Good Life Project - Top Pain Researcher | The 6 Keys to Relieving Pain

Episode Date: June 13, 2024

Stanford neuroscientist Sean Mackey, MD, PhD reveals pain is highly subjective, shaped by our beliefs and experiences - not just injury signals. He unpacks chronic pain's persistence, promising treatment strategies like brief behavioral therapies, and research toward personalizing care through biomarkers and digital platforms. An illuminating look at pain's complexities.You can find Sean at: Website | Instagram | Episode TranscriptIf you LOVED this episode you’ll also love the conversations we had with Dr. David Spiegel about the surprising science of hypnosis, pain & habit change.Check out our offerings & partners: Join My New Writing Project: Awake at the WheelVisit Our Sponsor Page For Great Resources & Discount Codes Hosted on Acast. See acast.com/privacy for more information.

One of the biggest problems that I see in society, in the United States and globally, are that people feel invalidated about their pain experience. They're dismissed. And unfortunately, that burden frequently falls on women because in many of these conditions, we don't have a clear source of nociception. We can't put our finger on the thing and say, this is what's causing it. This is why chronic pain is often referred to as the invisible disease. And so these women, but also men, are frequently dismissed by their loved ones, their families,

their friends, and unfortunately, the medical profession. We need to validate people's experiences first. Understand that what they're experiencing is real. So pain is something that so many people live with, sometimes for years without ever really understanding what's going on and how to effectively deal with it. There's so much misinformation and misunderstanding about everything from chronic pain to migraines and headaches and general aches and pains, even acute pain from injury or illness. What's really happening here? What is pain? And most importantly, how do we get out of it? Even if it's been there for years and you've been told there's no cure or way out of it. I wanted to

understand pain and the body on the deepest level and also learn about some cutting edge approaches to it, especially chronic pain that are truly changing lives. So I asked Sean Mackey, one of the country's leading authorities and researchers, to join me for an eye-opening and myth-busting and ultimately profoundly empowering conversation about pain and what we can really do about it. Sean is a renowned expert in pain medicine, serving as a professor and chief of the Division of Pain Medicine at Stanford University. And with a background in bioengineering and a PhD in electrical and computer engineering, as well as an MD, he has been just instrumental in advancing our understanding of pain through his research and

leadership in the field, including serving as the co-chair of the National Pain Strategy, which aims to transform pain care through an integrative national action plan. So in this conversation, he and I, we really delve into the subjective nature of pain, the distinction between what he calls nociception and the actual experience of pain, and this just multifaceted treatment approach that combines what he calls the six different pillars of pain treatment, medication, procedures, psychology, physical therapy, complementary approaches, and self-empowerment. We also discussed some really exciting work that's being done to create scalable digital platforms for delivering quality pain care and brief behavioral

interventions to underserved populations. So excited to share this conversation with you. I'm Jonathan Fields, and this is Good Life Project. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you 8 hours of charge in just 15 minutes.

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when we use the phrase or the word pain i realize realize this is broad and complex, and I'm sure we'll deconstruct it. But sort of like on a meta level, what are we actually talking about? into what it is and what it isn't. Pain, first of all, is our harm alarm. It is there to keep us out of danger, out of harm's way. It is one of the earliest experiences known. So it goes back all the way to single cell organisms, and it was basically either pain or reward. It was those two things that either drove us towards something, food, oxygen, shelter, sex, versus pain, which was to protect us from predators. And it's an incredibly conserved experience. It's evolved over untold millions of years. And as I mentioned, it is there to protect us from danger.

Now, in humans and in higher level organisms, it has a experiential aspect to it. What do I mean by that? One of the most misunderstood aspects of pain is that it is all linked to precisely something going on in the body. It is something that is occurring out in your hand, your arm, your back, and that what is going on out there is pain. And the thing is, that's not pain. We have another term for that. That term is nociception. And I'm sorry, it's a technical jargony term. I didn't create it. But it is meant to reflect electrical signals that are generated during harm or injury to the tissues. So when your tissues get injured, they generate an electrical signal.

That electrical signal, nociception, is sent up into your spinal cord in your back where there's a little bit of circuitry there, a lot of circuitry there that's processing those signals. It's still nociception, and that's sent up to your brain. That's where the real magic happens. Because that signal, you've got your big computer up there, is taking that input from your body. It's interpreting it. It's shaping it. And it then becomes your individual, unique experience of pain. And that's one of the key messages here is that pain is a highly subjective experience. And you can think of it as many of the other experiences out there. You had Judd Brewer on your show talking about anxiety. That is, anxiety is an experience. Depression, happiness, love, all experiences. The thing that gets complicated with pain is that there is frequently, often, a signal coming in from your body that is driving it, but not always. Where things went awry in all of this and where there was a lot of misperception, I usually blame it on Rene Descartes.

He's not probably fully responsible, but he was a 17th century French philosopher who is responsible for many of the modern aspects of philosophy. He also came up with Descartesian geometry, which we still learn in school. But when it came to Paine, he really screwed it up because he represented pain in this dualistic model where there was a direct link from your body to your mind. And that was the problem is that there is no direct link that your experience of pain is yours and yours alone. And that's one of the key things we learn as pain clinicians, is that everybody's experience of pain is different. And it's going to be different to the same stimulus. So just to riff off of this a bit, I teach the medical school classes at Stanford on pain and nociception. And so I frequently do a little demonstration in class. I have a circulating ice water bucket and I have them come in voluntarily. They dip their arm in

the bucket and they keep it there for 15 seconds. Y'all can try this at home if you want and do it with your family and friends. It's the same stimulus. And then they pull their arm out after 15 seconds. And then they whisper their pain score from zero to 10, where zero is no pain. 10 is the worst imaginable. And they whisper it into the ear of our research coordinator, like what they experienced. And then at the end of the class, I plot out their scores. And what it looks like is fascinating because everybody in the class experiences that same stimulus differently. Some people say, no, it wasn't painful at all. It was a zero, one. Some say it was a three, you know, a little bit painful. Some say a six, some say, wow, that was the worst pain I have

ever had. I could barely keep my arm in there. I do that because I want to teach these young physicians to be a clear message that pain is individual. It is unique to the person. And there's another message that's important as a clinician. We should never project our own experiences of pain onto other people and simply accept what they tell us when they come in and talk with us about their pain. So that's a little bit of grounding. Happy to go into that in more detail. So part of what I'm hearing you say is that, you know, like, let's say somebody, they wake up in the morning and they're like, oh, like my, my knee really hurts.

Like I, like there's, there's pain quote in my knee. But what you're saying is that's really not accurate. There's some stimulus coming from your knee. Maybe there's an injury tissue, something happened. That's traveling its way up through the central nervous system into your brain. And when it hits your brain, it's the brain that then says, oh, this stimulus, now we're going to tell you is the experience of pain. Is that sort of like roughly right? That is absolutely perfect. Okay. This is where, I mean, I love this field of pain because it's got so many dimensions and nuance and flavor to it, is that those signals that come up to the brain are now shaped by so many other things. They're shaped by, did we get a decent night's sleep last night?

They're shaped by how much anxiety or depressive symptoms we may have. They're shaped by our early experiences with pain. And so if you had early, you know, traumatic life experiences with pain, it actually sets up in your brain vulnerabilities to amplify things as an adult, which is why we need to be, you know be particularly careful about this thing of chronic pain and these injuries in kids, because it sets them on a lifelong path. It's shaped by our genetics. There are genetic vulnerabilities and sensitivities. It is shaped by various aspects related to sex. Women tend to be a bit more sensitive to experimentally evoked pain. What I mean by that is if you come into our lab and we cause an experimental stimulus of pain,

a noxious stimulus, women will report a little bit more. I think the press and the media make a little bit too much of that, honestly, because I think there's more variability within men and women than there is variability between men and women. But we all like to make big deals of small differences. So there's all these things that shape our attention and distraction to pain. Are we focusing attention on it? Are we in a state of relaxation when we're experiencing that pain? What are our beliefs about that pain in your knee when you wake up in the morning or in your back that you just mentioned? Let me give you an example. One of the questions, two of the questions that we ask at Stanford when patients come in, it's two of the probably the five most important questions we'll ask about people's pain. What do you believe is the cause of your pain? And what is the meaning of the pain? First one, straightforward. What do I mean by what is the cause? What do you think is causing your pain?

Now, when you mentioned your knee or your back, do you think that I worked out a little bit too hard yesterday and I have a little bit of inflammation there? I probably overdid it a little bit. Everything's fine and it'll settle down. Or do you think that, you know, you've got some terrible arthritis in your knee with bone on bone grinding away? Those are two entirely different belief systems about your pain. Building on that, what is the meaning of your pain? Do you believe that your pain is associated with actual tissue damage that's ongoing? So in the first case,

you were out running yesterday, you went for a long hike, you're just getting the usual post-hike knee pain, it'll go away. Or on the other hand, I have bone on bone arthritis. Every time I move, I'm grinding my joint away and it's getting worse and worse and worse. Why is that important to know? Because in the first situation, that person will probably take it a little bit easier that day, but know that everything's going to be fine. In the second case, that person is going to protect their limb. They are going to guard it. They're not going to want to move it. And if that goes on for a long period of time, that can result in disability, disuse, and dysfunction.

All for the same amount of pain experienced, by the way, but shaped by their beliefs and their understanding of their pain. And that's all about the same amount of pain experienced by the way, but shaped by their beliefs and their understanding of their pain. And that's all about the brain. Does the belief affect not only your response to it? So like whether you say, oh, I'll just kind of shake it off, take it easy today. I'll be back tomorrow versus, oh, something really bad here.

I need to just change my behavior and limit myself maybe for life. I see that. Does your belief about the source and meaning of the pain also change the way that we experience the intensity and duration of the pain in the moment? Absolutely. Great question. pain, what is going on out in your body is more related to injury, damage, and particularly if there's associated anxiety with that, if you're thinking about it constantly, your experience of pain is going to be higher than in that other situation I mentioned where you don't think it's injury causing.

You don't think that this is going to be long lasting and taking over your life. So what is the key message for people in this? One, one of the key messages to take home is understand the distinction between hurt and harm. Meaning, listen, life, life is pain. We're all going to have aches and pains through life. And we need to understand that that is unfortunately part of life. It may hurt, but those aches and pains are to be distinguished from something that truly is tissue damaging.

So understand when the pain that you're experiencing is actually associated with real tissue damage. And there is a need to protect that body part, whether it's your back, your knee that you mentioned. And that's where getting in the hands of a good clinician or starting off with a base of just self-education. Learn your body. Yeah. It's fascinating because as you're describing that, I was immediately reflecting on a number of years back, I broke a foot in my bone. So I was in an air cast and on crutches for the first time, I think in my life for six weeks. Yeah.

I couldn't put any weight on it at all. Yeah. After six weeks, I go back to the ortho, they take new x-rays and they basically say, you know, according to the imaging, you're fully healed. There's literally, you can go back, you can do all this stuff. He said, but because that foot hasn't been weighted for a month and a half now,

your connective tissue is going to be very different. And structurally, the first time you actually put weight on your foot, you know, we're gonna put you into physical therapy and it's gonna take a while. And what he said to me, he said, what I want you to know is that you're going to feel pain because remodeling the connective tissue and putting new

weight on this, it's going to be uncomfortable, but the pain that you're going to feel, he said, there's nothing wrong. There's nothing. When I look at your, your imaging now, you're fully healed, but you're going to feel pain. Part of what this work is, is over the next month or two through rehab, you're going to need to effectively keep using that foot in new ways and putting weight on it. And it's going to be painful for a while, but that's the pain of remodeling. That's a quote, good pain. So he was setting my expectations, which I thought was really fascinating. It sounds like that's partly what you're describing. Exactly. It sounds like you got partly what you're describing. Exactly.

It sounds like you got in the hand of a good clinician. And I can give you, that's a beautiful example. And I see patients in our clinic all the time where I can give you, you know, here's another one to build on that. A little bit of an extreme example, a guy in his 40s, he's an executive master's level tennis player. And he comes in on crutches. And he can't put any weight on his foot.

And the guy's depressed. He's anxious. Why? Because he can't play tennis. You know, tennis is his outlet. It is his meaning for life. And they have told him they can't find what's wrong in his foot. But it's, you know, it's getting worse and worse.

And he's just frantic. So do an evaluation on him. Find out it's something called a Morton's neuroma, which is just a big fibrous growth of around the nerves in your foot. And it's painful. Let me tell you, it's painful. But I told him this and I told him, listen, you're not causing your foot harm. You're not injuring your foot. You're not going to become crippled from this. And he just stared at me for about 15, 20 seconds. He just looked at me

while his mind was turning away. And he's like, you mean I can play tennis? And I'm like, yeah, you can play all the tennis you want. It's just going to hurt. And he's like, we're done here. And he just got up, left his crutches and walked out. And, you know, listen, that's an extreme example. Okay. And I want to go back to what I said earlier, which is you can never generalize these stories to other people. But that is one example of where tremendous fear and uncertainty and confusing hurt for harm caused a problem. Yeah. And the anxiety about, am I doing further damage by continuing to do this X, Y, and Z activity?

It sounds like it takes, it compounds the experience of pain. You know, it takes something where you'd be like, okay, so it hurts, but I'm not doing any damage. So I want to keep doing the thing that I love as long as it's not like causing any long-term things. And it sounds like your brain then processes the pain differently. The brain processes those stimulus. See, and this is where the problem with pain, we all get into this.

It requires a degree of precision of language or we start conflating terms. We all do it. I do want to make a point, though, because there's the flip side. There are people out there suffering from ongoing tissue damage, people suffering from degenerative conditions that are getting worse, who have tumors due to cancer, who have had traumatic injuries, who have chronic painful conditions that we can't figure out what the source of the nociception is. And I don't want to give people listening in this message that, oh, you can just come into my clinic and I'm going to

tell you you're not hurting yourself and everything's going to be fine. Because that's not the message. We're giving examples across this whole continuum of pain. And the reason I mentioned this is one of the biggest problems that I see in society, in the United States and globally, are that people feel invalidated about their pain experience. They're dismissed. And unfortunately, that burden frequently falls on women because in many of these conditions, we don't have a clear source of nociception. We can't put our finger on the thing and say, this is what's causing it. This is why chronic pain is often referred to as the invisible disease. And so these women, but also men, are frequently dismissed by their loved ones, their families, their friends, and unfortunately,

the medical profession. And the medical profession because we don't get much training in medical school and residency around pain. I think that's one of the key messages that I want to give is we need to validate people's experiences first. Understand that what they're experiencing is real. It is. I am not saying this is something all in one's your head. The experience of pain is something that is in our brain, though, that may, to some extent, be driven by these external signals that we call nociception being triggered. And what I'm thinking about is trauma, stress, grief, you know, like things like this, where if you ask somebody, you know, like my body is riddled in pain, I'm aching all the time.

Like my head is pounding. And I guess that's the question. You're like, can you experience this? It not actually be directly related to this process of nociception, can be based in something different. Yes. Extreme examples of that are things such as post-stroke pain. You've had an injury to a part of your brain, typically like your thalamus, and you experience terrible burning

whole body or hemibody pain and the absence of any peripheral nociception. But let's take it further out. If you've ever pulled an all-nighter, and those of us who went through medical school or who've pulled all-nighters, we know what it's like to go for long periods of time without sleep. I mean, you just feel like crap the next day. You ache all over. Well, there's probably nothing going on in your body as a whole. There's probably no increase in nociceptive signals. One of the key things, and I didn't tell this part of the story,

I mentioned these signals going up to the spinal cord and up to the brain where the experience occurs, pain, boom. But there's something else going on too. And we have signals that come down from our brain and they synapse or they connect in the spinal cord. And it acts like this big negative feedback loop. And what those negative feedback loops do is they turn down the signals coming in from the spinal cord. And in a healthy situation,

we've got this balance of yin and yang, if you will. The ascending signals coming up from the spinal cord. And in a healthy situation, we've got this balance of yin and yang, if you will, the ascending signals coming up from our body, the descending signals coming down. And in that healthy situation, we experience no pain. What happens with pain is we either have too much of the signals coming in from our body, or we have too little inhibition, those descending signals, too little of those coming down, and that feedback system's not working. And what that means is that you can have pain from normal signals in the absence of injury if your inhibitory system is not working right. Does that make sense?

Yeah, no, absolutely. And what we find, there's a condition called fibromyalgia in which we know that those inhibitory systems are out of whack, that people don't have that normal inhibitory tone that they should. Now, there's a lot more going on in fibromyalgia, but that is in part why, and again here, it's mostly women, it's also men, you can feel pain over your entire body in the absence of clear nociceptive signals coming in. So it's in part then, it's these inhibitory,'s going going awry in that inhibitory system or side of the system that helps balance out or tamp down i don't want to call them errant signals

because it sounds like what you're also saying is like every signal has information every signal has meaning and information a lot of those signals a lot of the information going on in our brain at any given time is to filter out stuff that's not important. You know, filter out extraneous visual stimuli that we're not focusing on, auditory stimuli. We're not focusing on how various parts of our body feel because at the moment in time, because you and I are talking with each other. That's all going on behind the scenes. And when that system gets out of whack, all of a sudden, normal signals become perceived as painful. And we have ways of treating that through medications, through mind-body approaches, through physical

therapy approaches. Let's go back to your foot. If we could go back to your foot for just a second, your clinician told you about re-engaging those connective tissue, right? And building those up because they weren't used to pressure. But there was to having those signals coming in on a regular basis. And so what you needed to do was retrain those nervous system components, those systems, back to where they were before the injury. And that's another reason why you felt pain. It's not just the peripheral tissues and the fascia. And I think that's a perfect example, once again, of where the clinicians, we all tend to look through the lens upon which we're trained. Your clinician was probably looked through a lens of tissues, right? And the thing with pain is it involves so many components.

And it's frequently like, what is that old Indian parable of the blind man and the elephant? You know, somebody feels a trunk and thinks it's a snake. Somebody feels a leg and thinks it's a tree. That's the thing with pain. To understand it, you really have to put all those pieces together

to see it's an elephant. Yeah, that makes so much sense. And we'll be right back after a word from our sponsors. whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you eight hours of charge in just 15 minutes. The Apple Watch Series X. Available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required,

charge time and actual results will vary. Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. i do want to drop back into this the notion of I don't know whether psychogenic or psychosomatic or whatever the proper phrasing is, but like, I'll give you an example. I had a friend, a really troubled relationship with his dad for years. He's a little bit further into life and he had migraines. My friend had migraines for his entire life.

His dad passes, the migraines go away. Sure, sure. There's greater appreciation for one, early life experiences impacting our experience of pain. Two, relationships impacting pain. And this is a big deal. And there are newer and newer therapies that are focusing on some of these relationship aspects and treatment in pain, these unresolved issues that they're just unconscious. We're not even aware of them until they're brought to the surface. Was your friend experiencing real pain? Well, absolutely. But this gets to what we were talking about before, where these brain circuits can get kind of mucked up. They can feed and take over, and you can end up with pain where there's no clear evidence of no

susception or minimal evidence. And again, that's where getting in the hands of a good clinician can go a long way to helping unpack some of that. There's a therapy these days called EAET, which gets at some of these relationship aspects and some of the challenges and some of the emotional awareness aspects of pain and treating those. I think the key thing in all of these and where we're still lacking in the treatment of pain is we don't yet know how to target the right person for the right treatment. So frequently somebody like your friend goes through this long laborious trial and error process of treatment after treatment, after treatment, until they find something that works in this case, the unfortunate passing of family member.

The subjectivity of all of this is fascinating, explains a lot. And also I would imagine incredibly frustrating in a lot of ways, both for the, an individual who experienced pain, I would imagine for a practitioner also where you're really going on a journey of discovery along with someone who walks in because what's obvious or what seems like might be on the surface, you know, you just got to keep peeling the onion. I mean, another thing that comes to mind for me is the person who has an injury, they experience pain a couple months later, the injury is healed. They take me with like the foot thing, right? I go through physical, I go through rehab, functionally, anatomically, physiologically, like everything looks like it's good to go.

What happens with some folks is that the pain never goes away. So what's actually happening there? When the pain starts acutely, and then in theory, everything that needs to be resolved is resolved, but the pain remains. Yeah. And this is one of the challenges that we as a medical and scientific community are continuing to face right now and putting a lot of research effort in to unlock the mysteries of that. People refer to it as the transition from acute to chronic pain. The notion that for a percentage of people, their pain doesn't go away after an injury.

And it's a problem that's only getting worse in society. Why? Well, one, we're living longer. And so the very notion of living longer and being exposed to more injury and stuff, there's more chronic pain. Two, we're getting better at keeping people alive. So, you know, you look at motor vehicle accidents. We can get people to hospitals and treat them pretty quickly. We've got great surgeries. Same thing with wartime. You know, we can get them off the front lines. But now you see these men and women coming back whose bodies have been, you know, repaired, if you will, to the best extent possible, but they're still left with terrible chronic pain.

We have great ways of treating cancer now. It's gotten much better. But the treatments for cancer, frequently it can leave people with persisting pain from the radiation therapy, the chemotherapy. So what is going on here? The short answer is we don't have the answer to all these questions. We know that unfortunately, there is a vulnerable population. We don't know how much of this is genetics, how much of it is what you bring into that injury that sets you up for persistent pain. What I mean by that is there are probably some genetic predispositions that we can't control, but we can identify. There, we do know that when you come into a surgery or an injury, that what you bring into that injury or surgery often has more to do with whether you're going to have persistent pain than the injury or the surgery itself. Meaning,

if you have high levels coming in of depression, of anxiety, history of PTSD, big one, that's a big one. You are set up to be more vulnerable to have persisting pain after that injury. And the reason is those brain circuits, they're out of whack, to use a colloquial term. But they're sensitized, and they get wound up. We know that there are factors that impact those brain circuits. And then we also know that there are in some people, these molecular triggers and systems in the body and the periphery and in the spinal cord that don't go back to normal. Let me give you kind of an analogy, if you will.

I think you mentioned before the show that you've been dealing with a little bit of a cold. As longtime listeners will hear in my voice, I'm definitely a little more bassy and gravelly than normal. So what happens in that cold? Well, what happens is the cold viruses activate, in part, glial cells, typically microglial cells that are non-neuronal cells that are in our central nervous system and elsewhere. And those glial cells release all sorts of chemical mediators, cytokines, histamines, bradykinins, interleukins, blah, blah, blah. And it's an inflammatory soup. Think of it as a inflammation soup. And that inflammation soup during your cold, and the same applies during an injury, after surgery, after an injury,

puts into play a healing process. It brings to bear all of your immune system to come in and fight the offending agent or to repair the damage that was done. But part and parcel of that is something called the illness or sickness response, which means, Jonathan, I appreciate you're here and you invited me on your show. But part of you probably wanted to just sit on the couch with a blanket and have somebody bring you the hot cocoa with those little marshmallows on it and just kind of rest up because that is hardwired into all of us when we get a cold, but also when we get an injury, that inflammatory soup occurs. Now the good news is the tissues heal up. The inflammation and that inflammatory soup that goes away and we go back to business as normal. But in some people, it doesn't go back to normal. Those switches don't turn off. The neural inflammation continues and we're left with chronic pain. And they still have this urge to kind of isolate from other people and to sit on the couch and have somebody bring them the hot cocoa with the marshmallows. And we're still trying to figure out why those switches don't go back to normal. It's a fascinating area of research and there's therapies

that are being more and more aimed at those glial targets. You use the word switches a number of times there, which whenever I hear that word, for some reason, something in me often associates that with epigenetics now. A lot of people have this rough notion of epigenetics as if we have our genetic code, but that doesn't necessarily determine our lived experience. Whether certain genes are switched on, switched off is much more about how we experience the world, how we move through the world. I'm wondering whether there's an epigenetic element or component to any of this.

Yeah, almost certainly. First of all, the geneticists out there are going to disagree with me, but I think the actual amount of genetic contribution to this of the development of chronic pain is probably really tiny. It's probably really small. We've yet to find any direct heritable genetic single and nucleotide polymorphisms. We refer to them as SNPs, any single genes that are responsible for these chronic pain conditions, except in rare, rare situations that are kind of cocktail party discussions. Arithromelalgia and congenital insensitivity to pain that makes for great movies. But in the real world, one, it's polygenic, meaning it's probably a contribution of multiple genes, and even then, only small contributions.

Now, layering on the environmental influence onto your genetics, that's where probably the real action is. And so this is getting back to what you suggested. And I think the good news in that is that there's no life sentence per se that's been handed down by our parents and the genes they passed on to us. We are in control of our destiny. For the vast majority of cases, there are rare exceptions. One of the other things that pops into my head, and I do want to kind of transition into some of the ways that we're treating pain and what the future looks like as well. But there's one other thing that is sort of sitting there with me, which is I think epigenetics has become a bit of a buzz word these days. But there's another buzz word that I think has been floating around a lot, which is microbiome or the enteric nervous system. This notion that the nervous system isn't just about your spinal cord and your brain, but there's a whole separate system.

And a lot of it is in some way manipulable by all the critters that live in our gut. And I'm wondering what your take is on whether that actually has an influence on our experience of pain. Oh, absolutely. It's an incredibly new, untapped area for us to understand, research, and ultimately treat in pain. And the problem I think we have right now is that there's more we don't know than we do. And so let me just preface by saying, yes, we know the microbiome

is playing a role. And I invite people to be careful about the messages out there, because in these phases of new research and new understandings, sometimes they get oversimplified. And sometimes also people, enterprising people will try to take advantage of that and sell things, snake oil to do that when there's, we don't have a lot of data yet. We do know more and more that the enteric nervous system, the nervous system of our gut is directly communicating with our brain. It is shaping our experience of pain. I've had a personal experience in this space. I used to be able to eat anything, absolutely anything. And I took our group out for a happy hour one night about 10 or more years ago to a

Mexican restaurant and I got food poisoning. And that changed my life forever because after that episode, I could no longer get near an onion without severe debilitating pain for about a week, sometimes two weeks. And it messed up my sleep. And when my sleep was messed up, this is again that link between sleep and pain. It messes up your cognition and your overall quality of life. And it took me a long time to figure out what was going on. And I was able to find answers probably because I'm a pain physician. I'm a pain physician scientist and I researched the heck out of it. There's no treatment for this per se. I do avoidance and I'm fine. But clearly something was altered within the gut and my gut's response to an onion as an antigen, as a substance, which is no longer viewed as normal, but as

abnormal. Now that's one example. I think we're going to find that there are plenty of others. There's a great interest in these anti-inflammatory diets, which is a broad umbrella term. There is undoubtedly something to it. The key is, once again, to figure out the right, if you will, diet, dietary modifications for the right person, their painful condition, and their specific circumstance. It's so fascinating. I feel like we're in this moment where we understand a lot more, but it's almost like the more we understand, the more we're starting to realize the vastness of what we don't understand. And maybe that's new to me. Maybe you've been living

in that world for a long time now yourself. All I can tell you is back in my 20s, I used to be a lot smarter than I am now. I think we all are. I think I keep getting more and more stupid as I go along. Because the more I know, the more I realize, oh my God, there's so much I don't know. And we need to learn. The good news is our knowledge is growing. We are learning more and more about this condition of chronic pain. Yes, the microbiome, my prediction is going to be a key player in this. I think it'll be a

key player like much of the rest of what we described earlier in our discussion is, meaning when we're talking about treatments, it's going to be rare where we find a magic bullet for a chronic pain condition. It occurs. It can happen. I love those times when somebody comes in and I can do a nerve block or single medication or a single treatment. Boom, they're cured. We all celebrate those. Usually it is a team-based approach where we're applying multiple therapies to go after those pain processing pathways from the periphery or body, the spinal cord, the brain, those descending pathways, and doing that all together. And we'll add on the gut. That know, that's going to be another approach, clearly.

Yeah. It's interesting because on the one hand, I can see, well, you're just, you're trying to basically attack any possible contributor from all the different directions. Because at the end of the day, you know, especially if you're dealing with a patient in front of you, the ultimate outcome is for you as a scientist, you want to learn something, but for them, they just want to stop hurting. So it's like whatever it takes. I would imagine a lot of people, they don't entirely care the complexity and what are the eight different contributors to this. They're just like, can you help me feel better?

But on your side, it's like, but I also need to try and understand what's happening here because I'm going to see thousands more of you. And the more that we can understand and share this knowledge, the more we can start to really understand how to help any given person more quickly and more fully. Well, that was beautifully put up. You should just run the show. I mean, that was great. You are so right. That's why we play these different roles. As a physician, my job, my calling is to help the person in front of me. And you're right. The thing about pain is that it is being this harm alarm. It is incredibly distressing to them. They just want to be out of pain. They want to stop suffering. And particularly with pain that's with you 24-7, it just wears you down. It sucks your soul. And often you're right. They don't care what the treatment is. They just want something that'll take that away. And I get that. And that's what we move towards. And you're right. The scientist in me wearing the other hat wants to understand why they're experiencing it, not only to help the person in front of me, but hopefully

to take that knowledge to help others so that we can come up with safer and more effective treatments for the next person that comes into the clinic. That's where we're going with the science is to try to collect high quality data on many of these people to better understand. But in the meantime, you're right. When I'm seeing patients in the clinic, it's one at a time and it's helping them with their unique problem and everybody's different. I think when people think about how do we treat pain, and again, we probably need to make a distinction between acute and chronic because I think there may be more obvious ways to treat acute. There's the traditional rest, ice compression, elevation, although I guess parts of that are now being debated. There, you know are the OTC, the NSAIDs, and then the prescription

things that I think many people are going to be familiar with, and to varying degrees of effectiveness, and each one with varying degrees of risks also. And I feel like increasingly, chronic pain has become the focus of so many people. And as you described earlier, oftentimes you show up and there's no clear, no secession process that we can point to, which is if mindset and anxiety and fear are part of your experience of pain. If somebody tells you, I can't tell you where this is coming from, that's only going to increase the, well, maybe I'm making an assumption here. I would imagine for a certain group of people,

that's going to increase the experience of pain is the lack of knowledge. Well, nobody can tell me where it's from. Now we add frustration and futility to it. And then the concern that I'm not going to be believed if somebody can't point to it. So everything sort of compounds there. And I feel like chronic pain has really become such a pervasive experience. And as you described, we're living longer.

There's more opportunity for it. We're living through some interesting times also, which I think creates more opportunity for it. When you think about the state of how you're treating things now, what are you seeing as being more broadly effective for a lot of people? Or is that the wrong question? The real question, there is no broadly effective and we shouldn't be looking for that. We really need to take people one by one. Great question. It might help to start with the foundation of how we treat somebody with chronic pain. And I'll share with you,

you brought up acute pain before. What we're finding, by the way, is a lot of the treatments for chronic pain are making their way into the treatments for acute pain. We're finding that they work quite well, particularly some of the mind-body approaches, some of the medications that we used in chronic pain also can be effective in acute pain. So it is blending or blurring more and more. And a lot of that with the idea of trying to reduce those people with acute pain going on to develop chronic pain, in addition to trying to get people back to their activities faster, focusing on chronic pain. I think of six, if you will, pillars, categories of how we approach people with chronic pain and treatments. One is the medications.

Two are the procedures, interventional procedures. Or three, mind-body therapies., four physical and occupational therapy approaches, what we used to refer to as complementary or alternative medicine approaches or integrative health approaches, and six is self-empowerment. probably have about 200 or so different medications that have shown some benefit in pain. That's a lot. Most of those are not opioids, by the way. Only about 20 of those are opioids. But people frequently conflate or think of chronic pain with opioids. Opioids can play in a role. The point I'm bringing up is there's a lot of medications out there available.

Two, interventions or procedures. We have probably over 200 different nerve blocks and other interventional procedures from trigger point injections, different nerve blocks, all the way up to spinal cord stimulators and implantable drug delivery systems. Three, mind-body approaches that run the gamut from classic cognitive behavioral therapy approaches, mindfulness-based stress reduction approaches, acceptance and commitment therapy approaches. And there's newer ones like, you know, my partner, Beth Darnell, developed something called Empowered Relief, which is a brief behavioral intervention. For physical and occupational therapy approaches, we're all

familiar with it. These are building up strength, endurance. It's teaching people pacing approaches, which we can talk about if you want. It's helping people learn some of the distinction between hurt and harm and understanding their body. Five, the complementary alternative medicine approaches, acupuncture, over-the-counter nutraceuticals. I'm still using that term. I'm not sure if that's even the most contemporary one, but it's the vitamins, the supplements that you go buy off of wherever. There are a number of those that have been shown to be effective for pain that are over-the-counter in this country that are actually prescription agents in other countries.

And number six, which is probably the most important one. I didn't mention these in a particular priority, by the way, but number six is self-empowerment, which is it all starts with getting educated, with learning your body, with learning your painful condition, and using that knowledge to empower you. So that's the way that we kind of approach the buckets, the pillars, if you will, of treating chronic pain. There are others, but that's broadly how we think about it. And it is a matter, it is the issue of putting the because, unfortunately, a lot of the data out there can't direct us and say, this treatment will work better than that treatment for this particular condition. We have just general guidance.

That's where a me because the order that you shared them in feels like it's also, there's a bit of a correlation with the timeline that it takes between intervention and relief. And maybe that's wrong or right, but sort of like, you know, it's the more immediate interventions, even if they're not full. And then like down on the other end, we have self-empowerment, which you say is like maybe the most important one, but that's not an overnight thing. You know, this, this is like, you know, it's knowledge building, it's practice building, it's, it's skill building. I wonder

whether we look at that last one, we say, oh yeah, yeah, yeah. Self-empowerment. Sure, sure, sure, sure. But give me like, give me the shot or give me the procedure or give me the pill because like, that's going to help me now. And we're doing ourselves a disservice by focusing more intensely on the instant moment. And again, would never blame anybody for wanting to be out of pain now, of course. I've been in that moment and we all have. But oftentimes I think when this stimulus for pain stops creating pain in our brain, the motivation to do the work for something like CBT or self empowerment becomes greatly diminished until the experience of pain comes back. That's the way we're wired, isn't it? Isn't that something? You're right, the self empowerment

aspects not only can help us in our pain now, but they set up skills for the future. And I'm sure you've had many guests on your show that have talked about these mind-body approaches, but they apply to things outside pain, depression, anxiety, stress, sleep, you name it. They're basic skills building. We should teach this stuff in schools, honestly, and have our kids better prepared for inevitable stressors and pain that occurs in life. And you're right, it is probably the most important one. And the people that I see that come into our clinic, because we're what's referred to as a tertiary referral center, we tend to see the really complicated patients who've already been through a lot. Yeah, they want something right now.

What we try to do is put it all together. You know, we don't do just one thing, but do it all and integrate in that self-empowerment with it. Yeah. And we'll be right back after a word from our sponsors. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist,

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Y'all need a pilot. I'm wondering where you see in the six pillars also, for lack of a better word, attentional control, you know, agency over our attention falls. And what's coming up for me is I remember for, in a past life, I was a yoga teacher. For seven years, I would step onto a floor a couple days a week. And for 90 minutes, my job was to take 50 human beings and make that 90 minutes worthwhile for them because we were in New York, we were moving fast. And it was, I had an obligation, a responsibility, a noble responsibility. There were plenty of times where before I would step into that room, I had a pounding headache and I didn't want to go. I didn't want to do it. But I had this repeated experience of,

I would get in there and I literally would hear the latch on the door closed behind me into the practice room. There, you know, all these people sitting on their mats waiting for this to begin. I would sit down. Within a matter of three, four, five minutes, I'm teaching. And for the next 90 minutes, I don't functionally, I don't have a headache. The moment I bring people out of final relaxation, Shavasana, and the last person leaves, I have a headache again. And so it got me really curious about the role of attention and pain because my attention was hyper-focused on a room full of people. Like I

was there, I had a job to do and I was really very intentionally present with them. My attention was with them and it made it all, if I was doing quote, doing my job, it made it hard to focus on what was happening inside of me. But the minute that job was over, I was back. So I'm curious about the role of attention in the experience chronic pain. And what you described is a beautiful example of where it works. And we often work to get people engaged in activities that will be distracting, walking, exercising, reading books, particularly engaging with friends and family. Because one of the negative aspects that we're more greatly appreciating is that people withdraw from social engagement. Where that fits within the pillars, it actually fits into multiple ones. Different forms of psychological interventions, for instance, acceptance and commitment therapy and mindfulness-based stress reduction, both have some components of how do you interpret when you're experiencing that pain, that headache? Do you focus your attention on it? Do you think about it?

Or do you just kind of accept it and be aware of it in a nonjudgmental manner? And from a pain standpoint, those are skills that can go a long way. I'm grossly oversimplifying this, by the way, for the sake of a story. Next, this is used extensively within physical therapists. And they help people with, again, setting goals, getting them active, doing things that will be distracting for them. Next, I mentioned complementary alternative medicine, which may not be the best term. I kind of put yoga into that. And actually, there's good data, by the way, on yoga and back pain and yoga and other chronic pain conditions. And yoga, perfect example of that.

And then lastly, that self-empowerment, recognizing, Jonathan, what you just said, you recognized that thing, you learned from it. So those were skills that you could use to take forward. well during the daytime. I think where they start to break down is at night when we're trying to sleep. And that's something we still need to work on because people are just staring up at the dots on the ceiling. It's hard to distract yourself away. And then when your sleep gets out of whack, as we talked about, you feel more pain and gets into a vicious cycle. So there's a clear opportunity there for improvement. As you look at the work that you're doing right now, because you're involved in the research side of things as well, when you look at the next five years, the next 10 years, what's really exciting you in this domain? Yeah, I'm jazzed about the future right now and the opportunity to improve the lives of large

numbers of people. So my research wears a couple hats. One is I'm a neuroscientist who studies a human pain condition using a number of techniques like functional magnetic resonance imaging, sensory testing, and published a number of papers to understand mechanisms of pain, individual differences in pain, the impact of brain circuits on pain, and translate that into therapies. And that's one hat. And right now where we're moving into is the development of objective biomarkers for pain. Now, what I mean by that is, as we talked about, pain is a subjective experience. But what we need are biomarkers that we can develop to predict what treatment will work for which person. I don't mean biomarkers to determine if somebody's

in pain or not in pain. I can always just ask somebody. But we want to know, are there markers, physiologic or otherwise, that will help us predict, are you going to respond to yoga or an NSAID or a nerve block? That's where the field needs to go. And that's where a lot of our research is right now. Second hat, for the last 20 years, I have been working to collect high quality data on real world people with chronic pain, because we need to learn from each and every person. So I've built an informatics platform. It's called Quire, which we've put into multiple clinics, pain clinics,

and it captures high quality data on people with chronic pain. And we're using that data to pattern classify and to understand the person in front of us so that it can help us guide treatments. And where things are exciting for me is one, blending that learning health system that I've developed with the biomarker work that we're doing. And then there's one last component to it. And that is my partner, Beth Darnell, who's also a professor in pain. She is a pain psychologist scientist. And what Beth has developed are these brief behavioral interventions. Brief meaning in cognitive behavioral therapy, which I know you're very familiar with, it's typically eight weeks. Eight weeks. People hate to say it. They frequently don't want to go to it. They're working. They're busy. It's hard to get them grant right now to spread this throughout the country.

What we've shown with the NIH grants is it works as well as cognitive behavioral therapy. We're not looking to replace CBT. But we want to develop systems that can translate, scale, and make them more available to others. The problem we have in society is that most of the major pain centers are concentrated in small clusters in the country. You know, I live in California, in the Bay Area. You just go 30, 40 miles inland, that's farmland. It's just a huge swath. It is a healthcare desert out there, and people can't get good quality care. And so we're extending, we're taking this work, this digital health platform, we're putting it out into a national cloud-based model under a nonprofit.

And the idea is to collect high-quality data on people with pain, lived experiences with pain, and be able to deliver effective, brief behavioral treatments and other treatments. And what motivates this is, in part, I co-led the development for our country, the National Pain Strategy. This was for the U.S. Health and Human Services, and we put this out in 2016. And one of the strategic goals was to develop such a platform. And you'd be surprised, nothing exists like this. So that's what's exciting. It's bringing together 20 years of my research, Beth's decades of research, bringing all this together into something that our goal is to really help large, large numbers of people out there. Thanks for asking.

You ask a scientist what they're excited about, we'll ramble on forever. No, it's fascinating because what you're describing is effectively working to democratize not just education, but modalities that would potentially help millions of people who don't necessarily have access to these major pain centers or leading researchers. Or you're basically saying, we've done a lot of work for decades now. We figured out some really interesting stuff. We don't know it all, but we've got some insight that I think would be really valuable to a lot of people in a lot of places. So let's figure out how to share it. Let's distribute that rather than hoarding it. Perfectly stated. We're all

striving in research to come up with the next new treatment. And we do need new treatments for pain. But the thing is, we've got a lot of treatments out there, a lot of things that actually work. And we just need to get them in the hands of people and make those available and cost-effective or free. So one other thing popped into my head before I let you go, which is you were hearing a lot of stories now about AI in medicine, especially on the being able to identify potential existing molecules or pharmaceuticals or drugs or supplements or nutrients for use cases that maybe we didn't know about or entirely new

things. Do you have a take on the role of AI in the future of pain research and treatment? Oh, it is. It is going to be a huge part of the future. My crystal ball is a little bit cloudy. As all ours are at this point. Yeah. So I think anybody who comes in and tells you they've got the answer, I would be questioning that because the field is just moving so fast. We are deeply involved in using large language models, generative AI approaches within our research and building tools within our clinic. I do know that I don't think that these AI tools are going to put pain docs or other docs out of business, but I think that the docs that don't use them will be out of business. I think from augmenting our clinical care, they're going to be invaluable and allow us to do things better.

From a research standpoint, I see some incredible opportunities, and we need to be rather thoughtful about how we apply them. Let me just give you a simple breakdown on this. We have these models, these AI models that are interpretable and AI models that are black boxes. You're familiar with this. So black boxes mean we don't know what the heck is going on inside. Now, as a physician, we are probably not going to trust an AI system that just gives us an answer and we don't know where the heck it came from. But we will trust something that just gives us an answer and we don't know where the heck it came from. But we will trust something that just gives us a suggestion or an idea. I think the key for us is to use these

AI models where they provide interpretable results. We can look under the hood, we can see what's going on and understand those factors that are contributing to its decision-making. I'm particularly excited about that. In finding insights into our research data, I've been impressed with some of the AI models on our brain imaging data and some of our biomarker development. So all I can say is it's an exciting time. We need to take some care

and being cautiously optimistic, appropriately skeptical, and using these tools as wisely as possible. I don't know what, Jonathan, what are your thoughts? You've been, you've been probably asking that question to a lot of people. Have you gotten any, any clear definitive answers? Pretty much anyone who I trust has said, it's fascinating. We're using it and we're holding on for dear life. And we have no idea where it's going to take us at this point. It's like you wake up tomorrow, it's like, oh, it's something new. Wow. But it is. I mean, I think of any application that I've talked to people about or seen it involved in the applications in various parts of medicine to me are where I

just see potential for really stunning acceleration of ideas and me are where I just see, you know, potential for really stunning acceleration of ideas and solutions and interventions and just knowledge happening. And like you said, you know, we also need to be thoughtful and ethical and cautious and keep people in the middle of this whole experience. So I'm excited, you know, for where it's all headed. It feels like a good place for us to come full circle as well. So the question I always wrap up with everyone in this container of good life project, if I offer up the phrase to live a good life, what comes up? I am living a great life. So I have a life, Beth and I live on top of a mountain where we work darn near every day. And our work is tied in with our life and our mission.

And we're both committed towards improving the lives of people in pain. That's why we were put on this planet. And at the same time, every day she comes down and drags me out into the forest, and we go for a forest hike for an hour and a half or so and walk in the trees. And it's a creative time where we can talk about our lives and also about pain. And then we come back and do more. And so, you know, I recognized what a blessed life I have. I come from a very working background and person, only person to go to college, I think. So I'm appreciative of the gifts that have been given to me.

And I just want to put those to good use. And Beth feels very much the same way. So I think it's having that meaning and a purpose and a way to, at Stanford, execute on that purpose to make a difference. Thank you. Hey, before you leave, if you loved this episode, say that you'll also love the conversation we had with Dr. David Siegel about the science of longevity. You'll find a link to his episode in the show notes. This episode of Good Life Project was produced by executive producers, Lindsay Fox and me,

Jonathan Fields, editing help by Alejandro Ramirez, Christopher Carter, Crafted Hour Theme Music, and special thanks to Shelley Adele for her research on this episode. And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app. And if you found this conversation interesting or inspiring or valuable, and chances are you did since you're still listening here, would you do me a personal favor, a seven second favor and share it maybe on social or by text or by email, even just with one person, just copy the link from the app you're using and tell those, you know, those you love, those you want to help

navigate this thing called life a little better. So we can all do it better together with more ease and more joy. Tell them to listen. Then even invite them to talk about what you've both discovered because when podcasts become conversations and conversations become action, that's how we all come alive together. Until next time, I'm Jonathan Fields, signing off for Good Life Project. We'll be right back. You know what the difference between me and you is? You're going to die. Don't shoot him. We need him. Y'all need a pilot. Flight risk. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever,

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