffalo. On the big screen in the Marvel universe, Ruffalo plays Bruce Banner and the Hulk. But on tv, he's specialized in starring in limited series or miniseries that showcase him without any reliance on special effects. In Netflix's World War II drama All the Light We Cannot See, he played the father of a blind French girl. In HBO's I know this Much Is True, he played twin brothers, one of whom had mental health issues. He was excellent in both dramas. And now in Task, Mark Ruffalo serves up his best small screen role of all as FBI agent Tom Brandis. When we meet Tom, he has a bit of a drinking problem, just as Kate Winslet's character did in Mayor of Easttown, and like her, he has uneasy relationships with his friends and family. As the drama opens, Tom is preparing for a dull day staffing an FBI recruitment desk at a local career fair. Right away, as he introduces himself to a young man who stops to look at a pamphlet, Tom hints at some of the deeper currents lurking underneath his laid back demeanor.

[Dr. Sanjay Gupta]

Tom Brandis. Kyle. There you go. Now take one of these. Recent grad? Yeah. Widener. Congratulations. What's your degree in? Accounting. Which doesn't exactly make much sense for me to be stopping at an FBI booth. You'd be surprised. I majored in philosophy as an undergrad. I became a priest for eight years. And I'm here now talking to you about what the FBI has to offer. We have a very wide reach here at the Bureau. This is like an actual job in the FBI? Well, I'm a field agent normally. That's my just taking a little time off. I'll be back on assignment again soon, hunting down the bad guys. Watch out, bad guys.

[David Biancooli]

A lot of minor mysteries are revealed in that brief exchange. Why did Tom become a priest and why did he stop? Why did he take time off from Active duty on the force. And when will he return to chase those bad guys? That last question is answered almost immediately. Tom is summoned by his captain, who's played with her own brand of weariness and sarcasm by the wonderful Martha Plimpton. The captain has a job for him whether he likes it or not.

[Terry Gross]

SAC called me.

[Dr. Sanjay Gupta]

They want me to put together a task force. I know, I'm sorry. I assigned Maria Herrera to lead, but she got ordered to bed rest. What is it? Oh, it's something about a leaky uterus. What's the job? Sorry. There's been a spate of home invasions. Montco and Delco counties. Two, sometimes three man crew.

[Terry Gross]

Middle of the night.

[Dr. Sanjay Gupta]

They're targeting drug houses through DEA informants. We know of at least nine houses.

[Terry Gross]

That have been hit, and of those.

[Dr. Sanjay Gupta]

Nine, seven belong to members of a motorcycle gang, the Dark Hearts. You ever run across them? I brush with them in Violent Crimes. They just found two bodies last week behind a concrete plant in Ridley. They're low level distributors, but the Dark Hearts are retaliating, blaming other gangs. They're spinning. We need to find this crew before turf war escalates.

[David Biancooli]

From that simple seed, everything in Task sprouts and spreads. Tom gets paired with the three young members of his new task force, each of them with their own quirks, personalities and past problems. As for the people they're hunting, both the bikers and the home invaders, all of them have, well, delineated problems and personalities too. Tom Pelfrey as the masked robber named Robbie and Amelia Jones as his niece Maeve are two of the many standout actors and characters in this strong, rich cast. Inglesby delivers surprises and cliffhangers in every episode, but the most powerful elements to me are the many long, intimate conversations between the various characters about faith and death, love and duty, and family and responsibility. Ruffalo's FBI agent, it turns out, is a lot more complicated than he seems to. You can say the same for Ruffalo's nuanced performance and for all of this new HBO series called Task. Task has a lot of tension and action and conflict, but also has a lot of heart and emotion and deeper meaning. I've seen the entire seven part drama, and the ideas and the emotions in Task end up outweighing the mystery in the action. And they linger. I expect I'll be thinking about Task for quite a while.

[Terry Gross]

David Biancooli is a professor of television studies at Rowan University. He reviewed the new series Task. It premieres on HBO Sunday, then streams on HBO Max. If you'd like to find out what's happening behind the scenes of our show and get our producers recommendations for what to watch, read and listen to. Subscribe to our free [e-mail] Fresh Air Fresh Air's executive producer is Danny Miller. Our technical director and engineer is Audrey Bentham. Our managing producer is Sam Brugger. Our interviews and reviews are produced and edited by Phyllis Myers, Roberta Shurrock, Anne Marie Boldonado, Lauren Krenzel, Teresa Madden, Monique Nazareth, Susan Yakundi, Anna Bauman and John Sheehan. Our digital media producer is Molly CV Nesper. Our consulting visual producer is Hope Wilson. Thea Chaloner directed today's show. Our co host is Tanya Mosley. I'm Terry Gross.

[Dr. Sanjay Gupta]

This message comes from NPR sponsor Shopify. Start selling with Shopify today. Whether you're a garage entrepreneur or IPO ready, Shopify is the only tool you need to start, run and grow your business without the struggle.

[Terry Gross]

Go to shopify.com NPR immigration raids, masked.

[Dr. Sanjay Gupta]

ICE agents, Operation Patriot Our podcast Here and Now Anytime is looking at Trump's agenda of mass deportation through the eyes of one state.

[Terry Gross]

I'm coming to Boston.

[Dr. Sanjay Gupta]

I'm bringing hell with me. Listen to the podcast here and now anytime from NPR and wbur. Here at Life Kit, we take advice seriously.

[Terry Gross]

We bring you evidence based recommendations. And to do that, we talk with researchers and experts on all sorts of topics because we have the same questions.

[Dr. Sanjay Gupta]

You do, like what's really in my shampoo?

[Terry Gross]

Or should I let my kid quit soccer?

[Dr. Sanjay Gupta]

Or what should I do with my savings in uncertain economic times? You can listen to NPR's Life Kit in the NPR app or wherever you get your podcasts.