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
Ecology 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 ultimately
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. We also of course cover different methods to reduce pain safely and those methods include behavioral tools psychological tools nutrition supplementation. And of course prescription drugs, we discuss the intimate relationship between temperature that is heat and cold and pain.
In and Pain Relief. So if you're interested in the use of heat or cold to modulate pain that conversation ought to be of interest as well. We also touch on some highly controversial topics such as opioids opioids are substance that your body naturally makes but of course many people are familiar with exogenous opioids that is opioids that are available as drugs and the so-called opioid crisis. Dr. Mackey makes very clear which specific clinical circumstances warrant the use of exhaustion has opioids with of
course a warning about their potent addictive potential and we get into a bit of discussion about where the opioid crisis and the use of opioid drugs to control pain is and is going before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however a part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's podcast. Our first sponsor is Aeropress.
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Or schedule in a very convenient way if you'd like to try better help go to better help.com huberman to get 10% off your first month. Again. That's better help.com hubermann, and now for my discussion with dr. Sean Mackey, dr. Mackie welcome. Oh, it's a pleasure to be here. Thank you. This is a long time coming. We're colleagues at Stanford, and I'm familiar 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 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 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. 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.
Back up because unfortunately in society there's a lot of misunderstanding about what pain is and I think hopefully we can build that foundation and then layer on some some useful treatments and usual options for people. I'm glad you pointed out this link between the sensory in 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 fortunately for me it was always pretty quickly, but I notice that when I'm
Anything 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 the pain. It's a it says if something's nagging from the inside and so that raises the next question that I have which is
Is pain something that's in our brain and our body or both. 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 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 in your body is not pain what's going on?
Is that there are sensors in our skin or soft tissue more deep tissues called nociceptors and these nociceptors are sensing elements and they sends different types of stimuli. They can sense temperature heat cold. They sense pressure. They can sense pH changes due to for instance inflammation that may occur from any something going on in your neck or your shoulder those send signals.
up nerve fiber types
And the two that we refer to our a Delta and C fibers one transmits very fast. It's responsible that you know sharp jolt of pain that goes to your brain when we you know, step on a tack or put her 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 by up and down our from our head down to our back and they're they're shaped their 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 and 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 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 philosopher. I think 17 century 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 a pain and when we see somebody who's got an injury or something else going on we immediately put that on them and that is also been a problem with many people suffering in chronic pain, which is often viewed as the invisible
disease. So when you say we put that on them you mean when
Somebody reports being in pain. We have a hard time understanding what their 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? You have a 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 fracture.
Heard, you know bone as 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. I have a question that 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.
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 experienced those somewhat differently. Your perception of red is probably a little different than my perception read. We don't know for sure but
experiment support that idea but
There's a major difference between people experiencing the same thing differently according to a mysterious mechanism in the brain as opposed to like a an area in the brain that we can look and say like hey look like that's where pain is represented. That's where all these these inputs from the body are put together to create this thing that we call pain. Like, is there an area of 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 brain more less beneath the skull but nonetheless on the outer portion of the human brain that we could say. Oh, that's where paintings us or is it a distributed phenomena?
Yeah, that's a great question and you know because we'd all love it. There was a pain center and 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 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 the insular cortex the cingulate cortex, the amygdala a number of these brain regions that all sub serve 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's observed some additional functions some nuanced layer to it.
That's sad.
We have been able to identify some common signatures common brain networks that seemed to represent the experience of pain and this is where the development of brain-based biomarkers is come in. And this is some of the work that I've done starting.
Gosh, well over a dozen years ago and others have been building on and what we're finding is that there does seem to be this this conserved region said of distributed regions that do represent the experience of
pain. So when somebody takes a so-called painkiller, let's take a typical over-the-counter pain killer like a ibuprofen or acetaminophen to lessen pain of some kind. Yeah. Where is that drug?
For drugs acting is it in the body or is it at the level of the brain where both?
Yeah, and this is where some of the challenges we get into with language because technically NSAIDs non-steroidal anti-inflammatory drugs like ibuprofen like Naprosyn. They're actually not analgesics. They're not technically pain killers.
So an analgesic is the descriptor for a quote-unquote
painkiller. Yeah there that would be more correct like an opioid would be would fit into that category.
The NSAIDs are anti-inflammatory drugs. They're also there's another this is a technical term their anti hyperalgesia control uggs. 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. What the NSAIDs do is they reduce some of that sensitization out in the periphery.
Periphery and then back in the spinal cord and in the brain, but they don't actually so for instance. I was going to say try this at home, but probably not you can in a normal situation, you know, hit your hand with a fork measure the amount of pain. I'll go take an NSAID like ibuprofen if you hit your hand with that same Fork, there will be no difference folks, please. Don't do don't do that at home, please. Yeah,
or art or anywhere for that matter or anywhere for that matter, but you're describing pain and the
Formation 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 anytime I've done, you know surgeries on animals, which I don't do anymore in the laboratory, but we used to you know, you would give them pain killers postoperatively. I've had surgeries before I had painkillers postoperatively, although I don't
Don't like taking them. I don't like the way they make my brain feel and so but 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 it raises 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 to and as you mentioned before pain is so subjective and it's different between all of us. I mean, how do we decide whether or not it's a good or bad idea to blunt that pain?
Yeah. I think 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 threshold for you know, whether it's reasonable to take a medication or not. It's a lot of controversy in the space right now used to be we all recommended just NSAIDs for any type of acute injury. I don't
permit a non-steroidal anti-inflammatory drugs indeed. 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 will throw out a name brands there. But what are some others naproxen
and the
There's another one toward. All our cue to row lack is another one the to over-the-counter NSAIDs the prototypical over-the-counter ones or ibuprofen and Naprosyn. Those are the ones you can buy over the counter without a prescription. 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 I be Tylenol or acetaminophen but takes a
centrally you mean brain, right? Thank you thank and brand is aspirin.
Considered an end side. I
don't yeah, I would it would fit into that category of basically a Cox cyclooxygenase inhibitor. This is one of the chemical mediators that gets released during injury and that chemical substance has a tendency to wind up or amplify the nociceptors so that after an injury, you note that you're more sensitive thereafter a sunburn you end up having more sensitization. That is what we refer to.
To as peripheral sensitization because it's out in the periphery were winding up or amplifying the response aspirin NSAIDs in general will reduce that inflammation their anti hyperalgesia.
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 given them an injection or
I'm hoping that doesn't go on anymore. But I'm sure it goes on. Okay.
Yeah, there's all sorts of other things. I get contacted all the time professional teams and athletes asking how they can get back in quicker nowadays. The big thing are these peptides that can certainly accelerate healing people are traveling out of country get stem cell injections all with all with very few randomized control trials, but I assure you that Courtside and in the locker room mainly in the locker room there corticosteroid injections their painkiller injections. I mean, it's it's not
Play it any expense. Yeah, but it's not far from that. Okay?
Yeah. Yeah. Well, you know when you're making millions of dollars a year and I get the being back on the field, but for the rest of us mere mortals. I think that's where we would want to draw a line get medical attention. If you've got an acute
injury going a little bit deeper into mechanism because I think it's going to serve us well now and going forward you mentioned the NSAIDs and this Co X Kox is one. It's a it in the family of
Prostaglandins. Yeah, we talked about prostaglandins because I think there are a lot of people nowadays we hear about inflammation. Yeah inflammations bad inflammation is bad. But you know, one of the things that we talked about a lot on this podcast is the fact that cortisol isn't bad inflammation isn't bad these things serve up an important biological role. So the prostaglandins seem to be one of the main ways that our immune system responds to a physical or chemical injury and and creates inflammation and that it as you said that inflammation sensitize the scenario makes it literally more.
Yeah, and then we introduce these drugs that 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 the night then well you heal during sleep and so, you know take as little painkillers possible but enough
That still lets you sleep. Well at night is that it sort of normal functioning because I have a kink in my neck. I don't want to 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?
Yeah, and you're getting into the Nuance the complexity of this problem because we've been talking about NSAIDs ibuprofen Saint a person's and as I said early on we used to just give these out all the time, but then the
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 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?
ouch is really basically what you said, it's balancing the fact that if you're not sleeping at night, you're not going to 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 engage with what you need to do take it at the lowest dose that you can get away with
I've heard before that ends at should be taken no more than once every six hours people alternate different types of
Sounds every 3 hours that's usually to try and reduce fever and other situation where an Adaptive response fever, you know, people go out of their way to block it right 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.
Yeah, so we've got a lot more data on the benefits of NSAIDs this class of medication reducing pain than we have data 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 at total knee replacement because I think that's pretty clear, but that's not what we're talking about right now.
One of the other interesting things about NSAIDs like we mentioned ibuprofen and a person huge individual variability around those. So personally ibuprofen is not very effective for me now percent 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 now person 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 GI issues, if you've got any bleeding issues, if you've got kidney issues, if you've got heart issues talk to your dock talk to your clinician before you embark on this because these medications
Do have side effects and adverse consequences in vulnerable people.
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 dose of aspirin and I just assumed aspirin is the healthiest and sad 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 now 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 antiplatelet 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, but even baby ask even
controversial even baby aspirin these days and now what they're doing with with the data is 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 every day. Yeah, I take a baby aspirin 8 he get to the higher doses say four times as much up around 325 milligrams or so. It's now an anti-inflammatory. It's now acting more like the ibuprofen and then a person so different mechanism of action at different doses.
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I promise we won't go into every medication in such detail. But these are the most commonly used over-the-counter treatments for pain as far as I know are there any issues with you know people who drink caffeine who then are taking these drugs are like what are some of the the interactions that these things can have as far as I know caffeine actually touches into the prostate gland and pathway, doesn't it?
Yes, and that's where you know caffeine can be used effectively for headaches for migraines and it can help potentiate the
Analgesic response some people get stomach irritation though with caffeine. So just again mind that you take an NSAID with a lot of coffee have some food in your stomach, you know, you brought up earlier acetaminophen or Tylenol. Tylenol doesn't have the same side effect or adverse event profile that the N sets do so Tylenol is safe on the stomach where you need to be careful about. Tylenol is not to exceed.
Exceed four thousand 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 to G 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, but it's
Can 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 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 now percent and the ibuprofen so talk with your clinician, you know to try to tease those apart if you have problems in your stomach
With the NSAIDs and the really effective for you. You can be given other types of medications that help block or reduce the GI issues associated with the NSAIDs
very useful information. Thank you 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 smells a can walls gate theory of pain. Do I have this right where you know, we all have this instinctual response animals have it too, right if they you bump your knee or your toe that you grab any 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
Elaborate on it, but I think that is an opportunity for us to also talk more generally or for you to educate us more generally on the mechanistic interventions for pain like maybe massage above or below the site of pain may be acupuncture. 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 stimulation or
Rubbing around it or or perhaps we can also talk about heat and cold. So we explore that space a bit.
Absolutely and first you're right. So and your first part pack Patrick Wall Ron melzack luminaries in the field of pain back in the 60s 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 cord signals go into 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 will 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 their refer to as a beta fibers there fast conducting
they had back to the spinal cord and they make some connections with those nociceptive fibers.
So with that grounding, imagine what you said your you hit your thumb with a hammer you you bang something on an extremity. What is the first thing you do when you hit your thumb with a hammer some people rub it nice yell some people swear and it turns out there are studies that show that swearing works really swearing reduces
pain better than then using non explicative. Yes loud vocalization.
Yes swearing works. I don't know why but there's been it caught some press when that paper came out. And yeah, I don't rhyme not given carte blanche. We're not saying everybody can go out and swear every time they're in
pain. Well do they can but they'll have to bear the consequences on an individual basis. We're not we're absolving ourselves about this
possibility. So robbing shaking is another one which basically is activating those touch fibers. It is putting I do that. Yeah everybody. Yeah. Everybody does.
Running it under water which you know, it doesn't matter whether you know, in this case it's hotter. It's cold water. It's the running of the water underneath it. And what is it doing? We all think it's reducing the stimulus out here and it is not at and the periphery and the periphery what's magical about that think which is so cool is you're actually changing the signals in your spinal cord way back here in the neck. This is the cheapest free version of what we refer to as neuromodulation. That's
I've been discovered you're actually by doing that you're changing things the connections back in your spinal cord and it's reducing the nociceptive signals coming in here. That's why we do it and it works it works beautifully. That's why when a kid gets there boo boo, you know parents come and rub it it works.
What about the kiss the kids sometimes all they want to kiss, you know, or a romantic partner will sometimes like injure themselves. I guess it depends on
The nature of the relationship and they'll say like, can you kiss it? Of course, you know, then you kiss it and then like they feel better. Is that purely psychological?
Well, okay, I think an important point to ground here when it comes to the experience of pain. Is that everything when we say psychological means Neuroscience for you know, you know, you know, no
forgive me. I have to be careful with with the the wording that I use
that's my fault, but it's accurate still it is psychological, but it is neuroscience.
Just I mean, they're really becoming one in the same but to answer your question. Yes by kissing it. You're activating touch fibers. We can also agree that there's a positive emotional salience its associated with that and that positive emotional salience is reducing pain, too.
What interesting a wall in melzack sometime later? There was the introduction of a device to take advantage of this called the tens device and tens is an acronym transcutaneous electrical nerve stimulation.
And what the tens device is doing and there's many versions of it now, but there are those black electrodes you put over the area and they're hooked up to wires and when you turn it on it causes a buzzing sensation and that buzzing sensation is activating those touch fibers the a beta fibers and so it's causing that neuromodulation back in the spinal cord amazing. It's cool stuff. It's
very cool. And I love that. Um,
Sighs that when we're rubbing the periphery or shaking our hand at the periphery again being the body surface away from the brain that the real mechanism of action is taking place back in the spinal cord because it really speaks to the body wide and that the circuit wide the nervous system wide nature of this thing that we call pain right? It's happening out Quantico out here in the periphery, but it's being modulated in the neck level of the spinal cord approximately and then it
It's you know being interpreted at the level of the brain.
What explains different pain thresholds I could imagine it could be any or all of the locations that we've been discussing? Yeah, and it could be the context as well. Right if you're 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 anecdote. But 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 we've never done the experiment. I think I see them stub their toe and they're like
And then 10 minutes later. They're still feeling the ache. So 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 quote-unquote have higher pain thresholds and John I just sent you about 10 questions.
Yeah, yeah, forgive me. Yeah, so what is pain
threshold? Yeah. No, 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 the mechanical but forgive me. I don't know your let me answer your get to your pain threshold. So the pain threshold is that stimulus intensity that results in the onset of the experience of paying 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.
Hot it's when the heat becomes the perception of pain like when it becomes painfully hot at that point in time the same works for cold. You mentioned some of the distinction between your experiences of pain to a stimulus and your buddies 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
And 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 were 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 and 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 pain threshold you asked one of the other questions is do men and women have different pain thresholds. The answer the short answer is yes. This has been established and I want to be careful here was saying a couple things one is in general men have a higher pain thresholds to things like heat stimulus then women and what people have to also
stand 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 applied the same 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 men are tougher than women. That's a terrible statement, right? Because the tough part is a subjective label, right? I
mean it it gets to a whole bunch of different.
Issues around the Adaptive role of pain right? I mean, I mean could one could argue that if your threshold for pain is lower that yours serves a more adaptive function. It's fewer injuries Etc. I mean, I guess it gets into the implications of what we mean by quote-unquote tougher.
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 but there's plenty of women on that curve that have much greater heat thresholds than men do but when you pull things you end up with that
Prince unfortunately when things are picked up and you want a quick sound bite out of it, that's what it gets distilled down to so it's
not unlike height for that matter there. A lot of women that are taller than
men that's exactly it. But on average men are taller than women on average and I would say within this area of pain threshold differences. It's even closer. It's even tighter.
You know, it would be I'm making this up the equivalent. I think the average height of a woman is at 53 54 the average height of a man 59 510. This is Imagining the average height being, you know 56 for a woman in 58 for a man. You know, it's not a huge difference.
There's a lot of things that play into changes in pain thresholds.
How much in this is where the brain comes in? Because you know much of the nociception much of the signals that were 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 shaped by things such as your beliefs about that stimulus your expectations around it how much anxiety you're having at the moment.
Does increased anxiety increase ones perceived
pain? Yes. Okay. Yeah, it does your early life experiences with this. So if you had traumatic experiences in the past that alters brain circuits,
can I interject a question? If one was told just suck it up a lot or if one whimpered or cursed when they hurt themselves if they were told you 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 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 like pretty tough adult right because they're not crying out in pain.
So do
we have any are there any experiments that have explored
that I don't know you're getting and this is a good point getting into 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 1 with one son
son. Great. Thank you happen to know him very well. He's what you call a great example of Highly Successful reproduction.
So, you know a say, what do they say it?
Better to be lucky than good.
So I'm sure there was a lot involved. So don't don't put count. It. Don't don't discard any
credit. Thank you. Thank you, you know my Approach with Ian was not to say just you know necessarily suck it up, but I would you know make light of it I'd have fun with it and I would kind of laughs and I'm like wait to go buddy and I would find he would often laugh, you know, so I think a lot of it is the ques they're taking off the parents, you know, and again this is this is just my one of
And parent is if they see you freaking out kids going to freak out too. But does there get to be a point where you're ignoring your child or your loved ones painful issue? Yeah. Now you're getting into some maladaptive some bad space where I think it's sending that person the wrong message and they may very well have problems later on.
I will tell you just a very brief anecdote when I was growing up. I observed a total of zero children and friends who you'll cried out in pain or complained of pain who were told, you know, that was an inappropriate response. 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 what country they were from but they they lived.
Far from 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 bandsaw 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. And so what I think he was doing was compounding the the lesson about the saw. Yeah, but clearly had no regard for the pain that the injury probably cause. No, I haven't followed up with that kid. Yeah. I think we can all agree that by today's standards that would be considered abusive parenting or perhaps, you know, one could say that was you know on the far extreme of a response, but I'll never
At that and I went home and I told my mom and she said oh, yeah, when I was growing up that was actually a more frequent response to kids hurting them spell themselves, especially boys. Yeah, and so things have really changed in terms of how we react to children in pain. But the reason I find this interesting is that ultimately what we're talking about is, how should we interpret our
own pain? Yeah. I can I can I make a commentary about that scenario and I want to bring in another Neuroscience concept that that Dad may have been
Doing inadvertently and that's something called conditioned pain modulation. So there's another cool phenomenon and in pain that pain inhibits pain.
So what I mean by that is when you were you know, this guy this kid but our yourself growing up. Did you ever walk up to your buddy? That's how you know, my my arm really hurts. You know, I injured it the other day and what did what did your buddy do they'd stomp on your foot and you say why the heck did you do
that you and I must have grown up with the same from yeah,
and and they table now doesn't doesn't your arm feel better. I'll be like well, yeah it does and yeah, I did grow up with those friends. I tell this story to some people and I
Times just get the wide eyes like they did what?
Yeah, we are not making recommendations here.
We're not making recommendation, but it's a real phenomenon. It was described by lab hours late 70s 78 or something like that in rodent models initially. And what happens is that when you engage a nociceptors stimulus or a painful stimulus in a site distal different from where the primary pain is, it engages a brainstem circuit that has descending Pathways to the
spinal cord and inhibits pain amazing pain inhibits pain, it works. It also sought to have some contributions from higher brain centers. We call this whole phenomena bars called this phenomenon diffuse noxious inhibitory control or zdenek the human version of this is called conditioned pain modulation why I bring this up not only to help explain that father's actions somehow. I don't think that he was thinking all my kids got a pain.
You know hand or finger he cut himself. I'm going to slap him off the side of the head. He'll feel better. I don't think that's what was going through his
head. I want to make him feel worse. So he didn't go near the bandsaw without being more cautious
but it probably did reduce the pain a little bit to some extent now where it's he is and maybe we'll get into it later with chronic pain is in some chronic painful conditions the CPM or the did neck doesn't work like fibromyalgia being one, so,
Pain inhibits pain is another Neuroscience concept related to pain. That's rather cool.
Well, and I'm sorry I missed your question till could you repeat know your went you
answer the question and expanded on a completely surprising and far more interesting way than I ever anticipated. So thank you. I'm betting that 98% of people listening to this including myself have never heard that pain inhibits pain. Incredible. Let's go back to heat and cold. We briefly touched on heat. But let's talk about the use of quote-unquote therapeutic heat or therapeutic.
Old a cold pack for you know, a you know a bruise that really aches or maybe even a break or a sprain or heat, you know, the in the world of sport physio cold is now heavily debated localized cold is heavily debated, you know, you get people saying things I don't know. If this is true that you know, it creates a sludging of the of the fluids trying to head in and out of the injury. So cold is not as good as heat heat allows for the
Inclusion and removal of waste products and they you know, they're all sorts of Just So Stories that people make up some of which might be true. I don't know but what do we know about heat and cold as physiological stimuli in terms of their ability to ameliorate to help pain? Because of course if you get things hot enough you get them cold enough, you can create pain with heat or cold but let's assume we're not getting to that level of heat or cold and one is in pain. You know, when I was a kid, we had a hot water bottle.
Bottle that four times when we were sick or something, but sometimes you know, if I felt an ache on the side, I'd put some hot water in the hot water bottle lie on that thing watch some cartoons. I definitely felt better.
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.
Max called reduces inflammation. So it reduces some of the release of those inflammatory chemicals. We talked about prostaglandins cytokines histamines other chemokines all these fancy terms for substances that sensitize the primary no susceptor and it reduces the release of those and it reduces inflammation. Another cool thing often not appreciated is nerves don't fire.
ER 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 its reducing the the the ultimately the pain you're experiencing now heat heat has an obvious effect of increasing blood flow. It's going to help relax muscles and get blood into those muscles and that's probably why you're putting that hot water bottle on.
And it just darn feels good. And so what what do I tell people you know in part I tell people use whichever works best for them. I find there's huge individual variability and whether people like heat or like cold and within reason, 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.
How cold should one make the point of their body that's in pain assuming of course that they're not going to give themselves frostbite. Meaning. Do you want to numb the area? You'll 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 I mean, it's a reasonable
suggestion. Okay? Yeah. All right. Well people
I think we appreciate that the specifics of that because you know, and of course listeners this podcast often are interested in whole body deliberate cold immersion, you know cold showers ice baths Etc. Most people experience those at somewhat painful as they get into them. Yeah and then can experience some numbness when they get out. Is it possible to raise ones pain threshold through the regular exposure to paint in ways that are safe such as deliberate cold exposure assuming that one doesn't stay in too long. It's
not too cold and or through, you know, we're talking about sports earlier, but just in general like can we raise our pain threshold? So that life is less painful
the short answer to your last question is yes the answer to your other question about extreme cold and cold exposure, which I know you have a lot of expertise and you can teach me a lot. I'm going to stay in my wheelhouse at because I'm not up on the literature in that space even in its.
Action with pain. It's an intriguing concept. I have to imagine that it makes sense. You would get some habituation 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 maybe somebody out there does is there cross modality changes in pain thresholds. I mean if you expose yourself a lot too cold
Does it change your heat threshold? I don't I would surprise be surprised if it did. Yeah, I would wear your pressure. Those are separate parallel Pathways. Yeah, yeah, you know there and you know as an aside, I hate the cold but I do really well with the heat, you know, and so does Ian, you know, I think there's something genetic there. So, you know, I mentioned earlier around men and women and heat thresholds and I chose that specifically but each of these are different depending on the
Millis modality
Can you change ultimately your thresholds? Yeah where that involves is a lot of cognitive control. It's a lot of cognitive training around that space and you know, there's there's clearly approaches to that.
People have learned that there's different manipulations around that so one experiment is wasn't intended at least I don't believe so they were measuring heat thresholds and college students and we experiment a lot on students as we all know, we pay them well 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 want to look like a wuss in front of this attractive young woman and that's been pretty well established. So the experimenter their gender plays a big role in that
has the reverse experiment also been done.
I don't I don't know. I don't know interesting but getting back to your point the yes, I think through a number of you know cognitive.
Manipulations you can ultimately overtime change those thresholds. Another one area is exercise movement exercise.
You know clearly changes those thresholds over time. You were probably building up some increased inhibitory tone through that process.
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Those numbers into the ranges that are optimal for you. If you'd like to try inside tracker, you can go to inside tracker.com huberman to get 20% off any of inside trackers plans. Again, that's inside tracker.com huberman. One thing I'm fascinated by in the whole mindfulness space. Yeah, 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 small area of the body that experience is chronic pain pain quite often AK chronic pain, or maybe it's whole body pain. I don't think it really matters for the question. I'm asking and people are trying to develop some cognitive way. So
What we call as neuroscientist you and I top-down mechanisms for things like okay. I'm going to distract myself from the pain. I'm going to 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 I somehow there's a and again this becomes a 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 I certainly take mine.
A seriously 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 out of mechanistic logic to explain them. So what are your thoughts on on meeting the pain versus distracting oneself from the pain?
Let's break that down because 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 go for a walk spend time with friends and family in particular in the community and work to get your mind off of pain what we've
Learned is that attentional distraction engages specific brain networks. They tend to be some of the outer layer of brain networks and your prefrontal cortex some in your cingulate cortex and other regions, which are clearly involved with distraction. It's not necessarily the distraction is going to completely eliminate ones pain, but it can reduce it significantly in this is why
The biggest problem with distraction from a time of the day. Is it night?
It's when people are trying to sleep during the daytime. You can read that book. You can spend time with friends and family, but people with chronic pain that have a 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 of the pain is there I am not going to judge it. I'm not going to put a value on it's bad. It's good or anything. I'm just going to 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 and mbsr as well and we're diving deeply into the data. So it's this non-judgmental acceptance of you will of the pain.
Sorry mbsr is the acronym for
mindfulness based stress.
Action mbsr. 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. It's it's a great skill to learn no side effects takes a little bit of time to learn it and it can be in.
Some people effective and helpful for pain and that's the key that we're going to 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 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 I think the key that we have to figure out and this is where research is going.
Thing is which approach works for which person under which
circumstance.
So interesting, it's something you said about understanding the pain but not 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 where clearly pain was involved like I'm hurt but am I injured that's the first question, you know, like I've rolled an ankle like, you know, like I'm limping this hurt in my injured meaning it.
Going to be back at it in an hour tomorrow versus a broken bones and it's you know, you know 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. So I think knowing the difference between being hurt and being injured is something that's got that key moment. And for me, it's always been experienced as a moment of anxiety after feeling pain, especially in a sports. You're like, oh like my my gonna have to take two weeks off or is this just pain so
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 or we hurt or we injured right? You know, I think it gets very murky. So how does one determine if they are hurt versus injured and then maybe we could even stretch into the psychological
Well, neither of us are psychologists, but it sounds like so much of what you do represents the bridge from the body into the mind and so be remiss if we didn't talk about emotional pain as
well. Yeah. So what you just said your spot your spot on Andrew and 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.
better versus harm critical
Absolutely critical. Let me allow me to illustrate with.
Patient I saw won't name names some time ago guys in his 40s a master's level tennis player tennis has 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 going to be worse and this has been going on now for months.
And he's now depressed because 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's gets to be like is bundled tissue nerves and it's really painful.
It's very painful.
But it's not causing harm.
There's no harm there. It's really painful. So I explained this to the guy and he looks at me with like this light bulb goes off and he's like you mean I can play tennis.
And I'm like, yeah, you can go play all the tennis shoe Juan. It's just going to 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 pleased to think that that kind of thing occurs all the time. It doesn't 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 out example of addressing that fear and the anxiety 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 something that we either need to seek a medical attention now or sometime soon and whether does continued activity.
To worsen the tissue injury or not in my world where I'm carrying. 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 were educating people hurt versus harm.
It's back pain. 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 want to 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? Yeah, beautifully. I think this distinction between hurt versus harmed is so important for people to hear 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 societal or generational shifts, but you know, we'd be avoiding the obvious if we didn't say that in the last really 10 to 15 years. There's been a pretty dramatic shift in terms of how Society at Large.
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 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 for using that word a lot today, but I think it's appropriate here threshold between hurt and harmed 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 foots broken because it was broken a lot in high school and that's harmed. I mean to continue to do what I was doing to break it in the first place. I was harmed clearly going to harm myself worse. So I had to do to heal up but when it comes to a 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 because it'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 somebody who treats pain. How do you gauge somebody 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. Yeah great great set of questions. It'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, its pain and of and of I think once I get into are you get into this?
It distinguishes a 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 10 people that come into our 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 and that's simple but usually it's much more complex where we're seeing the interaction of
An 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 an amplification of pain and worsening pain and poor treatment responses catastrophizing I try to treat the whole person and not really parcel out all this I do.
Stanford IU I've 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 how much their depressive symptoms are anxiety anger anger big issue in pain huge in pain. Does it make it worse or better? Invariably it makes it worse.
Oh, 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 terms familiar with you anger out. That's my father loud loud angry boisterous banging, you know would quickly turn anything into an angry tirade anger out
expressive yelling at the at the news. Yes yelling at somebody.
You off in traffic usually yelling at the man because he hated his job anger in boiling simmering, you know, self-contained seething that's anger n data seems to support anger and his is worse. It's
bad. 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.
Beautifully stated beautifully stated so we can't you know anger depression anxiety. 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 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 in 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 through physical therapy and real a bit 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 very few of them FDA.
Proved we tend to steal from all the other
fields. So you're talking about more than 200 medications that can be yes prescribed for pain. But as off-label treatments
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 psychiatrist some of their their antidepressants which will frequently work very effectively for pain and work.
work on those pain-related circuits in the brain
We take from the neurologist some of the anti-seizure medications because those medications while reducing separately seizures for people who don't have seizures. They work on ION channels. They work on other neuromodulators that also are involved in pain circuitry. We can take from the cardiologist medications that work on the heart anti arrhythmia our 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
take from everybody in our field in the
medications. We getting back to what you said, so
Just summarizing one. I don't really distinguish psychological versus physical pain in my world. 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.
Speaking of tools to Bear What role if any does nutrition play in local or whole body
pain critical and I think we're learning more and more and more about the role of good nutrition of healthy eating anti-inflammatory diets avoidance of foods that are triggers.
And Incredibly underappreciated area, you know, I've had my experiences with chronic pain.
I developed an abdominal chronic pain problem shortly after I turned 50. I was throwing a happy hour for our paint 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
what I'm familiar with.
Ins but what else is in the onion family? I'm sure you've researched this now pretty thoroughly considering what you're
describing classic and what we refer to as fodmaps, you know, it's one of the fodmaps and I have now some issues with the others and manifested by just severe severe abdominal pain and not many other symptoms. But you know, it put me on this journey where 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 because I felt like I was getting stupid and what actually benefited me was of all things the pandemic why because what do 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. I'm a little difficult to go out to a restaurant and have dinner
but so no onions no onions and what
else shallots chives scallions leaks anything in the onion family, you know, not a Liam. I'm fine with garlic.
And you know by healthy eating by identifying something by triggers changed my life and return to a degree of normalcy. I think the key for people is, you know, if you have any kind of similar issues identify those triggers sometimes 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. 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 quality of nutrition matters defining what quality nutrition is is really difficult. There's still you know, 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 position not being you and saying yeah, you know, I noticed 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 and possibly yeah.
I'm sorry. I know I interrupt you. I just want to at least hold on that if I if I can one of the key things I simplified my story but the key thing is is if
if I if I eat onions or anything that onion family it's pain for two weeks it is so the thing 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.
Well, this may be a case for elimination diets, which are provided they're done safely where people restrict the number of foods they eat.
A very limited number of foods, make sure they still get enough calories and macronutrients that they need protein fats and carbohydrates or what have you but that by limiting the total number of foods that they eat is like 8 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 really see any other way. I am intrigued by The Onion example, even though it's a it's your case in particular. We don't want to extrapolate to broadly is there something about onions that's triggering or
ocular neurochemical or immune pathway. Do we have any knowledge of like why onions would create that kind of gut
pain? This has been a journey. I've been on now for a few years to answer this one of our GI pain docs that we have come with Clint Linda new wind sent me a paper from a cell or nature that show that after a gut infection. It can change the genetic expression related to sensitizing you to food antigens. I know I threw
A lot of jargon. They're 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. Maybe I got this infection as at a Mexican restaurant a lot of onions and I got sensitized through that infection now subsequently to onions, you know, I saw a Stanford allergist a Hannah Watford who's awesome by the way and
After I 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 saw this isn't unusual. He's like no I see this thing all the time and I said meaning sensitivity to Heaven need a certain notice certain two 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
There this is representing more of a public health issue and is because I'm seeing eye doctor Watford him seeing increasing amounts of this as we go
forward. How interesting. Well this is not a time to plug the philanthropic arm of our premium podcast, but I'm very involved in science philanthropy at this sounds like an area to devote some funding to to explore how foods are impacting the local and systemic pain response.
Yeah. I got an A, you know, so I'm running a large.
A marker study to characterize people deeply and one of the things that I wanted to put in there as microbiome characterization now to be clear that's out of my wheelhouse but the beauty of being at Stanford and other major institutions as you can go make friends. Yeah, Justin Sonnenberg who's
been a guest on this podcast is one of the world experts on the gut microbiome. We have a few others too. So there you go. So the friendly guy, I'm sure he'll collaborate
we go we go make friends and people who understand the microbiome. We collect the samples and that's where team science is magical.
And once again the idea looking at the whole
person.
As long as we're talking about the gut 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 immediately think of when you have a discussion about pain is 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 gut pain irritable bowel syndrome. These things are I'm learning are far more.
Common, then that I knew I'm fortunate that if I have a stomach ache or a headache. I mean something's wrong. I rarely get those. I've sometimes been called the you do have a stomach of Steel not because it's hard from the outside. But because I can eat pretty much anything. Although I 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 visceral pain like pain that they feel is really deep within their system. Typically. How is
Is that sort of pain dealt with that a clinical level
absolutely visceral pain is a different thing than what we've been describing a lot of what your somatic Pain by the way. I'll say is an aside. I used to have a gut of Steel also, I could jump 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 that's also something people have to come to grips with but getting back to visceral.
And so the thing about somatic pain, so that's another term now somatic meaning the Soma the extremity that you were alluding to is the nociceptors. They're 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 you that last time you had a stomachache. It's not that you put your thumb right here. You said is hurts like this your whole stomach whole stomach. It's because those receptive fields are very large their broad. They're not as well localized and in part. The reason for that type of broad receptive field is you're not
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 had into the spinal cord, too.
And it just so happens that they make kind of indirect and 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 said 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 at the 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 and both.
And we're seeing that more and more in the research this viscera somatic convergence people have pain in their pelvis and then also over their abdomen classic one that we're aware of. We see this in the TV the movies and unfortunately real life or heart attacks. So the visceral fibers that's observe the heart typically the first through the fourth thoracic region well,
Those converge in the spinal cord and 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 the left arm. Typically the left arm. The heart is on the left side exactly after people get abdominal surgery Sometimes some blood can leak out and it'll slip underneath the diaphragm. The diaphragm is subservient.
Buy some of those neck regions 3 4 and 5 of the cervical which happens to also cover your shoulder. And so you'll get people after abdominal surgery. They said ma'am. My shoulders really hurting me Doc and what we do is we first check to see, you know, could something have happened during anise, you know during placement just make sure there's nothing wrong that frequently it's due to irritation.
That's again one of the magical Mysteries. It's so fascinating about
pain.
Seems like a good point to bring up referenced pain or is what you're describing an example of reference pain. So my understanding of reference pain is that you know what for instance. I've got a slight bulge at I think like my lumbar 34 disc or something. I had a whole body scan recently just an exploration scan because I had the opportunity not not anything serious fortunately and there's a slightly bulge dis there and every once in a while.
If I do certain movements in the gym, I'll get pain down in my right hip and sometimes going down my leg and I used to think it was sciatica because you're used to doing anything on the right back side. Okay's must be wallet induced sciatica sciatica back pocket while it and do sciatica, but what I eventually realized is that well, it's this disc bulge. It just so happens that the nerves that emit from that that region.
Branch out to a bunch of different areas. And so you think the pain is in your leg, but the issue is someplace else or and occasionally indeed. I feel the pain elsewhere in my body as well it sort of like a like a matching of regions for pain that seem unrelated is that way to think about reference pain
perfectly the the the examples also I referred to a heart attack causing referred pain or also the pelvic region associated.
With back pain as a way of referred pain what you're describing is the fact that pain doesn't have to start with an injury or stimulus in the periphery. You could damage the nerves anywhere along the way and that will be perceived as pain. We refer to that as neuropathic pain. So that's another distinction you brought up nicely good good segue into there's thought to be
Several different types or categories of pain we have been talking through much of this time about somatic pain, you know injury out here. We talked about visceral pain and when you have damage to a peripheral nerve damage injury to a peripheral nerve or the central nervous system. We refer to that as neuropathic pain, it frequently has different qualities different characteristics people will refer to it as shooting stabbing shock like burning.
It can frequently when there's a damage to a nerve or damage to certain regions of the brain be incredibly challenging to treat by the way. The good news is with that light disc bulge is the vast majority of time the discs reabsorb. Yeah. I
have to be careful to not do too much spinal flexion, like sit ups and stuff. I thought that would help but that actually doesn't strengthen the back. It was actually a symmetry between the abdominal
and the lower back muscles so is provided I do a lot of back extension type training then that bulge more or less stays in I just have to be a little little cautious not to cautious fortunately as long as we're talking about referenced pain somatic visceral and all the rest, what about associative or reference pain where it's psychological and I don't want to get too abstract here, but more and more these days I hear from people who say, you know, I
Was in this job and the job sucked or I was in this relationship and the relationship sucked and I had terrible back pain like really acute localized back pain or chronic headaches or migraines. Yeah, and then they go on vacation or they change their circumstances and lo and behold the pain goes away. Does that surprise you as an expert in
pain? Not at all. Not at all what you're you know simple simplistically.
foreign to his you know, there's people are undergoing stress and we have
we clearly know that the brain is not a passive recipient of information coming in from the body. It's a two-way street. The brain is causing Downstream consequences in the body. The brain controls are sympathetic nervous system and parasympathetic nervous system the sympathetic being the fight and flight response. It controls the tone of cortisol that's being released and we all know that in acute.
Ins rapid increases of cortisol and noradrenaline is keeps us away from the lions and tigers and bears. Oh my butt in a chronic situation and Robert sapolsky, as you know, it's Stanford has built a career around chronic stress at least in part and very bad for us. And so these chronic stressors impact the end organ the tissue
and it's real pain. It doesn't mean that we need to go get back surgery.
It means that probably we need to identify the stressors that are contributing to that and address those and will often find that in the scenarios. You outlined that the pain gets better. Some of those targets are interesting.
There's a lot of memory
associated with pain. This is where early life events occur and those early life events in injuries can sensitize us to Future.
Vulnerability, so I was in a car act bad car accident when I was 16 fortunate to walk away from it got bad whiplash.
If I get stressed a lot of my pain manifests in my neck.
For me as a pain doc. It's a signal to me. That's like go workout. Go for a walk in the forest, you know and take some time away from the computer.
Again, that's a simplistic message and my experience doesn't translate into everybody else, but I'm just validating everything that you you
said.
Let's consider the opposite scenario which is positive emotions. You've done some very nice studies exploring how being in positive relationships being in love. In fact can change our perception that is our experience of pain and probably does so it real physiological levels as you mentioned earlier psychological is physiological and vice versa. It's hard to separate the two but could you share with us?
You did in that study and what you found because I find it really interesting and it also points to the incredible power of love in how we experience life. Yeah.
Yeah. I think there's several cool things about that study that I love to share one is how it all came about so, you know us neuro science Geeks often go to the society for Neuroscience is an annual meeting and I was hanging out and sharing the room with our Terran who
studies passionate love and he and his wife study passionate love and we were having a glass or two of wine and mask in art. If you ever you know, you ever studied pain is like know I studied love and he's like if you ever studied them know I studied painting has anyone ever studied the intersection another glass of wine. No, let's do it. So we came back to Stanford and there was a young postdoc Jared younger who's now a professor at the University of Alabama and I suggested we were either going to fall flat on her face or we're going to this is going to be
Will study and Jared took this on great job. So what we did is we advertised on campus for couples in an early phase of a romantic relationship because there's a reason for choosing that in an early phase of a romantic relationship. You are deeply focused on your beloved there on your mind all the time. You feel great when you're with them you feel terrible.
When you're not with them, doesn't that just sound like an
addiction?
I mean, it's that yearning. I don't know that's it's a can be a pleasant experience
that but addictions, you know for the people who are using the substance can find it, you know in that early phase very pleasant, but it turns out that the early phase of a romantic relationship engages the same neural circuitry. He's as addiction interesting same reward circuitry all that. So we chose that
And so he said come to us and bring pictures of your beloved and bring pictures of an equally attractive acquaintance clothed. This isn't sex that we're studying the clothes and we cause them pain in the scanner and and we paid them afterwards we needed.
A control condition for this because thinking about your beloved is very attentionally demanding. Remember we talked about attentional distraction earlier. So we gave people what's called a word generation task very simply. Can you think about every sport that doesn't involve a ball?
Okay, frisbee hockey boxing boxing. Okay, that's attentionally demanding think about every vegetable that's not green and you know, so you're running through your head and we're causing you pain. It's an attentional distraction task. So we flash people pictures of their beloved cause paying flash people of their acquaintance cause pain and then distraction. Okay, what do we find? Love works?
Great love
works. Great. It was a wonderful.
Isaac it's significantly reduced people's pain and it turned out the more and love you were the more pain relief you got
when viewing the photo of the person you love.
Yes, when viewing the photo of the person you love. Now. How did we know how much in love they were? It turns out the psychologists have got scales for everything and one of them is a passionate love scale, which ask how what percentage of the day are you preoccupied thinking about your
Beloved. Oh goodness. You just sent people now off to give their Partners the passionate love scale. That's a grout how much time they're spending thinking about
them. Yeah, we had Stanford students some of them thinking about their beloved 80% of the day. I wanted to use this as a screening tool for our resident applicants because I want them focusing on patients not their beloved and that is by the way a joke that bad joke, but but
it probably is real world. We're not just talking about Stanford. I mean, oh no, but when somebody is writing you
Ripped or prescription that is or giving you advice. You might want to know if they are in a new romantic relationship.
Yeah. So the the other I thought the other cool thing about this study was attention worked also, but attention and love worked on different circuits, so attentional distraction, they worked equally well attention again worked on some of these prefrontal regions these outer cortical areas.
Love worked on more of what we classically think of is these reward-based circuits the nucleus accumbens the amygdala one of the descending brainstem regions called the substantia nigra, which is coming down from the brain through that area to the spinal cord to inhibit pain. So classic addiction Pathways classic. And so the key again message for people is different what we would think
of his psychological approaches engaging different brain circuits to reduce pain
I'll leave you with one last side note that we didn't publish on and that is Jared went back a year later. And we assess the student strength of their relationship if some it was still ongoing and he found that there was a rather High correlation between the love induced analgesia and brain activity and the caudate nucleus and in the insular with the strength of the relationship a year later it was
So we had a brain scan that was a predictor of future strength of a relationship.
Could you tell us the direction of those results? So if a new romantic partnership is creating high levels of activity in these two brain areas, you just mentioned then it is a very good predictor that the relationship will yes survive over time.
Well in this limited sample that meant that it was going to be very strong a year later understand and you know, and we
always have to put these caveats sure unpublished non-peer-reviewed. It was a fun post-hoc data analysis that I'm not sure if anybody's ever, you know, run with those kind of
things. No, but we can explore it in a playful way now and people can do with it. What they will it does sort of speak to something important though assuming that result would hold up if the same experiment we're done and you know, maybe many hundreds or thousands of people.
Sort of speaks to the idea that the activation of these addiction like circuits in the early phase of a passionate love relationship set in motion a certain number of things that create stability in that relationship which on the face of it makes sense. But we've also all heard it the opposite way of well as well which is, you know Fools Rush In or that things that start fast and Fast or things like that, but here you're talking about the early phase of passion, sir.
This interesting role in terms of analgesia alleviating pain, but also predicting some stability of the relationship over time. It's kind of interesting.
It's fascinating to talk about I you know, I feel like I have to put that caveat being that not generalize but a fun thing to talk about and it's where I think cool scientific ideas can come from for future exploration that I think that's also what's pretty neat.
I find the you know, again the different circuits for different approaches to reducing pain fascinating again that gets to the question. You asked me earlier as or one circuit and the answer is no what we have to do is figure out what is the best circuit for a particular person or set of
circuits if you're willing. I'd like to talk about opioids.
First if you could educate us on endogenous opioids the opioids that we make inside of our body that we don't that meaning. Nobody takes as a drug and then how that informs opioids that people take I mean clearly the so-called opioid crisis is a concern many people addicted to opioids people have died from taking too many opioids, but presumably some people have benefited from these opioid drugs as well. I would like to talk about that and then I'd like to also
Talk about some of the things that are adjacent to the prescription opioids things like Kratom which right now are sort of called into question as to whether or not they will continue to be legally available over the counter. So first and foremost, what are the endogenous opioids? How do they work and that I think will set the stage for the rest.
Yeah. So we all have these endogenous and careful ins and endorphins that act as painkillers.
They are analgesics. They are natural substances and all of us that get expressed. There is a certain endogenous tone to these that some have done research on here. Again, Jared did research on this and Steven Brule and others on showing that higher and dodging us opioid levels May, you know lead to less emotional reactivity. For instance. Thank God we know.
We have endogenous opioids or you know, we just couldn't handle it what chemists have figured out is how to, you know, bring in an exogenous opioids and morphine was the prototypical one from the from the poppy and since then medicinal chemists have built on variations of morphine and created other compounds some again variations on morphine. Some are purely synthetic like the oxycodone
could ask you
Shannon because I'm fascinated by the history of these things. How did or went and or when did somebody look at the puppy and then say Oh, I'm going to start eating poppies or isolating things from poppies and realize that morphine
thousands of years ago. So poppies have been used for a very long long long time. These things have been around. So this is this is old school work that's only been refined and more contemporary history.
And the whole topic of opioids is such an incredibly controversial area and I
I feel like I have to
you know, you have to understand the speaker mic in this case me my you know one's position on this. My usual Mantra is I am not pro opioid. I am not anti opioid. I Am pro patient. So I have seen opioids positively transform people's lives help them get back to work spend time with friends and family relieve suffering particularly in situations and of life, but also in people with chronic pain,
And I have seen opioids destroy lives at a personal level. I come from a family background deep deep in addiction. I've lost close loved family members, too.
Addiction and I'm respectful of that. What I've learned is to not get into this binary mode of thinking it's either this or it's this but to treat opioids as a clinician
as a tool to be used in certain circumstances in some people not typically as a Frontline or first line agent typically much later down if they have failed other therapies, you cannot approach the challenge of opioids without appreciating the Deep complexity that we're faced with particularly now in society with all of the litigation on going and all the
The money involved it's it's a highly nuanced topic. So what what what more would you like to talk about
opioids? Well, I think that most people hear about the opioid crisis and just assume that they are quote unquote overprescribed that people are given opioid drugs as a Frontline treatment, perhaps more than they should that the addictive component which I understand is very real there the potential for addiction.
very real as well as the potential for
cross interactions with other things like alcohol and perhaps even other illicit drugs street drugs, perhaps if like if people can't fill their prescriptions and tolerance to the opioids creating issues where people then need more of them they're doing I have a not close family member but you know distant family member who had his entire life in arranged beautifully is a practicing lawyer with a beautiful wife and family.
Had a back injury was prescribed Oxycontin it it helped him initially, but then it set off some behavioral psychological Pathways that had him seeking more forging prescriptions when you know, he understood the law. He was a lawyer a he eventually went to jail got out the same thing happened again. He eventually ended up dead, right? So and I think there are many examples of that that we hear about in those are very Salient and very disturbing very saddening.
So I think that most people including myself here the opioid crisis and assume that what we really should be doing is Seeking a better alternative. But what I'm hearing from you is that there are use cases where opioids make a great deal of sense and that they've really helped improve people's lives and that none of what I just described or anything like it is experienced by those people. In fact quite the opposite. Do I have that right
perfectly and and that's again where?
We need to treat these at an individual level on a case-by-case basis and it one size doesn't fit all yes opioids were over prescribed.
I think everybody agrees to that in this country and we went through a period of time with massive overprescribing and there's a lot of nuance and reasons why and large part Physicians we get terrible education around pain, and we don't know how to treat it in general coming out of medical school. We got about seven hours of education on pain veterinarians get 40, it's great if you're taking I think your dog's name is
Hello. Yeah, unfortunately he passed but he took some pain meds for a short while but I found an alternative treatment that worked far better perfect, which turned out to be by the way low-dose testosterone. He was castrated like he was fixed on younger and I it's interesting I've gone I've said publicly on very large-scale podcasts that I gave my dog low-dose testosterone later in life and ameliorated a lot of his aches and pains at least from what I understood because he started moving better and feeling better and sleeping better and I expected the veterinary Community come after me with pitchforks.
Not one. Wow, did that and yet I heard from hundreds of veterinarians that said, yes, we wish that we could prescribe those sorts of things to people who castrate their male dogs later in life to ameliorate their symptoms. So that opened up to me a whole world of understanding about some of the restrictions that vet that vets face in terms of what they prescribed. There's a whole discussion to be had about that will do a series on animal and health that Health great. Well, that's hopefully our healthy to you get the point. Yeah, but when it comes to the opioid crisis in this
Russian yo, I think it's become so Laden with the idea that like doctors are on the take like they're getting paid to give opioids to patients and that's why they're doing that and I don't believe that necessarily be the case. But I think that's what the public perception is that it's all Financial.
Here's the here's the thing were there bad Doc's doing bad things. Yes. I'm going to invoke a good friend of mine Keith
Humphries at Stowe. Yeah. So terrific
terrific
Eric psychologist who has an addiction medicine psychologist and public policy person and the way he breaks it down and I have subscribed to this is you know, there's three types of Physicians. Remember there's about a million physicians in this country about a million.
You've got Physicians doing the right thing for the right reasons vast majority of docks.
We need to leave them alone. We need to support them. We need to help them do their job and not put more obstructions in their way. There is a much smaller group of Doc's doing the wrong thing for the right reasons what I mean by that is these are Doc's who did over prescribed opioids in this case in this context. They did buy into the marketing messages that were put forward.
They did not have much education around Alternatives in treating pain and they thought by handing out pills just pills in their very brief visits with patients. Remember Primary Care docs is my heart goes out to them. You know, what are they get 14 minutes or so the patient they gave them something that they thought would help they were doing the wrong thing for the right reasons,
but they believed that they were helping they didn't believe they weren't get catching.
Anshel incentives or okay, that's
right. Those people we need to educate them. We need to train them on proper pain management opioid prescribing D prescribing and then you've got the tiny little group at the top of this if you will pyramid. These are Doc's doing the wrong thing for the wrong reasons. These are bad docks. These are your pill Mills.
These are people breaking the law. They need to go to jail. And of the thing is is that that little group at the top in the million or so Physicians we have in this country. It represents such a small representation, but it got blown out by the media and everybody else particularly those Doc's doing the right thing for the right reasons got caught up in it and engendered a huge amount of fear huge amount of fear on the physician side.
And then what happened is the docks just started abandoning patients. They cut their patients off. I had a young housewife two young kids doc Cut Her Off from a little bit of Vicodin that she was taken intermittently for some back pain that had been well managed on this she was doing all the right things cut her off. She turned to black tar heroin, you know, California great state of, California.
The for Nia tried an experiment where they monitor death certificates in our state for and the docks prescribing opioids for that and they went after the docks thinking that if they targeted the docks doing that it would lead to a reduce a reduction and opioid deaths it led to a doubling I know counterintuitive because what happened is the docks abandoned the patients.
And so we have to be aware of the negative consequences of this now the current not trying to minimize the opioid crisis because it's real but we also now need to put some contacts. The opioid crisis is being driven.
by the illicit Fentanyl
It is more if you just look at the CDC data, it's very clear. That fentanyl is coming in Via Mexico China and others is what driving most of the deaths.
Keith getting back to Keith lead a beautiful Lancet Stanford Commission on the North American opioid crisis and put together a very rational plan. I just finished serving as a senior advisor to the medical board of California where we revised our prescribing guidelines here.
They were very Draconian before hard limits.
Made people fearful both patients and docks and we've shifted it back over to put the control back in the hands of the physician-patient relationship. We're hoping it'll make a difference.
You can see I'm I'm going on a bit here. There's there's just huge complexity in this space. I understand you're going to do an episode, you know, some some time on it in the future and I
hope
the audience has more opportunity to listen to this other questions. I can answer for you though
on that. We really appreciate the thoroughness of your answer. I think that you set a picture and a context that I certainly didn't understand or appreciate and it
Like one certainly not the only but one of the major issues is the creation and the propagation of a black market by doctors cutting off patients presumably out of fear those patients then seeking not any but illicit or black market routes to treating their pain which you can understand why they would do that. I mean, I'm not justifying anyone doing anything illegal, but somebody's in pain and they had something that worked and now they don't
and they're going to go looking for things that are similar to that theme and you're telling us that fentanyl in street drugs basically is what's killing people presumably I doubt it's fentanyl prescribed by physicians or perhaps it
is it's not know there used to be a bit of confusion around that because fentanyl is a prescribed medication in a patch form and in at Roche the troche use for end-of-life cancer pain, but unfortunately some of the
Coding used by the CDC and other words got that confused with the illicit and so it took a while to get a better handle on it. But I think you know we do now yes, most of it is being driven by the Fentanyl 's and we're just seeing this incredible epidemic wave of it. It can be made so cheaply brought across the borders reasonably easily.
Something we definitely need to do to address. We want to be careful about not conflating that crisis with the issue of pain, which is an epidemic in its own. Right and for the segment of people who are using opioids responsibly and effectively for their pain.
And that's where again that Nuance comes in. Our their patients who are also on opioids that have been weaned down you can wean them down gently compassionately and they do better the answer is yes. My partner Beth is just finishing up a study on that and you know showing that with Compassionate Care a number of these patients can be weaned down who voluntarily want to come
And sometimes I find their pain actually improves and part of that Improvement. Maybe that opioids have degrees a side effects.
And by elimination of those side effects and the the other aspects, they're seeing
Improvement. Could you list off some of the more commonly used opioids,
you know morphine and its commercial louvers commercial deliberative CMS content, which is a long-lasting version of morphine oxycodone, which by itself is a short-acting medication but when you encapsulated in a long-acting version, it becomes Oxycontin, which was the trade
In the Purdue put forward fentanyl. We mentioned comes in a patch form. There are mixed agents like Tramadol, which is a kind of a week opioid but also has what's called serotonin and norepinephrine reuptake inhibition. We've got Dilaudid which is a version of trading for hydromorphone. So there's a slew there's I don't know.
More than 20 different opioids within that list of 200 medications that we have.
Methadone is another one people usually think of methadone is a medication used to treat addiction people go to methadone clinics. It's a long-lasting opioid in the right person and certain circumstances. It can be used effectively for chronic pain.
By and large they all have the same or similar mechanisms of actions working on opioid receptors. This is getting back to your original question to me about where these things work.
There are opioid receptors in the periphery. There are rich sources of opioid receptors in the spinal cord and the dorsal the back part of the spinal cord. And then there are many areas in the brain that are rich in opioid receptors. It's you know, it's all a naturally occurring area when we put in an opioid by mouth. We are binding to those receptors and activate.
Eating those neural circuits in many cases when I say activating they have an inhibitory role. I mean, that's one of the major
parts.
Is there any role for benzodiazepines in pain
relief?
Rarely, if too many of my colleagues would say, you know Sean it's just a hard no.
And Rod have to come up with an edge condition of somebody who has a generalized anxiety disorder under poorly treated with anti-anxiety lytx with chronic pain and they wouldn't you find you treat their anxiety would like a benzo it helps with their pain as well. But these are Edge conditioner by and large know
what about Kratom. I had a odd experience with kratom.
And I've never taken it. The experience was the following. I started learning about it hearing about it from listeners on the podcast realized by doing a little bit of a web search that it's available over the counter and that certain people like to take it often like everyday at low doses or even higher Doses and that there was huge variation in terms of the amount of Kratom in the various products and how much people were taking some people talking about Kratom as something that was as if it were
And we can ask whether or not indeed. It is innocuous. And so I put out a tweet I guess now that Twitter is called X, I guess I put out an X anyway doesn't matter and I and I said that my first pass view of the literature on Kratom. The scientific literature is that you know, it had a lot of properties similar to opioids although different as well and that it seemed kind of odd and maybe even problematic that it was so widely available and I got bombarded.
With I don't want to call them Kratom enthusiastic because what I soon discovered was that these people were angry with me for placing even a partial Shadow and Kratom, but what was interesting to me was that they were saying that in their case and I'm assuming they were telling the truth that Kratom had helped them get off prescription opioids and that they heavily rely on kratom in various levels of dosage in ways that they felt really help them. And so
Two things happen one. I've been put in the crosshairs of the pro Kratom Community not to its severe extent but perhaps the more important thing is and I want to thank that community in part for you know, now it's inspired me to do a deep dive search on Kratom. I'm going to be interviewing one of the Laboratories that's done a lot of the research on Kratom later in 2024. But also it's made me realize like they're these compounds that are available over the counter that many people feel so passionately about
Because they really feel like it's helped them. I'm not saying it has I'm not saying it hasn't but then again I've never taken it. What is Kratom at or perhaps what receptors does it tickle? And what are your thoughts about Kratom and people using Kratom and maybe I'm pronouncing it wrong. I've also heard Kratom created a I'm calling it Kratom.
Yeah Kratom is this natural substance that does have as you said Opia Dyrdek properties as well as others. That is not fully.
Stood it's been available. Well, naturally for many many years brought in to the United States and I've heard the same stories and I just want you to be prepared that anything I say about Kratom. There's going to be some angry people after this and it is what it is. I have heard the same stories that you have heard about people taking Kratom and saying it's helping them to stay off of prescription opioids or illicit opioids and I get that I think in some way
Binding opioid receptors and reducing the natural craving for these other substances and it makes perfect sense methadone. Does that buprenorphine which I didn't mention before but is a is an interesting opioid that binds to these receptors and it reduces craving.
Where I have challenges is in just because something is natural doesn't mean that it is safe. We are seeing an increased number of Overdose deaths deaths associated with Kratom. Is it polysubstance Yen some cases it is but I think there's a lot we don't know. So so
polysubstance people taking create them, but also
qahal benzos.
back to the benzos
Personally, I think we need to put a lot of research into this agent. And if it merits that I think it should be a prescribed substance. I think part of the challenge that we have is that we don't understand the quality the purity of the dose that people are taking of this thing similar type of story with cannabis by the way, so
I'm hoping that we're going to get the research that we need to really understand what it's doing and whether it is safe and effective. I'm left with a lot of unknowns right now.
You mentioned cannabis is cannabis effective and by extension is CB D effective for managing
pain. Yeah, there's another controversial one. You'll get a few comments about whatever I say,
you know in general listeners of this podcast. Yes, they tell us where they're upset that.
Also tell us where they agree our goal here is never to satisfy everybody. But just to you know, some of this lands in the realm of Highly Educated opinion, some of it is still as you point out speculation because we don't really know what Kratom sources people are taking or cannabis and Etc, but I think you'll find and my experience has been that people appreciate that we're having the conversation and we do read all the comments and those comments often as I mentioned in my earlier anecdote.
About that tweet often direct us to explore things further and we can always have a you know, a second discussion about this down the line. So we invite all your comments and
criticism cannabis. Well,
Here's what we know in carefully controlled laboratory situations cannabis has been shown to reduce neuropathic pain. That's that nerve related pain from people who have either nerve injury diabetic neuropathy postherpetic neuralgia terrible burning nerve pain condition. It has been shown to reduce that.
in small samples
from larger-scale epidemiology studies and even larger like Clinic based studies that I've done we find it has not been particularly helpful on average compared to people not on cannabis.
There's a lot we don't know about the causality of that and the direction of it.
but all to say that there are many many questions that remain I think the challenge that I personally have is that we're running huge population level experiments as we speak right now by you know, providing unfettered use of cannabis and the bad news is that we're probably going to see some real untoward consequences of it and we're already are the good news is I'm hoping that at a
Level will be able to use that data to really inform what's going on with cannabis. I mean some of the challenges are what I referred to with create them cannabis is not cannabis is not cannabis Edibles thce to CBD ratios that dose. Yes, all of that. We don't know what you're getting. It remains a schedule 1 drug by the DEA. I in some of my leadership roles and others have called for scheduling of it as
A schedule to why why not to purposely try to restrict use but by making it a schedule 2 drug you've now made it so much easier to research.
I don't know if people understand how many barriers there are two scientists studying schedule one drugs.
Could you explain schedule 1 versus schedule to
thank you. Yeah, so schedule is the scheduling of drugs is a categorization that describes their abuse liability. And so you have drugs like PCP heroin cannabis, which are schedule one which are defined as having high addiction.
Cantrell and no utility which has
almost wild because when I think about PCP phencyclidine, I certainly don't want people to run out and start taking PCP but chemically and physiologically PCP is ever so similar to ketamine.
And you know, the rarely is as discussed by ketamine is now widely used as a therapeutic presumably ketamine isn't scheduled to maybe even schedule 3. Yes, and so some of the the stuff that's thrown into schedule one makes no sense.
Its historical its all his it's decades and decades ago of history, and clearly cannabis should not be a schedule one hands down no question. Bye.
Drilling it though. You will have the societal benefit of being able to make it more easy to study and then you get the NIH and the FDA into this and we can start really getting answers to the questions. Which do I think it works at the end of the day do I think there is some variation of cannabis THC CBD ratios that will provide some benefit. Oh, absolutely. There's too many receptors in our brain that
Are involved with modulation of pain. I just don't know what those are friend of mine Mark Wallace runs pain at UC. San Diego has come up with a really nice recipe cocktail of ratios of THC to CBD that he feels very strongly that he can help people using that as an active agent.
Yeah. I know that in Colorado. There's a strain of cannabis where they it's pure CBD no th
He think they call it Charlotte's Web and parents of children with intractable epilepsy will actually move to the state of Colorado in order to get it because it seems to be effective for the treatment of certain forms of pediatric epilepsy that was shared with me with one of our colleagues Nolan Williams when he was a guest on the podcast. So these plant based compounds have have their place whether or not it's Kratom perhaps right? We're remaining open about that or cannabis the THC or the CBD or some combination think it's
We interesting I think as long as we're talking about plant compounds. How do you view the fields that are what I would call somewhat adjacent to traditional medicine. So things like acupuncture Chiropractic physical therapy and so forth
as a pain physician within the field of pain medicine or pain management, I think about six broad categories of therapies that we provide for people with chronic pain. One of these is the medications and there's a whole lot.
Group of categories of medications 200 or so available to nerve blocks and procedures these range everything from trigger point injections to nerve blocks with local anesthetic and steroid on up to minimally invasive procedures, like spinal cord stimulators implantation of drug delivery pumps three psychological and behavioral therapies pain psychology, which has many forms now can be very effective.
If for physical and occupational therapy approaches to chronic pain 5 this is what we typically call complementary alternative medicine approaches. It's a little bit of an outdated term but I think of that is acupuncture nutraceuticals. These are the over the counter agents that have actually shown to have benefit in pain that you can get over the counter and last but not least six what I call Self empowerment or increasing your agency and here.
It's about education. It's about learning skills. It's about being here on the huberman, you know Lab podcast learning about pain. It's at self-empowerment. And what we find is that those six categories all brought together typically have the best benefit for people living with chronic
pain to a lot of people listening to us right now then go yeah acupuncture. I mean, this is a thousands or tens of thousands of years will practice that
Clearly is grounded in a lot of clinical data and clearly works and then other people will go. Oh my goodness. They're trying my acupuncture like sticking needles in the body or they're just like pain treats pain. Is that what it is about but as you and I both know unless it's being performed incorrectly acupuncture is not painful to receive does acupuncture help treat certain forms of pain. Is there any scientific basis?
Yes. Yes, there is do I understand.
What's going on with acupuncture having completed an actual and then I uh funded acupuncture
study. I just saw that
published. No, you know, I'm just being straight. We still don't know exactly how acupuncture is working. We do know that there's a nice study that showed activation of peripheral adenosine receptors that have a peripheral analgesic effect. We know that acupuncture and as compared to Sham acupuncture engages different.
Brain regions. It's interesting that many of the a cue points over lie peripheral nerves and so by needling those nerves are we causing a central change? We're turning down the amplifier. If you will in the brain may be where does this fit into my clinical use? My usual statement is that if you can afford the wallet biopsy give it a try.
Although find a really good acupuncturist. I've oh, yeah. Yeah, I've had acupuncture done. I wouldn't say many times but several times and I will say this one of the acupuncturists I went to put needles in my face and I ended up having to go to Stanford Derm to get some of the angiomas that were like blood vessel growth. That was the consequence of those needle insertions. And so I to the point where I won't if I go to acupuncture my don't put anything don't put any needles in my face because I'll take an angioma on my leg or whatever I do.
Our and I it's not vanity, but I didn't like the way that the needles were introducing angiomas to my face. Now that was probably because this acupuncturist wasn't doing things correctly not saying all acupuncturist do that. But here's the problem. How do you know which acupuncturists are reliable versus not and for that matter, how do you know which physician is reliable versus not. I mean, I work at an institution like Stanford where I can ask a lot of people and I still might senior administrators won't like this. But when I get a recommendation from a dock at Stanford, I
I always call somebody at UCSF and cross-check. Yeah, and I don't tell them that I'm cross-checking and I'll do the reverse as well. When I when I was at UC San Diego, I would check up with at Stanford. So but most people don't have access to that kind of community. I mean, I can pick up the phone and contact somebody in pretty much any medical specialty and at multiple institutions, but for most people there waiting into the abyss of acupuncturists of Physicians. I mean, how are people supposed to navigate this
you found?
Perfect way to do it and many of us do the same thing. And for those who don't have access to high quality experts you can use variations of that. So you're right with acupuncture most of the ones I've been associated with we use in the clinic or outside or all have been high-quality. The recommendation would be to try to get a referral or recommendation from somebody who refers to that acupuncturist. Doc's want to have relationships with people with
other clinicians that do a really good job. We don't want to be referring to somebody who's bad because it reflects badly on us. So it's really doing what in a way what you were doing. So try to connect with your primary care doctor others and get some recommendation for who is high quality.
With regard to clinicians pain Physicians for instance that stuff there's five to ten thousand of us that are sub specialty trained out there. If your pain is really complicated a complex pain problem. You're probably better off with a tertiary referral center that can provide comprehensive Services where
possible so, is there a is there a centralized website where people can say okay, I live in the state of Iowa or I'm
You know a lot of our listeners are overseas or you know, where people can find out the like the the ratings based on patient experience. Although that can be complicated. I confess sure the one star out of five star ratings are a little bit more Salient there been studies on this people tend to if you know, you see a negative review those tend to grab your attention, even if they're fewer of them than the many thousands of positive reviews, but I mean patients should be able to get the information that they want about previous patients experience,
right? Yeah. I got a
You're the patient ratings. It's a highly manipulated situation. Also. Well, you can pay companies to help jack up your ratings. I see that's it's rather easy. I see it in the community all deflation of real my yes inflation of ratings. And so then you inflate it in an overcomes any of the negative ones. We haven't taken an approach on this and maybe that's naive of us.
You know, we see 25,000 patient visits a year and only a tiny percentage of them put some rating and it's probably the extremes undoubtedly, but we don't manage it. I know that in many Community settings that they do. I didn't answer your question. Is there a reliable source of quality? I still think at the end it's going to be relationships and word-of-mouth and referral I do the same thing you do. I you know to see Hannah Watford the allergist.
Ask my primary care Doc. It's a who's the best who is the person that knows the most about food related issues?
Well some really entrepreneurial guy or gal or group of guys or gals will put together a website or an app or something that really addresses this problem head-on. Well, that is I can think of very few things more useful than a truly independent way of understanding prior patient experience and finding the best person for a particular problem and I think a i
Can help with us. Yeah, but I think Ai and you know human interface anyway somebody out there should do it. I'm curious about Chiropractic for a lot of people gain car not chiropractors. Let's not talk about the people specifically but Chiropractic a lot of people put acupuncture and Chiropractic adjacent to one another but my understanding is that insurance often will cover acupuncture but not Chiropractic work. Maybe I got that back.
Words, maybe I'm just all out wrong. But you know with Chiropractic work you're talking about often the attempt to relieve compression of nerves certainly nerves are being manipulated. If any part of the body is being manipulated, I guess manipulate its kind of a word that implies something sinister is happening is being adjusted. What are your thoughts about chiropractors? Assuming the chiropractor is well trained and responsible. Can it help pain? Can it help back pain neck pain whole body pain.
Yeah.
Yeah, first of all acupuncturists and Chiropractic or two entirely different professions just to just to be clear for people and they sometimes get lumped into a similar category of pain treatments and that may be where you know that comes from just closing out on the acupuncture again, just to summarize. Yes in some patients in some circumstances. I found acupuncture to be useful and it's worth a try CMS center for Medicare.
Is now paying for acupuncture for people over the age of 65 Medicare for Medicare patients. That's something recent and we were happy to see that I believe that was for back pain. That should be fact-checked but Chiropractic.
Mixed data well-controlled studies some of shut some have shown that it can be helpful for low back pain some have shown. It isn't it's truly not clear the type of Chiropractic that involves the doesn't involve kind of, you know, the the fast High Velocity manipulation is a physician. I have some concerns about that particularly around the neck. I've taken care of patients that
Had vertebral Artery Dissection, 's from that rapid
wrenching. What is a vertebral Artery Dissection?
One of the the the main arteries that goes from the body to the brain and the back portion of it is called the vertebral artery. And when you do these high velocity manipulations, there is a risk albeit small of having a dissection or an embolus thrown off and I've had so it's like a stroke. It's like it is a
it's like a stroke but there's a lot of approaches that can be done that in some patients have shown some shown some benefit. I think the key with a number of these therapies, and I don't want to single out acupuncture acupuncture or Chiropractic.
If you go to them ask yourself, am I getting durable benefit meaning everybody feels good after a massage, right? But couple few hours later. It's kind of worn off. It's a nice experience in the moment. For most people if you're finding that for acupuncture Chiropractic or anything for that matter, you know, ask yourself. Is it really?
Providing you durable benefit that is worth the effort or is it just rapid? It feels good in the moment.
We tend to use that in our clinical practice has a threshold, you know, and we like to see things that last for a longer period of time and in many of these treatments whether it be acupuncture Chiropractic we use those as an inroad into more of a functional rehabilitative approach.
Meaning when you get chronic pain you tend to withdraw you tend to stop exercising you stop moving your muscles atrophy. You become deconditioned because of the pain and so we want to use these tools that we've been talking about is a way to get people engaged in activity to correct the underlying biomechanical issues that may be present. And so they all need to be appropriately staged and that's where working.
The good clinician can help with that.
Yes, certainly my case anytime I've had back pain, even when it was very severe provided. I wasn't harmed and I was just hurt continuing to move and not becoming sedentary was absolutely the fastest route to recovery and and in particular doing certain exercises that that were particular to my case. What if any is the role for physical therapists in the treatment of chronic pain?
Absolutely crucial absolutely crucial despite being a physician not a physical therapist. I have great appreciation and respect for what the physical rehabilitative approaches do because at the end of the day, we're trying to get people back to an improved quality of life and physical functioning. I mean that and is often what people are most looking for control over their pain control over their life. Yes reduction in pain, but more being able to do more things.
They're tying in with good physical therapists occupational therapists people who can do goal-setting absolutely critical all of the treatments that I provide typically are meant to help support an increase in physical rehabilitative approaches. And so when I do nerve blocks or procedures or give a medication and if we end up reducing some pain we want to tie that in with
or activity
And what the physical therapists are great, particularly those trained and chronic pain is knowing that difference between hurt and harm they can
work with people to
know what safe for them to do to rehabilitate. They can teach them more about body mechanics and help improve endurance and strength. They can work around pacing pacing is so critical for people with chronic pain. Now, this isn't just exclusive to the
Physical therapist the psychologist do pacing. I do pacing what is pacing?
Here's the problem with chronic pain one of the many problems it waxes and wanes. And so what happens is you go out and have a good day. You go out like gangbusters and you go do everything that you haven't been able to do for the last week because you've been in pain.
And then you pay the price.
And when you pay the price your back in bed or you're on the couch and you're not moving and what happens is you go into this rollercoaster of activity and no activity at all. And what happens is it in trains in our brain and it's a classic negative reinforcement model. This is classic psychology. And so then people become fearful of more movement.
And as a consequence, they get more and more disuse atrophy and then more disability. So the key, what do you do about that?
The key is you set small goals baby steps.
If you can walk comfortably for a block right now.
Great walk that block tomorrow, maybe walk a block plus an extra 50 feet and maybe the next day another 50 feet no more no more if you're having a great day, don't go do five blocks.
You're training for a marathon you're training for the long win. Now, what's going to happen along the way is it you're going to have good days and you're going to have bad days on the good days. Don't go out and exceed it set a threshold time at on your watch set a Distance on the bad days. Recognize. We all have bad days. Everybody has bad days.
And you know, you may need some rest during those bad days. But then the next day get up and restart, you know, where you were.
And that's the type of thing a physical therapist good pain psychologist good physician can help you with and tying that in by the way with these other therapies,
very interesting. I've never heard of pacing but it makes total sense and I can see how people would really hinder their own progress without that basic understanding which thanks to you we now have and it's something that hopefully all these therapeutic modalities. Keep in mind. I mean, I don't know.
Not the acupuncturists are talking to the physical therapist or talking to the physician. But I guess this is the reason for referrals right why somebody has a primary care doc then and it radiates down to the rest. Is that why and an
ideal utopian world? That's exactly it. I mean outside of Comprehensive Pain centers that have all of the stuff co-located you are dependent on a dock to play quarterback and bring all those referrals.
Together it's incredibly challenging for a primary care doc to do that with a limited amount of time. They are given to see a person this is where we're trying to use technology to help better with that integration. And I do think there's hope for the future will have better ways of managing that and handle it.
What is your view on non-prescription compound so-called supplements or nutraceuticals for the treatment of
pain fascinating topic.
This country is rather unique and having you know, a wide slew of over the counter agents that are actually prescription in Europe and in other countries and there are over the counter agents that have been shown to be effective for a number of pain conditions.
So for neuropathic pain acetyl-l-carnitine is one of them acetyl-l-carnitine is thought to work on mitochondrial metabolism and improved mitochondrial health and it's been used I believe is a anti-aging and maybe even a cognitive enhancement agent you need and it's been studied out of an Australian study. I think it was called the Sydney trials actually and what they found it's one of the few over the counter agents.
Did actually had disease-modifying properties meaning they studied this in diabetic neuropathy.
The clinical endpoint was not pain reduction. The clinical endpoint was nerve conduction velocity changes and that's how we monitor nerve health is a normal nerve. They move nerble pulses move at a certain rate and when they're injured from diabetes, they you know, it's much slower and you lose signal this actually improving your health. You can buy those at a vitamin shop order them online alpha lipoic acid is another one out.
Lipoic acid at least two mechanisms one is it's a free radical scavenger and second that's been more recent is it is a T-Type calcium channel modulator and calcium channels are in our nerves and it turns those down and it can have some benefit for neuropathic pain people have taken alpha lipoic acid for a general sense of well-being.
And it is generally well tolerated it can cause a little bit of stomach upset. I will tell you I took this one myself for a while. And this is you know, again, just an N of 1 what I found though is you have T-Type calcium channels in your heart and I do hit a high intensity interval training and I was Finding I couldn't get my heart rate over 150. So I had I stopped it that's not an adverse event. That's just an annoyance, but that's useful.
Vitamin C. So if you're going in for surgery and it's a maybe a nerve related surgery that you're going to have they found vitamin C prophylactically can reduce the likelihood of having certain nerve pain conditions after surgery fish oil of the Omega-3s have been found to be a beneficial around chronic pain more recently. The data here is on smaller numbers creatine, which I imagine you've probably
talked about it at some length, but creatine has shown in small pilot studies and benefit and fibromyalgia and some other types of conditions. So there are a number of these substances that are backed up beyond the you know, the anak data that we joke about the anecdotal. There's actually good randomized control trials and this is something that people can easily take advantage of just be
Mindful that just because it's natural just because it's over the counter doesn't equate with 100% safety meaning get educated about the side effects in the Adverse Events get educated about the drug drug interactions the agent agent interactions. And for instance. There are these over-the-counter agent some of which you want to be careful of.
And not taking when you're going into surgery because they can be a platelet Inhibitors and they can cause you to bleed more
isn't vitamin C one such comp substance
that causes excessive
bleeding or some people report that high levels of Omega-3s can increase the can reduce the viscosity of the blood meaning you bleed easier
the Omega-3s a fish oils. Yes. Absolutely the vitamin C. I'm not familiar.
You're honestly with as a
blood thing agent. Maybe I'm misinformed there
or maybe I'm just forgetting it, but that's that's when I don't usually think of is a blood thinner.
Someone will put in the show note comments one way or the
other it corrected I but there's a number of these over-the-counter agents that are that are available. The vast majority are innocuous that I've mentioned that I've mentioned. There are two us
meaning they don't cause harm at the at reasonable dosage thing.
But they can't have positive
effects. Well a perfectly stated. Yeah.
Well, thank you for sharing that list. I think as you mentioned many compounds that are only available by prescription overseas are indeed available over the counter in the US and this area of nutraceuticals like supplements is still an area that's actively debated depending on people stance, but it's refreshing to hear somebody who's you know, I formally trained physician and and scientists who
Is so many different approaches in the treatment of pain along those lines perhaps you'd be willing to talk about the psychological treatments that can be effective for
pain again absolutely critical in the management of people with, you know, wide range of pain problems and recall what we talked about is, you know, this is nociception. These are the signals coming up to the brain once it hits the brain, you know, we're dealing with everything.
That person is lived through and also is currently experiencing meaning their levels of anxiety depression how they cope with pain in the past how they cope with it. Now early life experiences is a paper that just came out in Jama literally in the last few days where they did a meta-analysis of brain Imaging studies on people with early adverse life events and what they found is abnormality.
Is an emotional processing emotional functioning and people who have these giving strong evidence that what happens to you early in life impacts us as adults and stays with us it changes our wiring now.
This is where in part pain psychologist behavioral therapist can come in. They can help with some of the maladaptive coping the thought processes involved with pain. They can help teach skills. So for the vast majority of pain psychology, this is not your typical psychoanalytic lying on a couch, you know talking about you know, whatever. This is about teaching people skills.
Incredibly helpful. Does it eliminate pain few of the things that we do actually eliminate pain? What we're trying to do is Chip Away, you know a little bit with this medication a little bit with this procedure. Sometimes this procedure that with psychology. We're trying to hit all of these Pathways in aggregate to make a real difference.
The pain psychologist use classically techniques like cognitive behavioral therapy which involves often recognizing these unhelpful thoughts and patterns that we all get into around pain and even life to interrupting those thoughts to helping people again with goal setting and pacing to teach people relaxation techniques through deep breathing.
Like biofeedback and Silicon Valley where I practice the engineers love the biofeedback. I'm an engineer by formal trainings. I get it but it's that closed loop feedback because remember the brain is controlling the periphery and controlling the sympathetic nervous system. And when we're in pain our sympathetic nervous system gets wrapped up when the sympathetic nervous system gets revved up blood vessels constrict heart rate goes up on
Muscles get tense, and we need sometimes ways of learning how to calm down that sympathetic nervous system cognitive behavioral therapy mindfulness based stress reduction acceptance and commitment therapy or some of the tools that they use. My partner Beth has developed a brief intervention called empowered relief. Yes. I'm biased it works. We've studied this in an nih-funded study and it's
I have getting eight weeks of cognitive behavioral therapy and two hours. Wow, not meant to replace CBT but as an additional tool and you're going to see as time goes by more and more of these tools come out and the beauty of them is they're going to be much easier to disseminate broadly to the public then for instance a pill and I can't we can't just go put into FedEx or the US Post Office, you know start sending out pills, too.
Everybody but we can develop treatments online that can teach people skills and really help
is that the plan for this abbreviated but equally effective cognitive behavioral
therapy. Yes. Now you're getting into kind of my baths and my life mission. So, you know, I've spent the last 12 years D building a digital platform a health platform that we've integrated into clinics and
High quality data covering all aspects of people's physical psychological and social functioning. And the reason for that is to address a critical need that we have on better quality data about people the data and the information that we have on people with pain and many health conditions is terrible.
And so I created this platform to be able to capture high-quality data put it to use use AI in the background for prediction and now
Beth has created these brief interventions, which we are integrating and the notion is to make that widely available for free. We're giving it all away. And I said this is a life mission. We both have been blessed to be at Stanford where we have everything.
But you know you go just 30 miles 40 miles outside of the Bay Area and you're in a healthcare desert and I don't say that disparaging to any Doc's working out there but it's different. There's only a handful of large academic centers and large practices in the country. When you get outside those in those catchment areas people struggle with how to get good quality care. You asked that question earlier. How do you find good quality?
Leti care
And so we're working to make that that available to
everybody fantastic. I was going to ask you as a final question. What is your if you had one wish for the future of pain medicine and the treatment of pain what that would be before you answer that. I'll just add an answer that you already gave which is it sounds like the implementation of this incredible set of tools and database that you've collaborated.
With dr. Darnell Beth Darnell to to develop as at least one of them. So now that that that answer was given by me then you can it frees up the opportunity for you to give another answer. What is the if you had one wish for the field of pain medicine going forward, what would that wish me? Yeah,
so a few years ago. I co-led for the country the development of the national pain strategy.
And this was sponsored by the NIH and health and human services and I co-led this with dr. Linda Porter from the NIH we brought together a t National experts and pain research pain clinical care pain policy and people with lived experience with pain. We put together a strategic plan for the country on how to enact a cultural transformation and change the way we assess care for people with pain how we educate professionals.
How we communicate with the public?
My wish would be for full implementation of the national pain strategy it unfortunately took a backseat when it was released the same time with the CDC opioid guidelines and the opioid guidelines sucked all the oxygen out of the room, but the the Strategic plan.
It was well thought out it's the one that we have for our country. It's non-controversial nonpartisan. It is motherhood and apple pie and it's if we just actually Implement what we put forward. It'll make a huge difference in the lives of people living with
pain. Is there anything that people listening to this podcast can do to try and move the implementation of that initiative APA. Are there Congress people to call?
I mean, that's how that's how I learned in junior high school and high school what little I attended and by the way go to school folks I had to catch up a lot. But I do remember them saying that you know, this was a democracy is a democracy and that those phone calls and letters can often matter for what gets you know sent up the flagpole and what ultimately gets approved and
implemented beautifully stated. You're absolutely right. And in fact, the night is for the national pain strategy originally came about
About through a number of concerned citizens with pain doing that very thing and lobbying. What became a bipartisan you don't hear that much anymore bipartisan effort to put forward National Pain Care Act that got put into the Affordable Care Act that called for the development of an Institute of medicine report on pain that led to the National pain strategy all starting with
Concern people making those phone calls and writing those letters. So that means
calling your congressmen and congresswoman leaving messages. I hear this works. I mean, I know people they're doing this for other initiatives and one call to calls doesn't make much of a difference but that if people are saying, you know, this is important to them that people didn't power eventually start taking action
the legislators they listened and and in part again part of this life mission both developed.
This platform. I've created a nonprofit called pain USA and its main mission is to help Advance the implementation of the national pain strategy and baked within that is this platform also to use high-quality data to better inform the care of patients of people with pain and to deliver high-quality treatments because we do know also that people listen to data and we need good quality data to influence.
Messages but please yes, make those calls write those letters. It does
work. Well Sean. Dr. Mackie. Thank you so much for everything that you're doing. You took us on quite a tour in terms of depth and breadth of the thing that we think of and it unfortunately in some cases experience as pain, although we also learned it's highly adaptive in some cases can protect us does indeed protect us.
Thank you for taking us on that tour of the biology the psychology the various treatments the context in which all of this exists. We touched into some somewhat controversial areas, but I really appreciate the thoroughness and the nuance and the sensitivity with which you touch into all of those issues and just on behalf of myself and everybody listening. I just really want to thank you you've contributed a great deal today to the public education of what pain is what it isn't and how to treat it. So, thank you.
So
much. Thank you. Dr. Huberman. I appreciate the opportunity to come on and spend some time and you're giving a platform to help educate and inform people out there. I got to tell you Nobody Does it Better you've been absolutely amazing and thank you. Again.
Thank you. It's a labor of love and I appreciate the kind words come back again. Thank you. Thank you for joining me today for my discussion all about pain and ways to control pain with dr. Sean Mackey. I hope you found the conversation to be as.
Resting and as informative as I did to learn more about and explore some of the resources that dr. Mackie mentioned during today's episode. Please refer to the show note captions. If you're learning from and are enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us in addition, please subscribe to the podcast on both Spotify and apple and on both Spotify and apple you can leave us up to a five star review, please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast.
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