Tools to Reduce & Manage Pain | Dr. Sean Mackey

1. 0:00 – 2:11

   Dr. Sean Mackey

   1. AHAndrew Huberman0:00

      (uptempo music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Sean Mackey. Dr. Sean Mackey is a medical doctor, that is, he treats patients, as well as a PhD, meaning he runs a laboratory. He is the chief of the division of pain medicine and a professor of both anesthesiology and neurology at Stanford University School of Medicine. Today, we discuss, what is pain? Most of us are familiar with the notion of pain from having a physical injury or some sort of chronic pain or a headache. Today, Dr. Mackey makes clear what the origins of pain are, both in the nervous system and outside the nervous system. That is, the interactions between the brain and the body that give rise to this thing that we call pain. Indeed, we discuss the critical link between physical pain and emotional pain, and how altering one's perception of emotional or physical pain can often change the other. We also discuss some of the changes in the nervous system that occur when we experience pain, and how that can give rise to chronic pain.If

2. 2:11 – 6:13

   Sponsors: AeroPress, Levels & BetterHelp

   1. AHAndrew Huberman6:02

      you'd like to try BetterHelp, go to betterhelp.com/huberman to get 10% off your first month. Again, that's betterhelp.com/huberman. And now for my discussion with Dr. Sean Mackey.

3. 6:13 – 13:05

   Pain, Unique Experiences, Chronic Pain

   1. AHAndrew Huberman6:13

      Dr. Mackey, welcome.

   2. SMDr. Sean Mackey6:15

      Oh, it's a pleasure to be here. Thank you.

   3. AHAndrew Huberman6:17

      Yeah, this is a long time coming. We're colleagues at Stanford, and I'm familiar-

   4. SMDr. Sean Mackey6:22

      Yeah.

   5. AHAndrew Huberman6:22

      ... with your work, but today, we're going to take a pretty broad and deep survey of this thing called pain. So I'll just start off very simply and ask, what is pain?

   6. SMDr. Sean Mackey6:34

      Pain is this complex and subjective experience that serves a crucial role for all of us to keep us away from injury or harm. It is both a sensory and an emotional experience, and I think that gets lost on people that includes this emotional component to it, and it is incredibly individual. And we'll get more into that hopefully as time goes by that, you know, your pain is different from my pain and is different from everybody else's. It takes an incredible toll on society when it goes chronic, when it becomes persistent to the tune of about 100 million Americans, and at last count, about a half a trillion dollars a year in medical expenses, uh, so an astounding problem we're facing in society and one that's only getting worse. And I'm hoping during the course of this discussion that we can kind of break down a little bit of the foundation of pain and kind of build it back up because unfortunately, uh, in society, there's a lot of misunderstanding about what pain is. And I think, uh, hopefully we can build that foundation and then layer on some, some useful treatments and useful options for people.

   7. AHAndrew Huberman7:51

      I'm glad you pointed out this link between the sensory and the emotional experience. Every once in a while, I'll pull something or I'll have a, you know, like a kink in my neck or my back, and it, uh, fortunately for me, it resolves pretty quickly. But I notice that when I'm experiencing that kind of pain that I become slightly more irritable, perhaps much more irritable depending on who you ask, and that everything becomes more challenging. Thinking is harder. Sleeping is harder, concentrating on anything besides pain. It's, it's a, um, it's as if something's nagging from the inside, and so that raises the, the next question that I have, which is, is pain something that's in our brain, in our body, or both?

   8. SMDr. Sean Mackey8:36

      It's clearly in our brain. And can I take a moment to kind of lay a little foundation for some of that to help clear up some of the mystery-

   9. AHAndrew Huberman8:45

      Please.

   10. SMDr. Sean Mackey8:46

       ... of pain? We know that pain, most pain all starts with some stimulus, whether it be that kink in your neck or your shoulder from working out or turning the wrong way, and what's going on there, uh, in your body is not pain. What's going on is that, uh, there are sensors in our skin, our soft tissue, and our deep tissues called nociceptors. And these nociceptors are sensing elements, and they sense different types of stimuli. They can sense temperature, uh, heat, cold. They sense pressure. They can sense pH changes due to, for instance, inflammation that may occur from, uh, any, uh, something going on in your neck or your shoulder. Those sense signals up nerve fiber types, and the two that we, we refer to are A delta and C fibers. One transmits very fast. It's responsible for that, you know, sharp jolt of pain that goes to your brain when we, uh, you know, step on a tack or put our hand on a hot stove. And there's another fiber called a C fiber which is much slower and responsible for that dull, achy pain. Now, these signals, they go to the spinal cord, lie up and down our, uh, from our head down to our, uh, our back. And they're, they're shaped. They're changed a little bit. They then are sent up to the brain, and it's once they hit the brain and they converge with this magical mystery set of nerves in the brain that it becomes the experience of pain. And if there's one key message I'd like to get to the audience is that what goes on out here, what goes on in your shoulder, in your neck is not pain. That's nociception. Those are electrical signals, electrochemical impulses being transmitted, and that is to be distinguished from what becomes the subjective experience of pain that you have. And why it's critical is that our brain serves so many functions of emotions, cognitions, uh, memory, action. All of that shapes those signals coming in from our body to create your unique experience of pain that's different from everybody else's. And I think that's important to know because we are frequently left with this notion of this one-to-one concordance between the stimulus and the experience of pain. You know, Rene Descartes, that French, uh, philosopher, I think 17th century, um, was the one who first postulated this idea of this direct linkage between the body and our actions and the stimulus and the response, and it's wrong. And unfortunately, even in medical care, we have this biomedical model that still is perpetuating this idea of a one-to-one relationship. And that's a critically important point to get across, in large part because frequently as humans, we tend to project onto others our own experiences of pain, and when we see somebody who's got an injury or something else going on, we immediately put that on them. And that has also been a problem.... a-- with many people suffering in chronic pain, which is often viewed as the invisible disease.

   11. AHAndrew Huberman12:13

       So when you say we put that on them, you mean when somebody reports being in pain, we have a hard time understanding what they're-- are experiencing because it's going to be very different than the way that we experience pain. Conversely, if somebody's in pain, they tend to assume that people are experiencing pain the way that they are. Do I have that right?

   12. SMDr. Sean Mackey12:32

       You have it perfectly right, and it actually, if I can build on that, gets worse because sometimes you have conditions like fibromyalgia, that maybe we'll get into, where outwardly, visibly you don't see anything wrong. We're used to thinking of pain as a fractured, you know, bone, as a- a swollen ankle. We see that and then we're like, "Okay. Well, you've got pain. You've got legitimate pain." Whereas this invisible disease of chronic pain, frequently you don't have something outwardly that you're seeing, but we bring in our own history of pain and we put that on other people.

4. 13:05 – 16:15

   Pain & the Brain

   1. SMDr. Sean Mackey13:05

   2. AHAndrew Huberman13:05

      I have a question that's somewhat mechanistic, but we'll keep it accessible to anybody regardless of their background. So you mentioned the nociceptors are in the body and everywhere in the body and on the surface of the body to be able to detect certain kinds of stimuli, and then those signals are sent up into the brain and the brain creates this subjective experience that we call pain. Is there a dedicated set of areas in the brain that are something akin to like a pain pathway? And the reason I ask this is that for, you know, for vision, for hearing, for touch, we probably all experience those somewhat differently. Your perception of red is probably a little different than my perception of red. We don't know for sure-

   3. SMDr. Sean Mackey13:44

      Okay.

   4. AHAndrew Huberman13:44

      ... but experiments support that idea. But there's a major difference between people experiencing the same thing differently according to a- like a mysterious mechanism in the brain as opposed to like a- an area in the brain that we can look and say, like, "Hey, like- like that's where pain is, uh, represented. That's where all these- these inputs from the body are put together to create this thing that we call pain." Um, like is there an area of the- the thalamus, a structure in the middle of the brain, that takes incoming sensory information that we could say, "Oh, that's the pain pathway"? Is there a part of our neocortex, the outer shell of the- the brain more or less, um, beneath the skull but nonetheless on the outer portion of the human brain, that we could say, "Oh, that's where pain exists," or is it a distributed phenomenon?

   5. SMDr. Sean Mackey14:28

      Yeah. That's a great question, and, you know, 'cause we'd all love if there was a pain center in the brain that we could just go knock out, but it's not that simple. And in part because pain is such a conserved phenomenon, it- it is there, it is so wonderful because it is so terrible, unless it goes wrong. But when you knock out one pathway going to the brain, there's others there that will carry that system forward and you'll still experience pain and it's there to keep us all alive. Now, to get to your point, no, there's not one pain brain area. It is thought to be more of a distributed network of different brain systems. We, at one point in time, called it the pain matrix, which represented areas such as, uh, the insular cortex, the cingulate cortex, the amygdala, a number of these brain regions that all subserve different functions. We're moving away from that because it seems like every year or so we pick up another region of the brain that's contributing to this network that subserves some additional function, some nuanced layer to it. That said, we have been able to identify some common signatures, common brain networks, that seem to represent the experience of pain, and this is where the development of brain-based biomarkers has come in. And this is some of the work that I've done starting, gosh, well over a dozen years ago and, uh, others have been, uh, building on. And what we're finding is that there does seem to be this- this conserved region, set of, uh, distributed regions, that do represent the experience of pain.

5. 16:15 – 22:46

   Treating Pain, Medications: NSAIDs & Analgesics

   1. SMDr. Sean Mackey16:15

   2. AHAndrew Huberman16:15

      So when somebody takes a so-called painkiller, let- let's take a, uh, typical over-the-counter painkiller like a ibuprofen or acetaminophen to, uh, lessen pain of some kind-

   3. SMDr. Sean Mackey16:27

      Yeah.

   4. AHAndrew Huberman16:28

      ... where is that drug or drugs acting? Is it in the body or is it at the level of the brain or both?

   5. SMDr. Sean Mackey16:36

      Yeah, and this is where some of the challenges we get into with language because technically NSAIDs, nonsteroidal anti-inflammatory drugs like ibuprofen, like, uh, Naprosyn, they're actually not analgesics. They're not technically painkillers.

   6. AHAndrew Huberman16:51

      So an analgesic is the descriptor for a, quote unquote, "painkiller"?

   7. SMDr. Sean Mackey16:55

      Yeah. There- that would be more correct, like an opioid would be- would fit into that category.

   8. AHAndrew Huberman17:00

      Mm-hmm.

   9. SMDr. Sean Mackey17:01

      The NSAIDs are anti-inflammatory drugs. They're also- there's another- this is a technical term, they're antihyperalgesic drugs, and so one of the things that happens after an injury is that we get sensitization of the area that's injured, and it's a beautiful thing because it sends a message to us to protect it. Um, what the NSAIDs do is they reduce some of that sensitization out in the periphery and then back in the spinal cord and in the brain. But they don't actually- so for instance, I was gonna say try this at home but probably not, you can, um, in a normal situation, you know, hit your hand with a fork, measure the amount of pain. Now go take an NSAID like ibuprofen. If you hit your hand with that same fork, there'll be no difference.

   10. AHAndrew Huberman17:51

       Folks, please don't do that experiment.

   11. SMDr. Sean Mackey17:52

       Don't do that at home, please.

   12. AHAndrew Huberman17:54

       Yes, yeah, or any-

   13. SMDr. Sean Mackey17:55

       Or to your neighbor. (laughs)

   14. AHAndrew Huberman17:55

       Or anywhere for that matter. Or anywhere for that matter. But you're describing pain and the local inflammation response and the hyperalgesia, the increase in pain in that general area, as something very adaptive, very important. So it raises the question-... what is the threshold for saying that somebody should treat their pain, reduce their pain? I mean, you know, any time I've done, um, you know, surgeries on animals, which I don't do anymore in the laboratory but we used to, you know, you would give them painkillers post-operatively. I've had surgeries before, I had painkillers post-operatively, although I don't like taking them, I don't like the way they make my brain feel. And so, uh, but w- we of course know that if you increase the dose of any pain medication too much, then that animal, or a human, can potentially injure themselves worse or not protect that injured area. So i- it raises a, a whole set of sort of medical, ethical, but also just purely biological questions. How do you set the threshold for yes, blunt pain, versus no, allow the pain to be there as an adaptive way of protecting yourself and healing? Presumably the inflammation is part of the healing process too. And, as you mentioned before, pain is so subjective and it's different between all of us. I mean, how do we decide, uh, whether or not it's a good or bad idea to blunt that pain?

   15. SMDr. Sean Mackey19:14

       Yeah. I think the, the, the threshold is when it's impacting your quality of life and your ability to take care of the activities of daily living, engage with family, friends, go to work. And that, that serves kind of a, your, your threshold for, you know, whether it's reasonable to, to take a medication or not. There's a lot of controversy in this space right now. It used to be we all recommended just NSAIDs for any type of acute injury. Ibuprofen, Naprosyn-

   16. AHAndrew Huberman19:41

       So NSAID is non-steroid anti-inflammatory drugs, is that right?

   17. SMDr. Sean Mackey19:43

       Indeed.

   18. AHAndrew Huberman19:44

       Could it, could we maybe list off a few of those? So I mentioned ibuprofen, acetaminophen, so sometimes referred to as, you know, the classic Advil, Tylenol. We won't throw out name brands there but what are some others? Naproxen is in that family.

   19. SMDr. Sean Mackey19:56

       Naproxen is another one. Toradol or ketorolac is another one. The two over-the-counter NSAIDs, the prototypical over-the-counter ones are ibuprofen and Naprosyn. Those are the ones you can buy over the counter without a prescription. Uh, Tylenol actually has a slightly different mechanism of injury but, you know, still fits in that same general class. It tends to be more centrally acting, ibu- uh, Tylenol or acetaminophen. But taking-

   20. AHAndrew Huberman20:22

       When you say centrally, you mean brain?

   21. SMDr. Sean Mackey20:23

       Brain.

   22. AHAndrew Huberman20:24

       Brain, yeah.

   23. SMDr. Sean Mackey20:24

       Thank you. Thank you, brain.

   24. AHAndrew Huberman20:25

       And, and, uh, is aspirin considered an NSAID? I don't believe-

   25. SMDr. Sean Mackey20:28

       Yeah.

   26. AHAndrew Huberman20:28

       Oh, it is.

   27. SMDr. Sean Mackey20:28

       Aspirin would fit into that category of basically a COX, uh, cyclooxygenase inhibitor. This is one of the, the chemical mediators that gets released during injury, and that chemical, uh, substance has a tendency to wind up or amplify the nociceptors, so that after an injury you note that you're more sensitive there. After a sunburn, you end up having more sensitization. That is what we refer to as peripheral sensitization, because it's out in the periphery, we're winding up or amplifying the response. Uh, aspirin, NSAIDs in general, will reduce that inflammation. They're anti, um, hyperalgesic. And, uh, pardon again the jargony terms that we use-

   28. AHAndrew Huberman21:17

       Mm-hmm. That's all right.

   29. SMDr. Sean Mackey21:17

       ... but hopefully it's coming across. But, but, you know, to your point, you don't want to, for instance, let's imagine you have a fractured ankle. You don't want to be reaching for a very potent opioid just so that you can continue walking on a fractured ankle that you haven't gotten evaluated by a clinician and perhaps casted. That wouldn't be safe. Those are rather extreme examples. You know, we get into those debates, right, in professional sports where, you know, they, they send the person back out on the field with a broken bone, you know, having, uh, given them a- an injection or something. I'm, I'm hoping that doesn't go on anymore but, uh-

   30. AHAndrew Huberman22:00

       Oh, I'm sure it goes on.
6. 22:46 – 28:51

   Inflammation, Pain & Recovery; Ibuprofen, Naprosyn & Aspirin

   1. SMDr. Sean Mackey22:47

   2. AHAndrew Huberman22:47

      Going a little bit deeper into mechanism, because I think it's gonna serve us well now and going forward, you mentioned the NSAIDs and, um, this, uh, C-O-X, COX is one of, it's a, is it in the family of prostaglandins?

   3. SMDr. Sean Mackey22:58

      Yeah.

   4. AHAndrew Huberman22:58

      Can we talk about prostaglandins? Because I think there are a lot of people nowadays, we hear about inflammation.

   5. SMDr. Sean Mackey23:02

      Yeah.

   6. AHAndrew Huberman23:03

      You know, inflammation's bad, inflammation's bad, but, you know, one of the things that we talk about a lot on this podcast-

   7. SMDr. Sean Mackey23:08

      Yeah.

   8. AHAndrew Huberman23:08

      ... is the fact that, you know, cortisol isn't bad, inflammation isn't bad.

   9. SMDr. Sean Mackey23:12

      Yeah.

   10. AHAndrew Huberman23:12

       These things serve a, an important biological role. So the prostaglandins seem to be one of the main ways that our immune system, uh, responds to a physical or chemical injury and, and creates inflammation. And that, as you said, that inflammation sensitizes an area, makes it literally more sensitive.

   11. SMDr. Sean Mackey23:27

       Yeah.

   12. AHAndrew Huberman23:28

       And then we introduce these drugs that, um, to restore normal functioning and living. Could we establish like what normal functioning is? I mean, for instance, if we make this really concrete, could we say, "Well, if you can sleep, fall asleep at night and stay asleep, or perhaps go back to sleep after you've woken up in the middle of the night, then, well, you heal during sleep, and so, you know, take as little painkiller as possible but enough that still lets you sleep well at night." Is that a sort of normal functioning?

   13. SMDr. Sean Mackey24:01

       (laughs) I, yeah.

   14. AHAndrew Huberman24:02

       Because when I have a kink in my neck, I don't wanna do much of anything. I try but it's really frustrating. So what is, I mean, as a physician, how, and as a patient, how do we determine normal functioning?

   15. SMDr. Sean Mackey24:13

       Yeah. And you're getting into the nuance, the complexity of this problem, because we've been talking about NSAIDs, the ibuprofens and Naprosyns, and...... as I said early on, we used to just give these out all the time. But then the research comes out and shows that by blocking inflammation, by blocking that, we may be blocking the normal healing process, and so we've seen delays in fracture repair. We've been seeing delays in tissue repair. And so now you've got on one hand a medication that may help with pain, help you improve function. You've got on the other hand something you're taking that may delay the process. Where do you draw the line? As a physician, my approach is really basically what you said. It's balancing the fact that if you're not sleeping at night, you're not gonna heal and you're not going to be able to do what you need to do the next day. And if taking an NSAID helps you sleep and helps you, uh, engage with what you need to do, take it at the lowest dose that you can get away with.

   16. AHAndrew Huberman25:20

       I've heard before that NSAIDs should be taken no more than once every six hours. People alternate different types of NSAIDs-

   17. SMDr. Sean Mackey25:28

       Oh, yeah.

   18. AHAndrew Huberman25:28

       ... every three hours. That's usually to try and reduce fever, another situation where an adaptive response fever, you know, people go out of their way to block it, right?

   19. SMDr. Sean Mackey25:35

       Yeah.

   20. AHAndrew Huberman25:35

       Prevent the brain from cooking. But again, opens up the same set of issues, and so I'm wondering if somebody has some pain that makes, you know, moving about frustrating and it's, and it's difficult but, you know, they can sleep at night reasonably well, maybe not as well as they normally do, would your suggestion to that person, if their goal is to heal as quickly as possible, to just not take anything?

   21. SMDr. Sean Mackey25:57

       Yeah. So we've got a lot more data on the benefits of NSAIDs, this class of medication reducing pain than we have data, uh, showing the bad consequences of it. And so we're still needing more data on the whole healing message. I think that a lot of the orthopedic surgeons out there prefer people not to be on NSAIDs after, for instance, a total hip replacement, a total knee replacement, because I think that's pretty clear. But that's not what we're talking about right now. So one of the other interesting things about NSAIDs, like we mentioned ibuprofen and Naprosyn, huge individual variability around those. So personally, ibuprofen is not very effective for me. Naprosyn is. For others, it may be just exactly the opposite. So there's value in rotating them and finding out which works best for your particular situation. You mentioned the timing of it. Ibuprofen is typically given no more than three times a day. It's got a short half-life. Naprosyn, twice a day. What's critical, I need to give this message, is in both situations make sure that you have food in your stomach, make sure you're not taking it on an empty stomach, make sure you're drinking plenty of fluids. And if you've got any, um, GI issues, if you've got any bleeding issues, if you've got kidney issues, if you've got heart issues, talk to your doc. Talk to your clinician before you embark on this, because these medications do have side effects and adverse consequences in vulnerable people.

   22. AHAndrew Huberman27:32

       And what about aspirin? I've heard that aspirin can benefit heart health, so I take a baby aspirin every day, and if I have a pain that is just too intense for normal functioning, as we're defining it, then I'll increase that, um, dose of aspirin. And I just assume aspirin is the healthiest NSAID for me because, well, it's also good for heart health and it's killing pain in those instances as opposed to taking anything else. Is my logic flawed? And if it is, feel free to tell me. (laughs)

   23. SMDr. Sean Mackey27:56

       No. For, for you, your logic is perfect, and that's where it gets to the individual person. And for a lot of people, that model would work as well. So baby aspirin, 81 milligrams a day acts as an anti-platelet agent, it helps, you know, here even though we're getting controversy over the role of baby aspirin if you dive into the current literature.

   24. AHAndrew Huberman28:15

       Wait, even baby aspirin's-

   25. SMDr. Sean Mackey28:16

       Even-

   26. AHAndrew Huberman28:16

       ... controversial?

   27. SMDr. Sean Mackey28:17

       Even baby aspirin these days.

   28. AHAndrew Huberman28:19

       Oh my goodness.

   29. SMDr. Sean Mackey28:19

       And now what they're doing with, with the data is d- defining age ranges when they say, "Baby aspirin, yes, baby aspirin, no." And so, you know, we're learning a lot more about that. I still take a baby aspirin.

   30. AHAndrew Huberman28:32

       Every day?
7. 28:51 – 30:19

   Sponsor: AG1

   1. SMDr. Sean Mackey28:52

   2. AHAndrew Huberman28:52

      I'd like to take a brief moment and thank one of our sponsors, and that's AG1. AG1 is a vitamin mineral probiotic drink that also contains adaptogens. I started taking AG1 way back in 2012, and the reason I started taking it and the reason I still take it every day is that it ensures that I meet all of my quotas for vitamins and minerals, and it ensures that I get enough prebiotic and probiotic to support gut health. Now, gut health is something that over the last 10 years we realized is not just important for the health of our gut, but also for our immune system and for the production of neurotransmitters and neuromodulators, things like dopamine and serotonin. In other words, gut health is critical for proper brain functioning. Now, of course, I strive to consume healthy whole foods for the majority of my nutritional intake every single day, but there are a number of things in AG1 including specific micro-nutrients that are hard to get from whole foods, or at least in sufficient quantities. So AG1 allows me to get the vitamins and minerals that I need, probiotics, prebiotics, the adaptogens, and critical micro-nutrients. So any time somebody asks me if they were to take just one supplement what that supplement should be, I tell them, "AG1," because AG1 supports so many different systems within the body that are involved in mental health, physical health, and performance. To try AG1, go to drinkag1.com/huberman and you'll get a year's supply of vitamin D3K2 and five free travel packs of AG1. Again, that's drinkag1.com/huberman.

8. 30:19 – 32:34

   Caffeine, NSAIDs, Tylenol

   1. AHAndrew Huberman30:19

      I promise we won't go into every medication in such detail, bu- but these are the most commonly used over-the-counter-... treatments for pain as far as I know. Um, are there any, um, issues with, you know, people who drink caffeine who then are taking these drugs? Or, like, what are some of the, uh, the, uh, interactions that these things can have? As far as I know, caffeine actually touches into the prostaglandin pathway, doesn't it?

   2. SMDr. Sean Mackey30:42

      Yes.

   3. AHAndrew Huberman30:42

      Yeah.

   4. SMDr. Sean Mackey30:42

      And that's where, you know, caffeine can be used effectively for headaches, for migraines, and, uh, it can help potentiate, uh, the analgesic response. Uh, some people get, uh, stomach irritation though with caffeine, so just, again, mind that you take an NSAID with, uh, a lot of coffee, uh, have some food in your stomach.

   5. AHAndrew Huberman31:02

      Mm-hmm.

   6. SMDr. Sean Mackey31:03

      You know, you brought up earlier acetaminophen or Tylenol. Tylenol doesn't have the same side effect or adverse event profile that the NSAIDs do, so Tylenol is safe on the stomach. Um, where you need to be careful about Tylenol is not to exceed 4,000 milligrams or four grams per day in divided doses. So two extra-strength Tylenol done four times a day for many people is safe. Some say two grams, some say four grams. The key here is around your liver. So if you've got good liver function, if you're not abusing alcohol, that's a general rule of thumb that you can use for Tylenol. Um, but it's not gonna upset your stomach. There are versions of the NSAIDs that we refer to as COX-2 inhibitors, they're very selective, like celecoxib, that is, uh, less irritating on the stomach. That's by prescription only though. But you can think of it as working very much the same as the naproxen and the ibuprofen. So talk with your clinician, you know, to, to try to tease those apart. If you have problems in your stomach with the NSAIDs and they're really effective for you, you can be given other types of medications that help block or reduce the GI issues associated with the NSAIDs.

   7. AHAndrew Huberman32:32

      Very useful information. Thank you.

9. 32:34 – 38:56

   Pain & Touch, Gate Control Theory

   1. AHAndrew Huberman32:34

      Here we're talking about chemical interventions to the pain process. What about mechanical interventions? So I was taught in my basic neuroscience about, I think it's Melzack and Wall's gate theory of pain.

   2. SMDr. Sean Mackey32:47

      Oh, yes.

   3. AHAndrew Huberman32:47

      Do I have this right? Where, uh, you know, we all have this instinctual response. Animals have it too, right? If they, uh, you bump your knee or your toe that you grab it and you kind of rub it, and that that rubbing response is actually contributing to the activation of a neural pathway that does indeed reduce the pain through a legitimate neural inhibition. And tell me if this is still considered correct and then I'll let you, um, uh, elaborate on it. But I think that there's an opportunity for us to also talk more generally or for you to educate us more generally on the, the mechanistic interventions for pain, like, um, maybe massage above or below the site of pain, maybe acupuncture. Um, so again, there will be chemical consequences of any mechanical intervention, right, as we know, because that's the language of the nervous system, electricity and chemicals. But as opposed to taking a drug, you can imagine using manual, um, stimulation or rubbing around it or, or perhaps we can also talk about heat and cold. So could we explore that space a bit?

   4. SMDr. Sean Mackey33:45

      Absolutely. And first, you're right, so, uh, in, in your first part. Uh, Pack- uh, Patrick Wall, Ron Melzack, luminaries in the field of pain back in the '60s, uh, defined the gate control theory of pain. And one of the things to build on the story that we talked about with nociceptors going to the spinal cor- signals going to the spinal cord, heading up to the brain where the perception of pain occurs, that's not where the story ends. It turns out there are pathways that come down from the brain, down from the brain to the spinal cord that act in an inhibitory role, and we'll build on those also. From the periphery, we've got also fibers called touch fibers. These are the ones where they get activated with light touch, stroking. They're referred to as A-beta fibers. They're fast conducting. They head back to the spinal cord and they make some connections with those nociceptive fibers. So with that gr- grounding, imagine what you said, your, you hit your thumb with a hammer, you, um, uh, you bang something on an extremity. Um, what is the first thing you do when you hit your thumb with a hammer? Uh, some people rub it.

   5. AHAndrew Huberman35:04

      I s- yell.

   6. SMDr. Sean Mackey35:05

      Some people swear, and it turns out there are studies that show that swearing works.

   7. AHAndrew Huberman35:09

      Really?

   8. SMDr. Sean Mackey35:10

      Swearing reduces pain.

   9. AHAndrew Huberman35:11

      Better than, uh, than using non-explicative, uh-

   10. SMDr. Sean Mackey35:16

       Yes.

   11. AHAndrew Huberman35:16

       ... loud vocalizations?

   12. SMDr. Sean Mackey35:17

       Yes. Swearing works. I don't know why, but, uh, there's been a, it, it caught some press when that paper came out, and, you know, I don't re- I'm not giving carte blanche. We're not saying everybody can go out and swear every time they're in pain.

   13. AHAndrew Huberman35:29

       Well, you- they can, but they'll have to bear the consequences on-

   14. SMDr. Sean Mackey35:31

       Thank you.

   15. AHAndrew Huberman35:31

       ... an individual basis.

   16. SMDr. Sean Mackey35:32

       Thank you.

   17. AHAndrew Huberman35:33

       We're not r- We're, we're absolving ourselves of any responsibility.

   18. SMDr. Sean Mackey35:36

       (laughs)

   19. AHAndrew Huberman35:36

       (laughs) Right.

   20. SMDr. Sean Mackey35:37

       So, uh, rubbing, uh, shaking is another one-

   21. AHAndrew Huberman35:40

       Mm-hmm.

   22. SMDr. Sean Mackey35:40

       ... which basically is activating those touch fibers.

   23. AHAndrew Huberman35:43

       Oh, it is?

   24. SMDr. Sean Mackey35:43

       Putting a-

   25. AHAndrew Huberman35:43

       'Cause I do that.

   26. SMDr. Sean Mackey35:44

       Yeah.

   27. AHAndrew Huberman35:44

       Ah, ah, you know, yeah.

   28. SMDr. Sean Mackey35:45

       Everybody does that. Everybody does that. Running it under water, which, you know, it doesn't matter whether, you know, in this case, it's hot or it's cold water, but it's the running of the water underneath it.

   29. AHAndrew Huberman35:55

       Mm-hmm.

   30. SMDr. Sean Mackey35:56

       And what is it doing? We all think it's reducing the stimulus out here, and it is not.
10. 38:56 – 44:53

    Pain Threshold, Gender

    1. AHAndrew Huberman38:56

       What explains different pain thresholds? I could imagine it could be any or all of the locations that we've been discussing-

    2. SMDr. Sean Mackey39:03

       Yeah.

    3. AHAndrew Huberman39:03

       ... and it could be the context as well, right? If you're, um, you know, I've heard before, and I don't know if this is true, that if you have a lot of adrenaline, epinephrine in your system, that your threshold for pain goes way, way up. There's probably a chemical basis for that, and maybe it's all, you know, um, anecdote, but, um, certainly people have different thresholds for pain. I, for instance, do not have a high pain threshold, but I've noticed I have a very quick pain response. So if I stub my toe, it feels like the most painful thing I could possibly experience, but then it's gone very quickly. So it's like a quick inflection and then down. Other people I know, uh, we've never done the experiment. I think I'd see them stub their toe and they're like, "Ah." And then, you know, ten minutes later, they're still feeling the ache. So-

    4. SMDr. Sean Mackey39:51

       Yeah.

    5. AHAndrew Huberman39:51

       ... whose pain threshold is higher? It's a, depends on how you define pain threshold. So how do we define pain threshold? What determines pain threshold? And I guess the six million dollar question, are there different pain thresholds between men and women as it relates to the whole story about childbirth being very painful and that women-

    6. SMDr. Sean Mackey40:13

       (laughs) Yeah.

    7. AHAndrew Huberman40:13

       ... quote unquote "have higher pain thresholds"?

    8. SMDr. Sean Mackey40:14

       Thank God for women.

    9. AHAndrew Huberman40:15

       I just, I just sent you about ten questions.

    10. SMDr. Sean Mackey40:17

        Yeah.

    11. AHAndrew Huberman40:17

        So forgive me.

    12. SMDr. Sean Mackey40:18

        Yeah. Um...

    13. AHAndrew Huberman40:20

        So what is pain threshold?

    14. SMDr. Sean Mackey40:21

        Yeah, no, it, it, it's a, it's a great place to start, and maybe, I don't know if you want to circle back around at some point to the heat and cold to finish up-

    15. AHAndrew Huberman40:29

        Yes.

    16. SMDr. Sean Mackey40:29

        ... the mechanical. But let me-

    17. AHAndrew Huberman40:31

        Yeah, forgive me. Oh-

    18. SMDr. Sean Mackey40:31

        No, no, no. You're, let me answer your, get to your pain threshold. So, the pain threshold is, uh, that stimulus intensity that results in the onset of the experience of pain, the first onset of the experience of pain. So, you know, when you turn up the heat, it's, it's not when it's warm, it's not when it's just hot. It's when the heat becomes the perception of pain, like, when it becomes painfully hot, at that point in time.

    19. AHAndrew Huberman41:03

        Mm-hmm.

    20. SMDr. Sean Mackey41:03

        The same works for cold. You mentioned some of the distinction between your experiences of pain to a stimulus and your body's, and that's normal. That first onset of pain, again, those are those fast fibers, those A-delta fibers, boom, right to your brain. Those are the protective ones that when we put our hand on a hot stove, we immediately jerk it back. We don't even have a conscious perception yet that we did that, and then it's a moment later when the C fibers are getting up to the brain and the other A-delta fibers are converging into conscious areas of brain that we're like, "Oh, wow, that stove is really hot." And the C fibers, in particular, are converging on more emotional regions in the brain that are conveying an unpleasantness to that experience. You don't like it, you, and you don't want it to happen again, which is why it encodes memories. So you only had to do that once as a child. Now, getting into the, the pain thresholds. You asked one of the other questions is, do men and women have different pain, um, thresholds? Uh, the answer, the short answer is yes. This has been established, and I want to be careful here, uh, with saying a couple things. One is, in general, uh, men have, uh, higher pain thresholds to things like heat stimulus than women. And w- what people have to also, though, understand-... as scientists, we make a big deal out of small differences, right? You know, what we do is we take a group of people, in this case, men and women, and we apply the same, uh, thermal stimulus to them, and we draw averages. The average man has this stimulus, the average woman has this stimulus, and we say, "Well, women have a little bit more sensitivity to that heat stimulus." And so we then go into the press and we say, uh, "Men are tougher than women." That's a terrible statement.

    21. AHAndrew Huberman43:07

        Right, because the tough part is a subjective label, right? I mean, it, it, it gets to a whole bunch of different issues around the adaptive role of pain, right? I mean, I mean-

    22. SMDr. Sean Mackey43:18

        Yeah.

    23. AHAndrew Huberman43:18

        ... one could argue that if your threshold for pain is lower, that yours, it serves a more adaptive function, right?

    24. SMDr. Sean Mackey43:25

        It's-

    25. AHAndrew Huberman43:25

        Fewer injuries, et cetera. I mean, I guess it gets into the implications of what we mean by, quote unquote, "tougher."

    26. SMDr. Sean Mackey43:30

        It does, but it also misses, I think, the big point, which is people are not averages. So what I mean by that is while the average for a woman may be somewhat less than a man, if you look at the distribution of the curves, they highly overlap, meaning the individual variability within men and within women is much greater than the difference between men and women. There's plenty of women on that curve that have much greater heat, uh, thresholds than men do.

    27. AHAndrew Huberman44:08

        Mm-hmm.

    28. SMDr. Sean Mackey44:08

        But when you pool things, you end up with that difference. Unfortunately, when things are picked up and you want a quick soundbite out of it, that's what it gets distilled down to. So-

    29. AHAndrew Huberman44:18

        So it's not unlike height, for that matter. I mean, there are a lot of women that are taller than men.

    30. SMDr. Sean Mackey44:22

        That's exactly it.
11. 44:53 – 53:20

    Pain in Children, Pain Modulation (Pain Inhibits Pain)

    1. SMDr. Sean Mackey44:53

       There's a lot of things that play into changes in pain thresholds. How much... And this is where the brain comes in because, you know, much of the nociception, much of the signals that we're, um, transducing, we're transmitting, you know, in many of us it's very much the same. It's, when it gets to the brain, now it's shaped, and it's shaped by things such as, um, your beliefs about that stimulus, your expectations around it, how much anxiety you're having at the moment.

    2. AHAndrew Huberman45:30

       Does increased anxiety increase one's perceived pain?

    3. SMDr. Sean Mackey45:34

       Yes.

    4. AHAndrew Huberman45:34

       Okay.

    5. SMDr. Sean Mackey45:35

       Yeah, it does. Um, your early life experiences with this. So if you had traumatic experiences in the past, that alters brain circuits.

    6. AHAndrew Huberman45:46

       Can I interject a question?

    7. SMDr. Sean Mackey45:47

       Yeah.

    8. AHAndrew Huberman45:48

       If one was told, "Just suck it up a lot," or if one whimpered or cursed when they, uh, hurt themselves, if they were told, um, you know, "Don't be a wuss. Don't be a wimp," do we know whether or not that increases or decreases the subjective feeling of pain later? I could imagine it going either way. I could imagine-

    9. SMDr. Sean Mackey46:08

       Yeah.

    10. AHAndrew Huberman46:08

        ... the kid that was told "Don't be a wuss" when they cried as a consequence of expressing pain or an experience of pain secretly feeling more pain because they aren't able to express the emotionality around the pain. But that if we just look from the outside, we say, "Wow, they're, like, pretty tough adult," right? Because they're not, um, crying out in pain.

    11. SMDr. Sean Mackey46:30

        Yeah.

    12. AHAndrew Huberman46:30

        So do we have any... Are there any experiments that have explored that?

    13. SMDr. Sean Mackey46:33

        I don't know. You're getting into... This is a good point, getting into, um, uh, pediatric pain and, you know, if there's been experiments in that space. I stay mainly in the adult area. And my experience with raising a child is an N of one with one son. Um-

    14. AHAndrew Huberman46:49

        He's done great.

    15. SMDr. Sean Mackey46:50

        Thank you. I-

    16. AHAndrew Huberman46:50

        I happen to know him very well. He's a, he's, he's what you call a, a great example of highly successful reproduction.

    17. SMDr. Sean Mackey46:58

        (laughs) .

    18. AHAndrew Huberman46:58

        So...

    19. SMDr. Sean Mackey46:59

        You know, it's a, what do they say? It's better to be lucky than good. Uh, so-

    20. AHAndrew Huberman47:03

        I'm sure, I'm sure there was a lot involved, so don't, don't discount-

    21. SMDr. Sean Mackey47:06

        But-

    22. AHAndrew Huberman47:06

        Don't, uh, don't discard any credit. Yeah.

    23. SMDr. Sean Mackey47:08

        Thank you.

    24. AHAndrew Huberman47:09

        Yeah.

    25. SMDr. Sean Mackey47:09

        Thank you. Um, you know, my approach with Ian was not to say ju- you know, necessarily "Suck it up," but I would, uh, you know, make light of it. I'd, I'd have fun with it, and uh, I would kind of laugh, and I'm like, "Way to go, buddy." Uh, and I would find he would often laugh, you know? So I think a lot of it is the cues they're taking off the parents. You know, and again, this is, this is just my one event parent is if they see you freaking out, kid's going to freak out too. Um, but does there get to be a point where you're ignoring your child or your loved one's painful issue? Yeah, now you're getting into some maladaptive, some bad space where I think it's sending that person the wrong message.

    26. AHAndrew Huberman47:53

        Mm-hmm.

    27. SMDr. Sean Mackey47:54

        And they may very well have problems later on.

    28. AHAndrew Huberman47:58

        I will tell just a very brief anecdote. When I was growing up, I observed a total of zero children and friends who, you know, cried out in pain or complained of pain who were told, you know, um, "That was an inappropriate response." Um, sometimes I might have heard parents say, you know, "Come on, just suck it up," or like, or, "Rub it, you'll be okay," that kind of thing. But once, and only once, we had some friends, I won't tell you (laughs) wh- what country they were from, but they, they lived not far from, um, where both Ian and I grew up, since we grew up near one another. And I'll never forget that the younger brother of a friend of mine ran over to the father. He had cut his thumb on the band saw-... and it wasn't particularly deep, but he was crying in pain. And the father wrapped it, picked up his chin, and smacked him across the face, and said, "Don't ever do that again."

    29. SMDr. Sean Mackey48:52

        (laughs)

    30. AHAndrew Huberman48:52

        And so what I think he was doing was compounding the, the lesson about the saw-
12. 53:20 – 59:53

    Tool: Heat, Cold & Pain; Changing Pain Threshold

    1. AHAndrew Huberman53:20

       physiological stimuli in terms of their ability to ameliorate, to help pain? Uh, because, of course, if you get things hot enough or you get them cold enough, you can create pain with heat or cold. But let's assume-

    2. SMDr. Sean Mackey53:30

       Yeah.

    3. AHAndrew Huberman53:30

       ... we're not getting to that level of heat or cold, and one is in pain. Um, you know, when I was a kid, we had a hot water bottle that for times when we were sick with something, but sometimes, you know, if, if I felt an ache on the side, I'd put some hot water in the hot water bottle-

    4. SMDr. Sean Mackey53:45

       Mm-hmm.

    5. AHAndrew Huberman53:45

       ... lie on that thing, watch some cartoons, I definitely felt better.

    6. SMDr. Sean Mackey53:48

       Sure, sure. Well, putting aside the contemporary controversies over the mechanisms you described, which are, I think, very real and need to be sorted out, traditionally, historically, we tend to think of applying cold for the first 48 hours or so after an acute injury and then heat thereafter. Cold has some really cool effects. Cold, uh, reduces inflammation, so it reduces some of the release of those inflammatory chemicals. We talk about prostaglandins, cytokines, histamines, um, other chemokines, all these fancy terms for substances that sensitize the primary nociceptor. And it reduces the release of those and it reduces inflammation. Another cool thing often not appreciated is nerves don't fire as fast when they're cold. And so if you've got nociceptors that are firing-... and you put cold, it's slowing the number of signals coming up and by definition, it's reducing the p- the, the, ultimately, the pain you're experiencing. Now, heat, heat has an obvious effect of increasing blood flow. It's going to help, uh, relax muscles and get blood into those muscles, and that's probably why you were putting that hot water bottle on. Um, and it just darn feels good.

    7. AHAndrew Huberman55:11

       Mm-hmm.

    8. SMDr. Sean Mackey55:12

       And so, what, what do I tell people, you know? In part, I tell people, "Use w- whichever works best for them." Um, I find there's huge individual variability in whether people like heat or like cold, and within reason, uh, they're safe. What do I mean, within reason? Don't go putting an ice pack on an extremity for two hours. You know, you'll get a frostbite. So, you know, take care with that.

    9. AHAndrew Huberman55:43

       How cold should one make the point of their body that's in pain, assuming, of course, that they're not gonna give themselves frostbit? Meaning, do you want to numb the area? You know, get past that point where it's a little bit painful and then the, you know, basically, you're shutting down some neural pathways and you don't feel anything there. It's numb and then you let the blood flow return when you remove the cold pack. Is that-

    10. SMDr. Sean Mackey56:05

        I mean, that's a reasonable suggestion.

    11. AHAndrew Huberman56:06

        ... is that-

    12. SMDr. Sean Mackey56:06

        Yeah.

    13. AHAndrew Huberman56:07

        All right. Well, people li- I think, will appreciate that the, um, the specifics of that because, um, you know, and of course, listeners to this podcast often are interested in whole body deliberate cold immersion, you know, cold showers, ice baths, et cetera. Most people experience those as somewhat painful as they get into them-

    14. SMDr. Sean Mackey56:24

        Yeah.

    15. AHAndrew Huberman56:25

        ... and then can experience some numbness when they get out. Is it possible to raise one's pain threshold through the regular exposure to pain in ways that are safe, such as deliberate cold exposure, assuming that one doesn't stay in too long and it's not too cold? Um, and/or through, you know, uh, we were talking about sports earlier, but just in general, like, can we raise our pain threshold so that life is less painful?

    16. SMDr. Sean Mackey56:49

        The short answer to your last question is yes. Um, the answer to your other question about, uh, extreme cold and cold exposure, which I know you have a lot of expertise and you can teach me a lot, I'm gonna stay in my wheelhouse a- 'cause I- I'm not up on the literature in that space, even in its intersection with pain. Um, it's an intriguing concept. Uh, I have to imagine that it makes sense you would get some habituation, uh, with that repeated exposure. I think one of the, the questions that would come up with, for instance, the cold exposure, and I don't know the answer to this, but it's, I'm sure s- maybe somebody out there does, is, is there cross-modality, um, changes in pain thresholds? I mean, if you expose yourself a lot to cold, does it change your heat thresholds? I don't, I would surprise, be surprised if it did.

    17. AHAndrew Huberman57:41

        Yeah, I would be, too.

    18. SMDr. Sean Mackey57:41

        Or your pressure. Um-

    19. AHAndrew Huberman57:42

        'Cause those are separate parallel pathways, right?

    20. SMDr. Sean Mackey57:44

        Yeah. Yeah. You know, there, uh, and, you know, as an aside, I hate the cold, but I do really well with the heat, you know? And so does Ian. Uh, you know, I think there's something genetic there. Uh, so, you know, I mentioned earlier around men and women and heat, uh, thresholds, and I chose that specifically, but each of these are different depending on the stimulus modality. Can you change, ultimately, your thresholds? Yeah. Where that involves is a lot of cognitive control. It's a lot of cognitive training, uh, around that space. And, uh, you know, there's, there's clearly approaches to that. People have learned that there's different manipulations around that. So, one experiment, this wasn't intended, at least I don't believe so, they were measuring, uh, heat thresholds, uh, in college students. And w- and we, we experiment a lot on students, as, as we all know. We pay them well. Um, and what they found is that when, they're studying guys, studying dudes, when there was an attractive woman who was delivering the stimulus, the thresholds were higher because the guys did not wanna look like a wuss in front of this attractive young woman. And that's been pretty well-established. So, the experimenter, their gender, uh, plays a big role in that.

    21. AHAndrew Huberman59:16

        Has the reverse experiment also been done?

    22. SMDr. Sean Mackey59:18

        I don't, I don't know. I don't know.

    23. AHAndrew Huberman59:22

        Interesting. Interesting.

    24. SMDr. Sean Mackey59:22

        Um, but getting back to your point, yes, um, I think through a number of, uh, you know, cognitive manipulations, you can ultimately, um, over time, change those thresholds. Another one, area, is exer- is movement. Exercise-

    25. AHAndrew Huberman59:40

        Mm-hmm.

    26. SMDr. Sean Mackey59:41

        ... you know, clearly changes, uh, those thresholds over time. You're probably building up, um, some increased inhibitory tone through that process.

13. 59:53 – 1:00:54

    Sponsor: InsideTracker

    1. SMDr. Sean Mackey59:53

    2. AHAndrew Huberman59:53

       I'd like to take a quick break and thank our sponsor, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. Now, I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. Now, a major problem with a lot of blood tests out there, however, is that you get information back about metabolic factors, lipids, and hormones and so forth, but you don't know what to do with that information. With InsideTracker, they make it very easy because they have a personalized platform that allows you to see the levels of all those things, metabolic factors, lipids, hormones, et cetera, but it gives you specific directives that you can follow that relate to nutrition, behavioral modifications, supplements, et cetera, that can help you bring those numbers into the ranges that are optimal for you. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman.One

14. 1:00:54 – 1:08:29

    Tools: Psychology, Mindfulness-Based Stress Reduction, Catastrophizing

    1. AHAndrew Huberman1:00:54

       thing I'm fascinated by in the whole mindfulness space-

    2. SMDr. Sean Mackey1:00:58

       Yeah.

    3. AHAndrew Huberman1:00:58

       ... uh, is this idea of whether or not under conditions of stress, or in this case pain, whether or not the most adaptive mindset, assuming it's not a tissue-damaging level of pain, would be to think about something else, distract oneself from the pain, or conversely, whether or not one should, quote-unquote, "go into the pain." So for people who have chronic pain, maybe it's in a, a small area of the body that experiences chronic pain, uh, pain quite often, aka chronic pain, or maybe it's whole body pain. I, I don't think it really matters for the question I'm asking. And people are trying to develop some cognitive ways, so what we call as neuroscientists, you and I, top-down mechanisms for thinking like, "Okay, I'm gonna distract myself from the pain. I'm gonna focus on other things I really enjoy," or rather, "I'm going to really go into the pain, meet the pain and realize," I don't know, somehow that it's not as bad, like, uh, somehow there's a... And again, this becomes very opaque, right? We don't really know what we're talking about when we, when we do these sorts of protocols. But those sorts of things are out there in the mindfulness space, and I think, um, I certainly take mindfulness seriously as, as an intervention. But what always bothers me about those sorts of interventions is that they lack the specificity and the granularity, and there's no kind of mechanistic logic to explain them.

    4. SMDr. Sean Mackey1:02:21

       Yeah.

    5. AHAndrew Huberman1:02:22

       So what, what are your thoughts on, on meeting the pain versus distracting oneself from the pain?

    6. SMDr. Sean Mackey1:02:27

       Let's break that down 'cause there's two concepts there as you alluded to, and they're both effective, and they both work differently. So one is attentional distraction, where you are distracting yourself from the thing that is causing pain. Clearly works in a lot of people. And that's why one of the strategies that we recommend for patients, for people living with pain is to engage in distracting activities. Read a book, um, uh, go for a walk, um, spend time with friends and family, in particular, and the community, and work to get your mind off of pain. What we've learned is i- that attentional distraction engages specific brain networks. They tend to be some of the outer layer of brain networks in your prefrontal cortex, some in your cingulate cortex, um, and other regions which are clearly involved with distraction. It's not necessarily that distraction is gonna completely eliminate one's pain, but it can reduce it, uh, significantly. And this is why the, the biggest problem with distraction from a time of the day is at night. It's when people are trying to sleep. 'Cause during the daytime, you can read that book, you can spend time with friends and family, but people with chronic pain that have it 24/7, you can't distract yourself at night when you're trying to get into a relaxed state and fall asleep. And that's why sleep is such a big issue for people with chronic pain. So attentional distraction, it, it works. Distraction works. Now what you said, I mean, the second piece, you said kind of, "Let's meet the pain," if you will. And there's different approaches to meeting the pain. One approach that you invoked with mindfulness is addressing the pain from a non-judgmental, accepting manner. "I'm aware the pain is there. I am not gonna judge it. I'm not going to put a value on it's bad, it's good, or anything. I'm just gonna note its presence." And that has been shown to work as well. In fact, actually, when Jon Kabat-Zinn originally developed mindfulness-based stress reduction, people with low back pain. Plenty of studies have shown that it works. I've completed just some recent studies in MBSR, uh, as well, and we're diving deeply into the data. So it's this non-judgmental acceptance, if you will, of the pain.

    7. AHAndrew Huberman1:05:08

       Sorry, MBSR is the acronym for-

    8. SMDr. Sean Mackey1:05:10

       M- m- Mindfulness-based stress reduction.

    9. AHAndrew Huberman1:05:13

       Mm-hmm.

    10. SMDr. Sean Mackey1:05:14

        MBSR, (laughs) everybody should do MBSR. Let me be clear. I have no financial relationship with any of this, by the way, but mindfulness-based stress reduction has been shown effective for anxiety, for depression, for pain, just about everything. I think they should put it into all the schools. Uh, it's, it's a great skill to learn. No side effects. Takes a little bit of time to learn it. And, uh, it can be, in some people, effective and helpful for pain. And that's the key that we're gonna keep coming back to is some of these things work for some of the people some of the time. There's a third aspect of meeting the pain, and that is more of a direct cognitive reframing about the meaning of the pain. Now, you're coming at the pain, and you have, um, an approach. You're making effort on what you're thinking of the pain. Is that pain damaging, threatening, harmful, or do you view it as, "Yeah, it hurts, but it's not harming me"? That is a critical, critical aspect of pain management, and that is, serves as a foundation for something called cognitive behavioral therapy. The, the cool thing about a number of these is that there's actually different neural circuits engaged with these different approaches, and, um, I think the key that we have to figure out, and this is where research is going, is which approach works for which person under which circumstance.

    11. AHAndrew Huberman1:07:04

        So interesting. Uh, something you said about understanding the pain but not, um, over-interpreting or catastrophizing the pain seems important. Knowing the difference between being hurt or feeling hurt versus being injured has been something that's been important to me. I've been involved in sports, uh, where clearly pain was involved. It's like, "I'm hurt, but am I injured?" That's the first question, you know? Like, I've rolled an ankle, I'm like, "Uh-oh." You know? It's like, "I'm limping. This hurts. Am I injured?" Meaning, am I gonna be back at it in an hour, tomorrow? Versus, (clicks tongue) I've broken bones and it's, uh, you know... I ha- uh, you know, I have great empathy for anybody that does. Like, when you're injured, you feel the snap and you know you're out for a while in some cases. Um, so I think knowing the difference between being hurt and being injured is something that's kind of that key moment. And it, for me, it's always been experienced as a moment of anxiety after feeling pain, especially in a sport. So you're like, "Uh-oh." You're like, "Am I a- am I gonna have to take two weeks off? Or is this just pain?" So I think for people to be able to recognize when pain is reporting an injury versus when pain is just reporting a temporary sensation is really important. And perhaps also for psychological hurt versus psychological injury. I mean, that gets to some larger context themes these days of somebody says something, it upsets us. Are we hurt or are we injured? Right? You know, I think it gets very murky.

    12. SMDr. Sean Mackey1:08:28

        It does.

    13. AHAndrew Huberman1:08:28

        So,

15. 1:08:29 – 1:12:38

    Tool: Hurt vs. Harmed?, Chronic Pain

    1. AHAndrew Huberman1:08:29

       how does one determine if they are hurt versus injured? And then maybe we could even stretch into the psychological realm. Neither of us are psychologists, but it sounds like so much of what you do represents the, the bridge from the body into the mind.

    2. SMDr. Sean Mackey1:08:43

       Yeah.

    3. AHAndrew Huberman1:08:43

       And so it'd be remiss if we didn't talk about emotional pain as well.

    4. SMDr. Sean Mackey1:08:47

       Yeah. So what you just said, you're spot, you're spot on, Andrew. In that, one of the key messages, the key, you know, Mackey's Tips for Pain Management is to understand the distinction between hurt versus harm.

    5. AHAndrew Huberman1:09:03

       Mm-hmm. I like that better, yeah.

    6. SMDr. Sean Mackey1:09:05

       Hurt versus harm.

    7. AHAndrew Huberman1:09:05

       Mm-hmm.

    8. SMDr. Sean Mackey1:09:07

       Critical, absolutely critical. Let me, allow me to illustrate with, um, a patient I saw. Won't name names. Some time ago. Guy was in his 40s, a master's level tennis player. Tennis is his life. He's, works as some executive somewhere, but he lives for tennis. Comes hobbling in on crutches, sits down, and he's got pain in his foot, and he was told not to put pressure on his foot because he's got this injury and it's gonna be worse. And this has been going on now for months. And he's now depressed 'cause he can't play tennis. Tennis is his life. This guy's life is tennis. So I examine this guy, and it turns out what he has is something called a Morton's neuroma. And a Morton's neuroma is a fibrous thickening of tissue around the nerves that go to your toes, and it gets to be like these bundled tissue nerves, and it's really painful. Um, it's very painful. But it's not causing harm. There's no harm there. It's really painful. So I explain this to the guy, and he looks at me with like, this lightbulb goes off, and he's like, "You mean I can play tennis?" And I'm like, "Yeah, guy, you can go play all the tennis you want. It's just gonna hurt." He got up, he left the crutches in the exam office, and he walked away. Now, that's an extreme example. I don't want people, please, to think that that kind of thing occurs all the time. It doesn't. Um, chronic pain conditions are often incredibly complicated and need much more than, you know, a 45-minute or 60-minute education session and, you know, back to the tennis court. He still had pain in his foot, by the way, but he could play. But that gives that example of addressing that fear and the anxiety ar- around that, that issue. And I think that's what we first have to learn is does that pain that we're experiencing represent something that is harming us, that's something that we either need to seek, uh, medical attention now or sometime soon, and whether does continued activity worsen the tissue injury or not? In my world, where I'm caring mostly for people with chronic pain, we've moved beyond the tissue healing. By definition, by one of the definitions for chronic pain is that the pain persists beyond the time of tissue healing. So in many of our sessions, our times, we're educating people hurt versus harm. If it's back pain, we, we evaluate the spine. We make sure is the spine stable? Is there anything sinister causing damage? In most of the cases, it's not. And we help people understand that distinction. Critical, critical for people. And yet at the same time, you don't wanna just ignore something that is a real medical issue that's getting worse and needs medical attention, and that's where the complexity of all this comes in. Did I answer your question?

    9. AHAndrew Huberman1:12:31

       Yeah, beautifully. I think this distinction between hurt versus harmed is so important for people to hear. Um,

16. 1:12:38 – 1:20:43

    Emotional Pain, Anger, Medication

    1. AHAndrew Huberman1:12:38

       perhaps you're willing to expand a little bit in terms of the psychological hurt versus harmed. I mean, I'm not asking you to comment on, um, societal or generational shifts, but, you know, we'd be avoiding the obvious if we didn't say that in the last, um, really 10 to 15 years, there's been a pretty dramatic shift in terms of how society at large interprets emotional pain, right? People hearing things or seeing things and the idea that emotional pain could-... be related to physical pain or at least similar enough to it that people's emotional pain is valid, right? And it- I, if anything, I'm here to validate the fact that emotional pain is valid like any other pain, except it is different because it becomes very hard to point to a specific kind of threshold, we're using that word a lot today, but I think it's appropriate here, threshold between hurt and harm. Whereas if I tell you that my left foot hurts, which it did a lot in high school, and then you took an X-ray of my foot in high school, you'd say, "Your foot's broken," because it was broken a lot in high school. And that's harmed. Uh, I mean, to continue to do what I was doing to break it in the first place, I was harm, clearly going to harm myself worse, so I had to d- I had to heal up. But when it comes to psychological pain, you know, psychiatry has all these thresholds for normal functioning versus abnormal functioning, are you sleeping well? Normal relationship? And on and on. We don't want to go there 'cause that's not our place, but how do you, when you see patients, how do you take into account the level or the thresholds for their emotional pain? Because that's part of your job. So I'm asking you this from the perspective of a-

    2. SMDr. Sean Mackey1:14:16

       Yeah.

    3. AHAndrew Huberman1:14:17

       ... somebody who treats pain. How do you gauge somebody's psychological pain? Is it by how intensely they vocalize their pain or does it always go back to how well or poorly their life is being managed at the level of sleep, nutrition, relationships, and so forth?

    4. SMDr. Sean Mackey1:14:32

       Yeah. Great, great set of questions. There's a lot in there. Let me first start off with something very simple. I don't try to distinguish between this notion of psychological pain, physical pain. It's pain, end of. End of. I think once I get into, or you get into this trying to distinguish is this psychological pain or psychogenic pain, which was a terrible term, or physical pain, you end up putting value judgments on people, and I don't think it serves us well when we're caring for the person in front of us. If they're in pain, I'm addressing the pain. The thing to note is, at least in people that come into our, uh, Stanford Pain Management Center, and other pain centers, is that remember pain is a sensory and emotional experience. It's all wrapped up. And so, we want to treat the whole person. Sometimes we get, we get easy, we get easy ones and we just go do a nerve block and pain goes away-

    5. AHAndrew Huberman1:15:42

       (smacks lips)

    6. SMDr. Sean Mackey1:15:42

       ... and that's simple, but usually it's much more complex where we're seeing the interaction of, uh, an e- expression of pain that includes a significant amount of anxiety, of depression. You mentioned this term catastrophizing, which we can break down if you'd like, and that's probably one of the biggest predictors, factors in, uh, in amplification of pain and worsening pain and poor treatment response is catastrophizing. Um, I try to treat the whole person and not really parcel out all this. I do, at Stanford, I u- I, I built a digital health system that captures, measures a lot of data around a patient's experience across physical, psychological, and social functioning, and we use that data to target therapies, to understand, um, how much their depressive symptoms are, anxiety, anger. Anger, big issue in pain. Huge in pain.

    7. AHAndrew Huberman1:16:46

       Does it make it worse or better?

    8. SMDr. Sean Mackey1:16:48

       Invariably it makes it worse.

    9. AHAndrew Huberman1:16:49

       Mm-hmm.

    10. SMDr. Sean Mackey1:16:50

        Yeah. And, you know, you can break anger down in a couple different categories. John Burns and others has broken it into like anger in versus anger out. I don't know if that term's familiar with you. Um, anger out, that's my father. Um, loud, loud, angry, boisterous, (banging) banging, you know, would quickly turn anything into an angry tirade. Anger out, expressive.

    11. AHAndrew Huberman1:17:16

        Yelling at the, at the news.

    12. SMDr. Sean Mackey1:17:18

        Yes.

    13. AHAndrew Huberman1:17:18

        Yelling at somebody who cuts you off in traffic.

    14. SMDr. Sean Mackey1:17:20

        Usually yelling at the man, uh, (laughs) 'cause he hated his job. Um, anger in, boiling, simmering, you know, self-contained, seething. That's anger in. Data seems to support anger in is, is worse. It's bad.

    15. AHAndrew Huberman1:17:38

        So it's not necessarily whether or not it's directed at someone external. In both cases, anger in and anger out can be directed at someone external. It's a question of whether or not it's expressed outwardly or contained inside.

    16. SMDr. Sean Mackey1:17:49

        Beautifully stated. Beautifully stated. So we cat- you know, anger, depression, anxiety, uh, we capture fatigue, sleep, and so what we try to do is, again, look at the whole person because they're not just a back if that's where they're having pain or not just a neck or a shoulder in your case. It's impacting the whole person. And we just got done talking earlier about how all of these circuits interact with each other, and so sometimes we can't just eliminate the nociception and the periphery. Sometimes we can reduce it, but what we have to do is target everything and we have to try to target all these circuits up here. And in many cases what we're doing is through education, through pain psychology, um, through physical therapy and relabi- rehabilitative approaches on top of it, and yes, the medications we have now, you know, we touched base on a few earlier, but we have over 200 medications available for pain, um, very few of them FDA approved. Uh, we tend to steal from all the other fields.

    17. AHAndrew Huberman1:18:56

        So you're talking about more than 200 medications that can be, yes, prescribed for pain, but as off-label treatments?

    18. SMDr. Sean Mackey1:19:04

        Perfectly stated. Yeah. There's only a few medications that are actually FDA approved specifically for pain. So what we, what we do...... is we borrow or steal from the psychiatrists, some of their, uh, their antidepressants, uh, which will frequently work very effectively for pain and work on those pain-related circuits in the brain. We, uh, take from the neurologists some of the anti-seizure medications because those medications, um, while reducing separately seizures, for people who don't have seizures, they work on ion channels. Um, they work on other neuromodulators that also are involved in pain circuitry. We can take from the cardiologists medications that work on the heart, anti-arrhythmia or heart rhythm drugs. They are potent sodium channel blockers, and the sodium channels, as you know, are responsible for the action potential that generates the nerve impulse signal. And so they're like an oral local anesthetic that you take. And so we, we s- we take from everybody in our field in the medications. Getting back to, to what you said, so w- just summarizing, one, I, I don't really distinguish, uh, psychological versus physical pain in my world. I, I find it better just to treat it as pain and look at the person holistically and go after all the components at once. I find that's where we get the best results, and it is typically bringing a lot of tools to bear.

17. 1:20:43 – 1:28:45

    Tool: Nutrition & Pain; Food Sensitization & Elimination Diets

    1. SMDr. Sean Mackey1:20:43

    2. AHAndrew Huberman1:20:43

       Speaking of tools to bear, what role, if any, does nutrition play in local or s- whole body pain?

    3. SMDr. Sean Mackey1:20:52

       Uh, critical, and I think we're learning more and more and more about, uh, the role of good nutrition, of healthy eating, anti-inflammatory diets, uh, avoidance of foods that are triggers, um, and an incredibly underappreciated area. Um, you know, I've had my experiences with chronic pain. Um, I developed, uh, an abdominal chronic pain problem, uh, shortly after I turned 50. I was throwing a happy hour for our pain psychologists, of all people, went to a Mexican restaurant, I won't name which one, got food poisoning. That's why I'm not naming it. Good Mexican food, bad food poisoning, and ever since that event, I can't eat anything in the onion family.

    4. AHAndrew Huberman1:21:51

       What, um, I'm familiar with onions, but what else is in the onion family?

    5. SMDr. Sean Mackey1:21:55

       Well-

    6. AHAndrew Huberman1:21:55

       I'm sure you've researched this now pretty thoroughly considering what you're describing.

    7. SMDr. Sean Mackey1:21:58

       Classic in the what we refer to as FODMAPs. You know, it's one of the FODMAPs, and I have now some issues with the others and, um, manifested by just severe, severe upper abdominal pain and, um, not many other symptoms. But, you know, it put me on this journey where, uh, severe abdominal pain, didn't know why, couldn't sleep, couldn't sleep, went, like I'd go months without having a restful night's sleep. I thought I was getting early Alzheimer's 'cause I felt like I was getting stupid. And, um, what actually benefited me was, of all things, the pandemic. Why? 'Cause what did we all do? We isolated. We started eating the same foods, and I started noticing I was feeling better when I was eating certain foods. My abdominal pain went away, and I'd start doing, as a scientist, experiments. And I finally was able to isolate and determine what the problem was. So now I have complete avoidance on that. Um, I'm a little difficult to go out to a restaurant and have dinner, but, you know-

    8. AHAndrew Huberman1:23:05

       So no onions.

    9. SMDr. Sean Mackey1:23:06

       No onions.

    10. AHAndrew Huberman1:23:06

        And what else not-

    11. SMDr. Sean Mackey1:23:07

        Shallots, chives, scallions, leeks, anything in the onion family, you know? Not allium. I'm fine with garlic. And, you know, by healthy eating, by identifying something by triggers, changed my life and r- returned to a degree of normalcy. I think the key for people is, you know, if you have s- any kind of similar issues, identify those triggers, sometimes, uh, isolation of, you know, foods or restrictions, and using a journal. And then as you learn from that, slowly build foods back into your diet.

    12. AHAndrew Huberman1:23:47

        I think it's so important for people to hear this, and thanks for sharing your personal story around this because I think that nutrition, while every physician seems to appreciate that the quality of nutrition matters, defining what quality of nutrition is is really difficult. There's still, you know, uh, avid, even we could call them rancorous debates about this, you know, vegan versus omnivore versus this, and, you know, but it sounds like this is a case where it can become very individualized. But I could imagine somebody going to their physician, and that physician not being you, and saying, "Yeah, you know, I notice that when I eat certain foods, I'm in a lot of pain," and the physician simply saying, "Well, don't eat those foods." But unless that person is a trained scientist, like not knowing how to go about doing the sorts of experiments that you did would be difficult. So-

    13. SMDr. Sean Mackey1:24:33

        Impossible.

    14. AHAndrew Huberman1:24:34

        Yeah.

    15. SMDr. Sean Mackey1:24:34

        I'm sorry. I know I interrupted you. I just wanna b-

    16. AHAndrew Huberman1:24:36

        Please.

    17. SMDr. Sean Mackey1:24:36

        ... build on that if I, if I can. One of the key things, I simplified my story, but the key thing is, is if I, if I eat onions or anything in the onion family, it's pain for two weeks.

    18. AHAndrew Huberman1:24:47

        Wow.

    19. SMDr. Sean Mackey1:24:47

        It is. So the thing is, is if you get repeated exposures, it never stops, and it gets very, very hard to figure out what it was. So it's not like you eat something, you get pain, it goes away, where, you know, we can all do that pattern recognition. Here, you have to be able to think back, "What happened two weeks ago that may have influenced it?" So it's not easy.

    20. AHAndrew Huberman1:25:13

        Well, this may be a case for-... elimination diets, which are, uh, provide they're done safely, where people restrict the number of foods they eat to a very limited number of foods, make sure they still get enough calories and macronutrients-

    21. SMDr. Sean Mackey1:25:24

        Yeah.

    22. AHAndrew Huberman1:25:24

        ... uh, th- that they need, protein, fats, and carbohydrates or what- what have you. But that by limiting the total number of foods that they eat to, like, eight or 10 basic things, then you can build things in and then explore what triggers the pain or what removes the pain. I don't s- really see any other way. I am intrigued by the onion example, even though it's a, it's a, it's your case in particular and we don't wanna extrapolate too broadly. Is there something about onions that's triggering a particular neurochemical or immune pathway? Uh, do we have any knowledge of, like, why onions would create that kind of gut pain?

    23. SMDr. Sean Mackey1:25:57

        This has been a journey I've been on now for a few years to answer this. Um, uh, one of our GI pain docs that we have come in the clinic, Linda Nguyen, sent me a paper from, I don't know, Cell or Nature that showed that after a gut infection, it can change the genetic expression related to sensitizing you to food antigens. I know I threw out a lot of jargon there. Basically, the short answer is you get an infection and your gut no longer responds properly to a normal food item. And so one explanation may be I got this infection, I was at a Mexican restaurant, a lot of onions, and I got sensitized through that infection, now subsequently to onions. You know, I saw a, uh, Stanford, uh, allergist, uh, Hannah Watford, who's awesome by the way, and, uh, after I'd had this I think figured out, and I went in and I'm like, "Well, you know, Dr. Watford, is there anything I can do for this?" And she laughed and she's like, "No, you're doing everything. It's all just avoidance." And I, thinking I was rather unique and special about this thing, I said, "You know, do you ever see this?" And she said, "Oh, yeah, I see this all the time. Every day, I see this all the time." And I said, like, "This isn't unusual." She's like, "No, I see this thing all the time." And I said-

    24. AHAndrew Huberman1:27:19

        "This thing" meaning sensitivity to onions?

    25. SMDr. Sean Mackey1:27:21

        Sensitivity to cert- no, to certain, to different- ... these different food groups and this, this thing that occurs later in life, something, an event that happens to somebody that triggers... And I said, "Well, gosh, that sounds like a public health problem." And she's like, "That's what we're debating right now in the allergy community, is whether th- this is representing more of a public health issue and is... 'Cause I'm seeing, I, Dr. Watford, am seeing increasing amounts of this, uh, as we go forward."

    26. AHAndrew Huberman1:27:51

        How interesting. Well, um, this is not a time to plug the philanthropic arm of our premium podcast, but, uh, I'm very involved in science philanthropy. Th- this sounds like an area to de- devote some funding to do, to explore how foods are impacting the local and systemic pain response.

    27. SMDr. Sean Mackey1:28:07

        Yeah.

    28. AHAndrew Huberman1:28:07

        So-

    29. SMDr. Sean Mackey1:28:08

        I, I got in, you know, so I'm running a large biomarker study to characterize people deeply, and one of the things that I wanted to put in there is microbiome characterization. Now, to be clear, that's out of my wheelhouse, but the beauty of being at Stanford and other major institutions is you can go make friends.

    30. AHAndrew Huberman1:28:24

        Yeah. Justin Sonnenburg, who's been a guest on this podcast-
18. 1:28:45 – 1:34:02

    Visceral Pain; Back, Chest & Abdominal Pain

    1. AHAndrew Huberman1:28:45

       As long as we're talking about the gut, um, let's talk about pain inside the body, because we talked about nociceptors on the surface of the body and the pain that most people, uh, immediately think of when you have a discussion about pain is, you know, pain on the surface or a broken bone or maybe hip pain or knee pain or back pain. But what about pain that resides deeper in the viscera, you know, uh, gut pain, um, irritable bowel syndrome? These things are, I'm learning, are far more c- uh, common-

    2. SMDr. Sean Mackey1:29:15

       Yeah.

    3. AHAndrew Huberman1:29:15

       ... than, um, than I knew. I'm fortunate that, um, if I have a stomach ache or a headache, it means something's wrong. I rarely get those. I've sometimes been called a, you know, have a stomach of steel, not because it's hard from the outside, um, but because I can eat pretty much anything, although I eat pretty cleanly. A lot of people write to me and ask questions on social media about irritable bowel syndrome and other forms of gut pain and viscera pain, like pain that they feel is really deep within their system. Typically, how is that sort of pain dealt with at a clinical level?

    4. SMDr. Sean Mackey1:29:47

       Absolutely. Visceral pain is a different thing than what we've been describing, uh, a lot of which is somatic pain. By the way, I'll say as an aside, I used to have a gut of steel also. I could chomp down anything, anytime, anywhere, and so, you know, there was a lot of grief and loss associated with not being able to eat certain foods, and, uh, that's also something people have to come to grips with. Um, but getting back to visceral pain, so the thing about somatic pain s- That's another term now, somatic meaning the soma, the, the, the extremity that you were alluding to is the nociceptors there, uh, very precisely localize where the stimulus, the painful stimulus is coming from. When you hit your thumb with a hammer, you know exactly where that pain occurred. With the visceral pain, what you have are very diffuse what we refer to as receptive fields. Think about y- the last time you had a stomach ache. It's not that you put your thumb right here. What you said is, "It kinda hurts like this." It's-

    5. AHAndrew Huberman1:31:00

       Your whole stomach.

    6. SMDr. Sean Mackey1:31:01

       ... whole stomach. It's because those receptive fields are very large. They're broad. They're not as well localized. And in part, the reason for that type of broad receptive field is you're not trying to get away from localized danger.So when people get stomach aches, it's often a very broad area. When you get pelvic pain, it's the same type of thing. Now, there's some fascinating stuff that occurs with visceral pain because those fibers that extend from the viscera, meaning the, the lungs, the abdomen, the pelvis, they all head into the spinal cord too. And it just so happens that they make kind of indirect c- direct connections with the same level that represents the body. So let's think about pelvic pain, for instance. You frequently will find people that say th- that have pelvic pain that will describe having lower back pain too and it's because of this visceral somatic convergence in the spinal cord. It's not that there's something going on in their back. It's that these signals that are being driven heavily from the pelvis are coming in and connecting with the same regions from the back and the convergence of that is now being perceived as pain in both. And w- we, we are seeing that more and more in the research, this viscerosomatic convergence. People have pain in their pelvis and then also over their abdomen. Um, classic one that, uh, we're aware of, we see this in the TV, the movies, and unfortunately real life are heart attacks. So the visceral fibers that subserve the heart, typically the first through the fourth thoracic region, well, those converge, um, in the spinal cord in similar regions that subserve sensation under the arm and up here. That's why people will often say they've got pain with a heart attack radiating down into their arm.

Episode duration: 2:56:41