Sean Mackey, M.D., Ph.D.
Appearances
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Exactly. Muscle relaxation.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Part of the challenge was, and now I'm starting to step outside of my wheelhouse, even though I was a member of the anesthesia tribe for a long time, is the levels of volatile gas anesthetic that you need to necessarily obliterate reflexes and full nociceptive impulses would be so high that it would depress one's blood pressure. And so you augment that with an opioid. Understood.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
like fentanyl, like morphine, like whatever, and you combine those together, and that's why what the anesthesiologists do is quite magical.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They're working synergistically, and they're working at different mechanisms. Got it. And during that process, the patient is not feeling pain, If they're unconscious, because you do need a conscious, working, aware brain to feel pain, but all of the electrical impulses coming in from the body that are slamming into the spinal cord and the brain are open full bore.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They're impinging on all those brain systems responsible for stress responses.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yes. And in response to nociception. independent of perception of pain. Right. And you notice that I'm trying to be precise in my language here, because since they're unconscious, there's no pain, but there's plenty of nociception.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's exactly it. It's remarkable through modern medicine that we get people through all this as a reflection of advancements in surgery, advancements in anesthesiology, advancements in post-operative care. But it is no different than a controlled injury. It's done in a nice sterile environment, but it is a massive injury that people are undergoing.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They're just not awake, and it's nice and clean and sterile. But there is a stress response associated with that. Most people recover well. One of the hot topics of research these days is why do most people recover, but a certain percentage of people go on to have persistent pain after surgery? That's an area that I used to research years ago. Many others are doing some great work in that space.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Turns out that a lot of the factors we're going to get to this is what people bring to your operating room table, meaning early life events, levels of emotional health, cognitive health, and everything else. So to answer your question and getting back to it, no, I don't believe there is the perception of pain without a conscious brain. There's all sorts of nuances to that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So what does that mean? That's where it gets muddy. And there's smarter people than I that would probably be more articulate, but This is why I think on first principles, you have to define the thing that you're talking about. When we typically talk about pain, we're talking about it from a uniquely human standpoint. Does a dog experience pain? Easier to accept. Easier to accept. I'm a dog person.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They experience pain. You move on down the evolutionary. At what point?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You see how muddy it gets. You go down rabbit holes pretty quickly, which is why I tend to stay with humans, which is hard enough by the way.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So we have different ways of categorizing pain, putting it into different buckets, if you will. One is nociceptive pain. And you'll note that That word nociceptive sounds very similar to nociceptors, and it's by design. It means that it is pain caused by activation of primary nociceptors, whether it be in your skin or soft tissues or viscera. and it tends to have certain qualities.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's very easy to localize. You know exactly where it is. It has a certain intensity. That nociceptive pain tends to be time-limited, responds well to short-term use of analgesic agents, acetaminophen, NSAIDs, COX-2 inhibitors, opioids, and it tends to go away. And this is the kind of pain that occurs after typically acute injuries. You then have visceral pain,
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
which as a former general surgeon, you understood this. This is due to activation of those primary nociceptors in our viscera. Now, the difference and why we bring up the distinction with visceral pain that is either in our thoracic viscera or abdominal or pelvic viscera is that the receptive fields, that means where those nociceptors serve and what we perceive are very diffuse and wide.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
When you get a stomach ache, you can't put your finger exactly where it hurts. You tend to put your whole hand over it and say, it hurts here, it's diffuse. That's because the spinal cord and the brain have these diffuse receptive fields which expand the area. The viscera don't typically respond to the same type of stimuli that nociceptive pain does.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You'll remember when you were taking a bovie to the bowel, the small intestine, patients wouldn't normally move because the nociceptors don't respond to that. But if you tug on it, if you pull that- Or inflate it. Or inflate it. Boy, oh boy. Blood pressure goes up, heart rate goes up.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Interesting characteristics with visceral pain is there's something called viscerosomatic convergence, meaning that the afferents, the information coming in from the gut, from the thorax, converge with the same sensory systems from the rest of our different parts of our body. So you may remember the old medical school adage, C345 keeps the diaphragm alive. Okay. We all had these in med school.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, that means that the third, fourth, and fifth cervical nerve roots subserve our diaphragm, which help us breathe. When the general surgeons or others are operating and they get blood under the diaphragm, it irritates the diaphragm. And what patients will typically complain of, shoulder pain. because the shoulder is subserved by the fourth and fifth cervical areas.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so when they had shoulder pain, the answer wasn't something's wrong with their shoulder, it's they had some irritation of blood under there. It's why when people have a heart attack, pain radiates out into the arm because you've got the upper thoracic nerves subserving the heart that overlap the with the nerves that go down your arm and the nervous system gets confused.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And that's how it's expressed. And if you like the neurosciences, it's all pretty cool. If you're experiencing it, not so cool. Let's get to neuropathic pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Typical analgesics can be helpful, but identifying visceral-specific anti-nosusceptive drugs is still an area of hot research. These days, it's more about trying to identify the causes of visceral pain and reducing substances that are winding those nosusceptors up. Neuropathic pain, another bucket. Neuropathic pain means injury to either the peripheral or the central nervous system.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The nerves out in the body, it's either injury or dysfunction too. Nerves out in the body or the nervous system in your spinal cord or in your brain. Classic, you get nerve injury from a trauma from surgery. Classic qualities people describe burning, sharp, lancinating, stabbing, shock-like. This is the kind of pain that some people tragically get after a thalamic stroke in their brain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Half their body's just like terrible burning pain and there's nothing going on out here. It's all central. This is the kind of pain that you get and you experienced. with radicular pain. And radicular pain means, in this case, injury to a nerve root coming out of your spine.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's this sharp radiating pain, if you've got it in your lower back, that radiates down your leg, typically below your knee into your foot. This can be very challenging to treat with common analgesics. We tend to draw upon different categories of medications for this. These are, broadly speaking, anti-neuropathic pain drugs. And here, in our field, we steal from everybody.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There's only a few FDA-approved medications for pain, like a handful. So what we've learned to do is to steal, borrow drugs from the neurologists, their anti-convulsants, their anti-seizure medications. The gabapentinoids, the tegratols and their derivatives, their other anti-seizure medications, because they tend to have mechanisms of action that also work on nerve pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Gabapentin, I think you've had perhaps some experience with. Turns out it's a lousy anti-seizure drug. Terrible. But it's a pretty good anti-nerve pain drug. Four grams a day. Four grams a day. Yeah. Drowsy though. You know who gets credit by the way? I give credit to making gabapentin the blockbuster drug. George Clooney. How? You ever watched ER? Yeah. He was a pediatric ER doc.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Kid comes into the ER with a skateboarding injury. George Clooney puts the kid on gabapentin. Now, where that had all started was a case report from a couple of ED docs who had noted by putting people on gabapentin that their acute pain got better. So,
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I felt like beforehand when I was practicing medicine, around the time I saw you practicing pain medicine, that I'd look like a genius if I put somebody on gabapentin because nobody heard of it. And then after that came out, floodgates opened, primary care docs started using it. Now everybody's tried it. And it's a very safe medication.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I should also make a mention when I'm talking about these meds or any treatments. I have zero industry relations with anybody. Nobody. I don't take any industry money. You can go look me up on Open Payments CMS, which is a public database. Okay. Neuropathic pain. There's another one. There's a new kid on the block called nociplastic pain. I don't know if this one has made much traction yet.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This is a newly introduced category of pain, which is thought to represent dysfunction in the central pain processing system. And I'm not precisely defining it, but that's the gist of it. It means that in the absence of an identifiable peripheral cause, There is dysfunction in the brain and the spinal cord that is causing pain, perpetuating and amplifying pain. Nociplastic pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it has been tied in with conditions like fibromyalgia, temporomandibular disorders, some aspects of chronic low back pain, irritable bowel syndrome, interstitial cystitis, and more. It's slowly starting to get traction. When we talk about pain, both to study it, but also ideally to treat it, we put them in these categories that we just described.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You're absolutely right. And I think the verdict is still out. In the end, does nociplastic pain stick around? Or is the problem that in these conditions that we associate with nociplastic pain, medical science hasn't caught up to identify a specific peripheral driver? I'm of the opinion it's that latter. I think we're going to find peripheral drivers for fibromyalgia.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There's some controversy right now as to whether fibromyalgia represents a small fiber neuropathy. And just because we may not be able to identify a lesion doesn't mean that there's not something there. But, as in all things, the truth will weigh out. We'll see how the story plays.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Oh, the last 15 years of my career has been spent on doing that very thing. And where do you think we are in that regard? Much further along than I ever would have predicted. So a large chunk of my research early on, my early research was in neuroimaging of pain. It was opening up windows into the brain to see where people were thinking, processing, perceiving, magnifying pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I spent much of that publishing work to understand the mechanisms of that. And we haven't yet actually finished our story of pain going up to the brain and what's going on. And we'll get there. Over the years, I migrated into the space of developing objective biomarkers of pain. So I love working with young, smart people. I bet against it.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I had some young grad students and others who said that they thought they could do this. I told them how you would do it. And I said, it won't work. And I'm going to pay you. I'm going to give you money to go scan people. And you're going to learn how it doesn't work because failure is a great lesson in life. And they came back and they showed... they could do it.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it was all through developing patterns in the brain and using machine learning models to then take that pattern, that signature, and be able to predict in other people whether they were experiencing pain. I didn't think we could do that because of the hugely individual nature of pain. It's so different from person to person.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But it turns out that there are core patterns in the brain that represent that experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
FMRI? Functional magnetic resonance imaging. It is a standard MRI that people go into, but we do some fancy pulse sequences. We play some physics tricks where we can see where nerves, the brain's being activated. And we've taken this, we and others have taken this from being able to determine whether somebody is in a state of pain to predicting their long-term trajectory.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We're working right now, a big grant that I have is to actually create composite multimodal biomarkers to predict their future state. We're getting there.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
you'd see rather dramatic increases in activity in brain regions such as the thalamus, the posterior insular cortex, the anterior cingulate cortex, the dorsal anterior cingulate cortex, and a number of other areas.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You would also see it in S1. You're right. And indeed, what we've learned through this, that there's no one single pain region in the brain. That's another mistake that was made along the way. We all thought we were going to find a brain region. Then we can knock it out, right? Just go cut it out. And it turns out that didn't work. It's not one brain region. that generates the experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It is a distributed network. It's all of these regions coming together and working in harmony. Doing what? Generating the experience of pain and then generating typically a response to that. Let me be very clear because there was a lot of controversy when we and others initially published our papers. We are not trying to take away the autonomy of the patient and the self-report.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I don't need an fMRI to see a patient and know if they have pain. I can just ask them. I can use self-report measures to get it. That's another part of the research. Where we're working to build these objective markers, this objectifying pain, is not to see what they're in now, but can it give us useful information? to predict treatment to a particular therapy?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Can we use it to predict their future state? Can we use it to predict their vulnerability to an injury or surgery? Those are things that just asking a patient right now probably not going to get there. I don't know if you want to go back to the brain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Roll with that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I want to build off it then.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That is basically your longer term harm alarm. That is saying, Peter, don't go back and do that again. Back in the cave people days, it would remind you maybe it's best to sit in the cave. and let the healing occur instead of going out and fighting the woolly mammoth or the saber-toothed tiger. Because if you fought the saber-toothed tiger when you're injured, you got eaten.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You didn't get to pass your genes along.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Wow, that's a great question. One, I don't know. Two, there was undoubtedly genetic variations that led to behaviors, led to actions that did not promote survival of the species. And nature takes care of that. Those people died out.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And when you go back through some of the lower animal species, what happens when one of those animals gets injured in the wild? I'm not an animal pain expert, but typically they're set off. They're ostracized. Those animals just die out. What do we do? We come together as a community and we help those people. We developed empathy for pain. I did some studies on that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And that has gotten hardwired into our brains to be able to recognize when people are in distress and pain and to reach out and help them. That was clearly beneficial to our species and conserved.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There's the formal definition of pain, which is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It's a mouthful. If you think of it as it's an unpleasant sensory and emotional experience, it's usually tied to something physically happening, but may not be.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Absolutely. And I got to tell you, hats off to half the population that are women and the women that do this. I can't imagine. I don't want to even go there.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There is interesting protective aspects during childbirth that doesn't take away necessarily the pain, but I think some of the estrogens, the estradiols has not only an analgesic effect, but I sometimes just swear, I don't seem to remember sometimes just how painful it was and yet they do it again.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I repeatedly tell Beth, I sometimes wonder why I was not a Darwin Award winner, if you've ever read the books. I remember the Darwin Awards fondly, yeah.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So we have these signals. I'm going to take these signals from the spinal cord, because where it gets really interesting... is when you take those A delta C fibers, you're in the spinal cord, and there's a lot of processing going on there that we'll come back to, and they head up to the brain, and then they synapse, connect in a large number of brain regions.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
One of the main one is the thalamus, which acts like grand central station in the brain. It's taking lots of sensory input from different sources, and it's sending it out to other areas. Some of those areas that we alluded to, the anterior cingulate cortex. Now, the anterior cingulate cortex, each of these brain regions has some functions associated with it.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The anterior cingulate cortex is associated with some of the emotional aspects of pain or the unpleasantness of it. For the neuroscientists out there, I'm grossly oversimplifying things. The anterior cingulate cortex is also a salience detector, meaning it is taking those incoming inputs and it's determining, is there something wrong here? Is there an error?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Because in essence, our brains are prediction machines. Everything that we're doing, we're forming an expected pattern of what we're going to sense and we're making adjustments. When I reach out for my cup, I know where it is in space, I pick it up. If instead of cold water in that, it's boiling hot water and I touch it, my brain is getting different signals than it was expecting.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That cingulate cortex as a salience detector is triggering and it's putting into action for me to withdraw. Other areas of the brain include the insular cortex, which lies on this little bit of the outer edge. It can be subdivided into multiple components, the posterior, mid, and anterior insula. Let's just say that the back part of it is taking direct information in from the body.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But then as you get more and more towards the front of the insula, it's integrating emotional and cognitive nuance to it. It is integrating in your emotional state and what you're thinking. Now, there's also connections with your amygdala, this deep, primitive region of the brain involved with both threat detection as well as reward.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think sometimes what's missing in that definition, one of the things I wish they had put in but never did, is that pain is the great motivator. Pain is one of the most primitive experiences going back to, if you will, single-cell organisms. It's either pain or reward. You're either being driven towards oxygen, food, sex, or you're trying to get away from danger.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it's connected into the circuit and then also has outlays into other areas that maybe we'll get to, like the hippocampus and the stress response and onward. All that to say is all these regions connected together generate that experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And at this point in time, I really haven't done more than Rene Descartes has in telling this story because first pass, the brain is still remaining a passive receptacle just taking these inputs. Where it gets interesting is we developed descending control systems that come down from the brain That converge in the spinal cord. And what they serve to do is turn down the signals that are heading up.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, in part, this was first described by Ron Melzack and Patrick Wall in, I think it was 1965, the gait control theory of pain. Brilliant guys. Never had the pleasure of meeting them, but they just did seminal work.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And this gate control theory of pain posits that, yes, you have afferent information coming in to the spinal cord, but the spinal cord is acting like a gate of opening and closing, turning up, turning down pain, and it is altered. by other fibers and systems from your brain. So let me give you an example to this. Let's introduce another nerve fiber type, A-beta.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
A-beta fibers are your touch fibers. When you touch or stroke your skin, those get activated. When you stand up and you stand on one leg, they're also responsible for position sense. They have a heavy coat of insulation around them and they are wicked fast. C-fiber is one meter a second. A-delta fiber is 10. A-beta fiber is 100 meters a second. Fast. That's why you can dance.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's why you can walk because you've got those fast reacting A-beta fibers. Now, let's go back to your thumb, Peter. You just hit your thumb with a hammer. Sharp jolt of pain goes to your brain. Got a little delay. Oh damn, this is really going to hurt. Hot burning flooding sensation comes over your thumb. What is the next thing that you do? Everybody does this a little differently.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Before or after swearing? There you go. A lot of people swear, so it's after swearing. You swear and then- Shake it. Shake. Okay. You're a shaker. Or a squeeze. Squeeze. Proximal to it. There you go. You squeeze, you shake it. Sometimes you run it underwater. What are you doing when you're squeezing it and shaking it?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, that's beautiful. And you're talking about longer term things which are all perfect. Because cold does those things, and also cold, by the way, reduces action potential velocities and firing in those A-delta C fibers. But what you're doing most of all when you rub it is you're activating A-beta fibers. you're actually not influencing much your A delta or C fibers, those nociceptive fibers.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You're not really impacting it there. That horse left the barn. That horse left the barn. You got horses still running out the barn. You can squeeze all you want for the time being and the horses are still heading out and hitting your spinal cord. But where things get interesting is the A beta fibers, those touch fibers,
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They're coming into a slightly different area of your spinal cord, and they're sending over projections into where those nociceptive fibers are in your spinal cord. And they have an inhibitory role. That's the take-home message. So the A-beta fibers are inhibiting the signals coming in from where you hit your thumb with a hammer and preventing them from going to your brain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's a beautiful example of neuromodulation. You're doing your own neuromodulation with that. And we're all hardwired to do that thing. And there's a medical device that takes advantage of that. You're familiar with the TENS unit? TENS is T-E-N-S, Transcutaneous Electrical Neural Stimulation.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Pain is so wonderful because it's so terrible. It keeps us alive. Without pain, when we have these genetic issues of congenital insensitivity to pain, we would have never lived as a species. So pain is an unpleasant sensory and emotional experience. To understand pain, whether you're a Martian or you're a human now, I think you have to look back in history.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, what it originally did, there's been modifications of it, is what you do with the TENS, I know you know this, is typically little black pads that you put over the area that hurts. You put an electrical stimulation through these pads. They're activating A-beta fibers. And so you do them over here and it's having a neuromodulatory effect back in the spinal cord. Pretty cool when it works.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I would just build on that, that I would say my job, our job as pain docs is to help reduce the pain and help them down a path of functional rehabilitation. So absent that second piece, I typically fail. I'm leading them down a road of functional rehabilitation, which involves physical, psychological, social, emotional health, all things you talked about beautifully in your book.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Somebody with, I think, more, you know, there's no susceptible musculoskeletal pain. I tend to think of somebody for whom TENS is more likely to work, something that has more of a classic nociceptive type of pain problem. Beyond that, Peter, it's a trial and error.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's part of the frustration in pain management and in healthcare in general is the lack of a precision approach and the very frustrating, laborious trial and error process until we get something that works. So we talked about the gait control. We talked about TENS.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You're right with that individual perception. variability, and pain. We haven't talked about the brain's role in the gait control, which we're going to get to, but just getting to your question, there's been some elegant studies. A guy named Kim, years ago, did a beautiful study where he applied a 48 degrees Celsius stimulus to 500 people. 48 degrees Celsius, I think it's 121 degrees Fahrenheit.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Somebody will look it up. And you apply it to the arm, the hand, and then ask, what's your pain score? And what he found was perfect distribution of people who said, nah, this ain't painful. Ain't nothing. That's like zero, one out of 10. Some were like, yeah, it's a little painful, two or three. And others were like, yeah, a little more moderate, four, five, six.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And you got all the way up to some people saying, oh my God. You're burning me. You're burning me. Take that off immediately. 10 out of 10. I do the same thing in a medical school demonstration. Can't call it an experiment because I'm not getting IRB. But when I teach the neuroscience class around pain, I bring in a circulating ice water bath.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so I'm going to evoke Rene Descartes, 17th century French philosopher, thought to be the father of modern philosophy. Incredible contributions brought Cartesian geometry to us, which led to calculus. And he had this dualistic model of pain. that he put forward.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And you want it to circulate because if you just stick your hand and leave it in still, you get a boundary. It's warmer.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So circulating ice water bath. And I asked them to dip their arm in for 15 seconds, pull it out, whisper in our research assistants here what their pain score was. We tabulate that all up. And at the end of the class, I show the medical students. And it looks just like that line I showed you, I mentioned to you before. You got some people in the class who say, I keep my hand in there all day.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And there was others who were like, oh my God, I couldn't even keep it in there at all. 10 out of 10. The whole point of that is to drive home one of the key messages in our discussion. The amount of stimulus or nociception may have little to nothing to do with your experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And why that is so important for healthcare professionals to understand is because for so long, we have projected our own experiences onto everybody else.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You're absolutely right. And maybe that's a good opportunity to build on that and introduce more of the brain. So we've talked about the functions of the brain, the cingulate cortex being some of the more emotional, the primary somatosensory cortex, the homunculus being more sensory, the insular cortex has an interoceptive state. It's like our internal awareness of our bodily state.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We talked about the amygdala. Now let's introduce also the prefrontal cortex. The prefrontal cortex, the big thinking part of our brain up here, both the ventral medial and the dorsal lateral, play a key role in our modulation, our cognitive control of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And these systems, the prefrontal cortex, the insular cortex, the cingulate cortex, all have those descending projections back down to the spinal cord. So we talked about the gait control theory of pain in the context of rubbing your finger out here, a peripheral neuromodulation. Where it really comes into play is when you introduce brain systems.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The brain and your emotions, your cognitions, your beliefs, your early history, And that influence on pain, that's where it gets really exciting. And that's sending descending pathways down. So I would argue, in part, that your experience of cold water in that moment may have been driven in large part by your mental state before you got in.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
To his credit, it was the first mechanistic foundation for pain because beforehand, pain was thought to be something mystical or religious. It was punishment of the gods. So he put this framework together that's often illustrated this famous picture of a little boy with his foot in the fire. And there's a little string from his foot going up into his brain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And maybe we'll talk more about the intersection of sleep and pain. Huge research in that space. Your state of anxiety, apprehension around this, all sorts of cognitive emotional aspects weigh into your experience of pain. And yes, there's also circadian rhythm aspects related to this from hour to hour fluctuations. But those individual differences are fascinating.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And that is also an area that our group and others, our lab and others are going into is recognizing that one pain score averaged over a week may not give us a lot of information that we need to take into account the within subject, within person daily variations over time and model that.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Yeah. That's what society values. That was my home life growing up. That's what my father expected. I come from a very working class. My father had 12 brothers and sisters fighting for whatever scraps of food. And he brought that into my world, our world as kids. And you just suck it up and deal with it. And my father had back pain later in life.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And he would never talk about it, would never ask my opinion. And when I offered my opinion, he would never follow it. Had bad consequences in the end. But we value that. That is just the way our society is. Is that a male thing exclusively? I think you need to get some women on the show and ask them. I think it crosses, actually. I do think there is a masculinity aspects of that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I think I could be wrong here. I think that that thing is also attractive for women. I think there's a certain attractiveness because that person may be more likely to be a good provider than somebody who is weak and sensitive. But we're getting a little out of my wheelhouse on that. But you're absolutely right.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
My fiance, we're now engaged, is a professor at Stanford, Beth Darnell. She's an ex-ultra marathon runner. And I've always admired the fact that she can sit there in front of a computer or work on something untold hours and not move. And she's just like, listen, I was really good with running with a pebble in my shoe, putting one foot after another and just working my way through it.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I similarly grew up in an environment where you learn to be tough and you learn to power through life's adversities.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
As with all things, it gets a little bit more nuanced. We talked about cold, for instance. It turns out that some of the sensitivities are modality specific.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it ends up in the pineal gland, which was thought to be uniquely a human area. And the idea is the fire pulls on the little string, opens up pores in the pineal gland, rings a bell, and the boy withdraws his foot. The idea is in this dualistic model, there is a complete separation between body and mind. The body is where pain is generated. The mind is where it's perceived.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Somebody who runs a paint lab. I've had everything done to me imaginable. I take heat really well. My son, Ian, takes heat really well. I've had thermal devices on me where I've been there and ended up with second-degree burns to find my 7 out of 10. I hate the cold. I hate it. I'm a wuss when it comes to the cold. So I live in California. I lived in Arizona.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think there are genetic aspects of this. So we have to be mindful modality specific. On top of it, these experimental protocols probably have little bearing on somebody's experience of chronic pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This is now where we move out of that Descartesian model. We appreciate the role of the brain and its modulatory capacity, its ability to turn the amplifier down. And so if you're thinking about a stereo amplifier, we talked about how some people to a certain stimulus might be a zero or one on the dial, some might be a 10.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But what we didn't talk about are people's capacity to now manage their pain, cope with their pain, their level of self-efficacy around their pain. Athletes learn how to manage their pain and suffering. Where they run into problems is when the sports are over. They're retired. That's when I see them. So there are many factors that predict how well somebody is going to do with chronic pain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They align with a lot of the stuff in your book. So the level of a person's self-efficacy plays a role. There is the presence or absence of whether they've got underlying depression, anger, anxiety, something called catastrophizing. Terrible word, very important concept, probably one of the most predictive of amplified pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yes. One of the biggest predictors of diabetic neuropathic pain is glucose control. So one of the first things we do if we have a person with diabetic neuropathy, which the diabetes, the high blood sugar, as you know much better than I, causes injury to those nociceptive fibers and also causes injury to the A-beta inhibitory fibers. That correlates with glucose control by way of example.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Diet plays a role because if you're eating things that are causing inflammation, we didn't talk about all of this stuff. that amplifies or winds up those peripheral nociceptors. We treated those as a static thing when they're not. They're dynamic. So in the face of inflammation, that causes something called peripheral sensitization.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You've turned up the amplifier on that nociceptor in the periphery. Sleep, huge topic.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We're both out of residency long enough, but we both pulled our old-nighters. How did you feel the next day?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But the mind is simply a passive receptacle receiving these signals. That model put forward in the 17th century stuck with us for hundreds and hundreds of years and I would argue is with us today. And it has influenced medical care. It has influenced policy. It's influenced everything in our society about the way we think about pain. And it's utterly, completely wrong.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's a haze, and you're just powering your way through it. And if you think about it, you're kind of feeling a little achy all over. Now, it's not that because of lack of sleep, something has changed in your muscles. I don't think there's good evidence for that. What has changed... is your set point in your brain and your spinal cord for the perception of pain. You feel like crap.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, imagine if you're doing that day after day after day and not getting sleep. That really messes up your central nervous system and that modulation around pain. What happens is it changes your set point and it impairs that prefrontal cortex and its ability to modulate pain. When you went through, Peter, your bad episode of back pain, did it impact your sleep?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You're human. That impact on sleep ultimately further amplified your pain. On top of it, how did you feel during that? And outside the pain, how was that affecting your overall life and your thoughts and your emotions? Total disaster.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So, yes, he got Cartesian geometry right. But he really, complete bollocks, screwed it up when it came to pain. This biomedical model, this dualistic model, was with us for hundreds and hundreds and hundreds of years. And it's only been in the last number of decades that we've appreciated the nuance of what pain really is.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. That's a terrible story. And I have to imagine one that has probably shaped you moving forward and had a big impact on your life and what you've been doing.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Well, I hope we can come back to that and talk about it more and the influence of all this other stuff that was probably contributing to your experience of pain and the bad stuff going on as a consequence of it. And it plays a role in everybody else's life out there. And I think there's some key messages there. What would you like to segue to?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
These medications are cyclooxygenase inhibitors. What they do is a couple of things. They reduce some of the inflammation. They're anti-inflammatories. So I was alluding very briefly that there are substances that can be released down in the periphery during injury that wind up that nociceptor and amplify it. Prostaglandins, histamines, cytokines, interleukins, all of that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This inflammatory soup that occurs after every single surgery, every single injury that we experience. You get this inflammatory soup, and it's classically mediated by swelling, redness, temperature increases, and aspirin and a COX-2 inhibitor NSAIDs do a nice job in reducing that inflammation. Now,
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This is where medical science, you're going to probably be much more informed than I am on this, but medical science has been slowly shifting in its view of this. We have historically thought, take these medications in an acute injury, it knocks down that inflammation, and all is well and good.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, some of the data was coming out in the orthopedic literature decades ago that people who were taking NSAIDs during total joint replacements were getting non-fusion of that joint to the bone. They were getting failures.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And instead of it being under this guise of this separate mind and body, we now appreciate it is this integrated biopsychosocial phenomenon. Meaning that, and I think this is one of the most important things that I'd like to drive across.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And then more recently, there's been some question as to whether knocking down the inflammation is a good thing after all, that maybe that inflammation is part of the healing process. And that by giving an NSAID aspirin, we're delaying the natural healing effect and causing more problems. So where's the truth? This is tough. One, I don't think we have the whole story yet on the NSAIDs.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Two, I'm a gray guy, meaning I don't live in black and white. And I'm also appreciated that every medical field has their own lens that they look at in the world.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I think we have to appreciate the complexity of the patient, meaning if it's perhaps something minor and they can get by without the NSAID and it's not going to change significantly their level of function, then maybe not taking it will improve healing. They can't get out of bed. They can't go to work.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
but a naperson helps them to do that thing so that they can engage with their family, with their friends, with work, well then, heck yes, take the NSAID if it's helping with that level of functional improvement.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
A little of both. But I think through chronic pain, we start to introduce all the longer-term negative consequences of this. Impact on blood pressure, your heart, impact on your kidneys with long-term NSAIDs, particularly if you're older. I remember, I think it was in your book, you took Vioxx. Yes. I loved Vioxx.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I stockpiled it. I wish I did. I called up all the drug reps I knew because they couldn't like give it out. And I'm like, can you just hook me up? So I ran out a stockpile of that for a long time and cut this if it's too tangential, but Every field looks at the problem through their own lens. Here, you had a drug that was causing heart attacks.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Stop using the 50 milligrams. Use the 25s. And you're right. Don't give it to insusceptible people.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We all do this. We look at the world through our own particular field. It's like with the latest blood pressure guidelines, the cardiologists want it really low, but it screws up the kidneys. And well, the cardiologists say, save the heart, screw the kidney. So great drug. Wish it was still around.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I'm going to introduce a term, we're going to get to a term called nociception, which are electrochemical injury signals that occur in the periphery, that what goes on in the body is And what goes on in the brain, the experience of pain, they may have nothing to do with each other or very little linkages. And we're going to hopefully unpack that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So NSAIDs nuance around taking the verdict.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Make sure.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Food in the stomach, fluids. If you're either older, you've got kidney issues, you've got GI issues, talk to your doc first. Don't just go into this stuff blindly.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I mean, the ERs see people with acetaminophen, Tylenol overdoses, and it's a cause of, well, you know this. Liver failure.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Minimally, more information. And I haven't, in full disclosure, I haven't read up on it a lot. I know it has some cyclooxygenase I impact. A lot of it is thought to be central. I haven't tracked it much beyond that. I saw some interesting side studies where it seems to have some impact in the brain around emotional modulation. And so there's a degree of emotional blunting on acetaminophen.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, whether it translates into a real world or if it's just an experimental manipulation, I don't know.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think you just said it, Peter. You said it beautifully. I use those in combination. to get the twofer, to get that synergy. The one plus one is not two, but three. So you can take Tylenol. Historically, we would say up to four grams a day. More recently, there's been some push to try to reduce that to two grams a day.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Clearly, if you've got liver dysfunction, if you are drinking large amounts of alcohol, less.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So hundreds and hundreds of years, we're basing it on Rene Descartes' dualistic model. We still see this in medical care right now. You're a surgeon. For many, many, many, many years when I talked with the surgeons, They were firmly of the opinion that the amount of pain that a patient had after surgery was related to how much the scalpel cut and how much tissue damage was done.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now let me ask you, does ibuprofen work better for you than naproxen?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The reason I ask is I find huge individual variability in responses to NSAIDs.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Naproxen works beautifully for me at 500 twice a day. Ibuprofen, not so good. At what dose? 800 three times a day. Wow. Yeah. With food and water.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I don't find it as effective in neuropathic pain. It might take a little bit of the edge off. Nociceptive pain typically is your go-to. You're kind of your nociceptive or... You're nociceptive inflammatory pain, the kind of pain you'd see in a joint. Those are your typical go-to forms of back pain, particularly in acute situations, but also somewhat in chronic.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I get a lot of patients that say, yeah, that didn't do it for me. But if you inquire and ask questions, you find maybe it knocked it off a little. Because in our game, we're trying to knock off pieces and pieces and pieces of their pain experience. The issues with the different responses are very individually based.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I think in part, it has to do with a little bit of what we call pharmacokinetics or where the drug is getting. And different NSAIDs can permeate different tissues at different rates.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Obviously, don't take them together, but your take-home message is spot on.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I just said a conserver, listen, don't do more than like a drink a day. Is that the right amount? I don't know. But if I tell them one drink a day, they'll go do two. They're probably still okay with that. And then I am looking in their chart just to make sure they're not drinking four or eight and there's liver issues. What do you do?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I think it's only more in the last 20 or so years I'm seeing surgeons really embracing this model that what people bring to the operating room table directly influences how much pain they have. Their early life experiences, all this stuff. And we'll talk about that.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Beautiful case example, by the way, for yourself of how we would use those. Baclofen is one of the safest to use. It is not habit forming like the Soma's. and others that can be like a barbiturate, can act, and people can get highly psychologically dependent on them.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The flexorils have a tricyclic antidepressant property about them that may sometimes be helpful for people in various mixed pain states, but also can cause sedation. The baclofen seems to be pretty benign. We don't typically use muscle relaxants for long-term chronic conditions. The data hasn't borne out.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Oh, I'm comfortable with a person being on Baclofen all their life. It's just, forgive me if I'm preaching to the choir here. Everything I'm doing is taken in the context of the person in front of me and the cost and benefit of the treatments I'm providing them. Meaning there are costs with Baclofen. I don't mean monetary cost. It can cost sedation.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think it's individual, and obviously it is dose-dependent. The higher dose is more sedation. We can use baclofen intrathecally. We put in intrathecal pumps for baclofen. This is a beautiful, life-saving, minimal surgery that we do for people with a spinal cord injury and tractable spasticity, because to get the spasms under control with oral doses, you just can't get there.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So we thread a little catheter into the CSF and we deliver baclofen that way. Now, it, again, is a clean, relatively safe medication, but I'm always evaluating long-term, is this person getting benefit from this? Should we be talking about dialing it back and trying to wean? And if they're not getting benefit, then why should they stay on the medication?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I know you do the same types of things in your practice. We use it. We can use it in acute, subacute. We'll use it in some chronic conditions as a trial. What's a trial? Month, two months. And then we monitor data on every single person.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, up to 80 milligrams, I believe, is the upper end. I don't usually get there.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The beauty of Neurontin or Gabapentin and its cousin Pregabalin, which was introduced immediately after Gabapentin's patent ran out. Conveniently. Very conveniently. Both have the same mechanism of action. They work on the alpha-2-delta subunit of a calcium channel in the spinal cord, in the brain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's a little too jargon-y and technical, but think of them as agents that turn down the signals that are in the spinal cord being processed and in the brain. So they're really not impacting your nerve out here or in your leg. They can be very effective. The beauty of these two drugs is there's no lethal dose.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The only way they could kill the rats when they were studying it was to drown them in it. I used to say, or hit them over the head with the tablets. And I would tell a patient somewhat jokingly, the only way you can be hurt taking this drug is if you're struck by a truck that's carrying it. It's a little bit more nuanced than that because there are side effects.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You can fall asleep driving. I tell people, don't operate heavy machinery. Don't go dune buggy riding. Don't blah, blah, blah. There is, in elderly patients in particular, I warn them about falls because you can get a little unstable.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, it's more I see water retention. I see a little peripheral edema in both.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I don't know the data on the sleep architecture, and that would be something I'd be putting out to you or some of the sleep experts. I have taken it after surgery. I find that it makes me sedated. I don't find the quality of the sleep. Okay.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's it. That's it. It could just simply be my experience. The truth is, I do tend to, when I dose it, I'll dose lower in the day. and then I'll wallop a little harder at night for the very reason. So let's imagine gabapentin maybe in the day 300, 300, 600 at night. And I'm trying to titrate that so that, one, it helps them sleep.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Because you brought up an incredibly important point, which is during the day, we've got all these modulatory things we can do around our pain. Distraction, for instance. Other coping strategies at night, you're just trying to get into this relaxed state. And that is the worst time for somebody with chronic pain. And so the gabapentin and sometimes other agents can help with that.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So yeah, I do use it to help people sleep. No lethal dose. Maxes out at around 900 to 1,000 milligrams at a dose because it's taken up by an active transport system in the small intestine. Once you take more than about 1,000 milligrams, the rest of it's just passed out your backside. Pre-gabalin is different.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It has what's called a linear kinetic profile, simply meaning the more you take, the more that gets in your system. So the only times I will typically switch somebody from a gabapentin if they're getting benefit is when they've maxed out the dose. They're getting benefit, but there's no point in giving them more. I'll switch to pre-gabalin where I can drive more into their system.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I'm using these for the most recalcitrant pain in general. So that's an important point. While I can speak to perioperative pain, acute pain, subacute pain, and chronic pain, Stanford, we tend to see, we're a tertiary referral center. I tend to see, we see people after they've seen everybody else.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There's various definitions. Some like to put a time frame on it, which I think many of us believe is a little artificial. It's not three months or six months. It is pain that persists beyond the expected time of tissue healing. So, it is nuanced. It's context-specific, meaning...
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
If you have an inguinal hernia repair or a prostatectomy, which should heal up pretty quickly and your pain should go away pretty quickly, but if you've got pain after a couple, few months, that's starting to get to that point where I'm a little worried something's going on from a chronic pain. But if you had a total knee replacement...
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Had no influence on that model, which I think has had tragic consequences in the care of people, particularly with chronic pain. particularly women with chronic pain who have felt stigmatized, invalidated, because absent something that's obviously wrong out in the body of the periphery, they were just labeled as being histrionic housewives or being told it's all in their head.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
that is a massive, massive surgery and you're going to have pain for quite some time. So I wouldn't call chronicity for a total knee. Totally makes sense. Context specific. This gets into also some of the whole issue around opioid prescribing and these rigid timeframes for surgery and what have you, but persistence beyond the time of expected tissue healing.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
These are credibly effective agents, not necessarily for their antidepressive properties. They frequently work through modulating a couple neurotransmitters, serotonin and norepinephrine, and to varying extent.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We find that the classic, what we refer to as SSRIs, the selective serotonin reuptake inhibitors, haven't been as effective for pain as the older dirty drugs of the tricyclic antidepressants. We call them dirty, which simply means they act at multiple receptors. They hit multiple systems.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So these tricyclics hit the serotonin and norepinephrine systems, and then they also happen to be pretty potent sodium channel blockers. Why the sodium channel blocking property is important is when we talked earlier about the peripheral nerves, one of the main drivers of an action potential is activity around the sodium channels. You block the sodium channels, the action potential stops.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Do you remember how much you gave me? Of? How much sodium?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, that's the thing. We all get comfortable with our top two or three of any class. My go-to is desipramine, nortriptyline, and amitriptyline. They're broken up into different categories based on mainly side effect profiles. After nortriptyline, what was it? Amitriptyline or alevin.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So Elavil's an older tricyclic that has a lot of histamine release, a lot of sedating properties. I would never give that to an older guy with a big prostate because he couldn't pee and he'll be very angry with me. I will never give that to a young woman who's looking to watch her weight because she's going to get the munchies and she's going to put on 10 or 20 pounds and she's going to hate me.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Have I had that happen? Yes. And I'm still embarrassed to this day.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I've learned my lessons. I haven't run that experiment. That's a great idea. But I typically use the amitriptyline when I need some sedating help at night for sleep and pain because of dual action. I like the dicipramine because it has less of that sedating property. And I'll tend to go to that and the nortriptyline. And you can titrate blood levels, for instance, like the nortriptyline.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And those drugs, so where do they work? They work in the brain. They work in the brainstem. One of the classic areas down deep in the brainstem is a rostral ventral medullary region where descending pathways are coming down. And some of the key neurotransmitters there are serotonin and norepinephrine. So we're not necessarily using these drugs for their mood-changing properties.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We're using them because they hit the same systems as they do in pain. And that's the beauty of them. And that's some of the messaging we have to give patients when we've prescribed them an antidepressant is like, okay, Mrs. Jones, Mr. Smith, we're not doing this.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
These are great, great, great pain drugs, but they were never FDA approved. Why were they not FDA approved? Because they're off patent. There's no money to be made.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Not just women, but also some men as well. And so it's only with that evolution of our perception or our model into a biopsychosocial model that that's gotten much better.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. It is a very nuanced question. I think a little preamble first. I don't take money from either the opioid companies. I don't take money from the litigation that's ongoing because there are tens and tens of billions of dollars at play right now. I don't take money. End of. I am not pro-opioid. I am not anti-opioid. I am pro-patient. I view them as a tool.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I view them as a tool much like the other medications, interventions, mind-body, physical rehabilitative complementary tools that we use. They have a particular place. I have a personal deep place. appreciation for the destruction that these agents can cause. I come from a family very deep in addiction, very deep. I've lost close family members to opioid overdose.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Let's talk about, is there a pain receptor? So let's break it down into the foundational stuff. So we have these things called nociceptors. Complicated name. It's basically a transducer, which is another technical name. Now, you're engineering background, so you all know that a transducer is simply a device that converts one form of energy into another form of energy.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I've lost close family members to alcoholism. I am personally petrified of these drugs. And I have gone through surgeries that the surgeon said, you can't get through this without an opioid. And I'm like, I'll be fine. Because my approach is avoidance. With that said, I have learned a long time ago not to project my personal experiences onto my patients.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That had to come through age, wisdom, whatever. It is true. Prescription opioids were over-prescribed. They were over-marketed. They were bad actors doing bad things. But it's not that simple a story. I sometimes get frustrated because I feel like you can make really simple sound bites out of this complex societal issue when it was a perfect storm that hit.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yes, you had a letter to the editor of New England Journal saying that nobody got addicted, like 38 patients or some nonsense, and Purdue and others ran with this, and I get that, and they did bad things. You also have to put things in the context of what was going on in society. There was growing awareness of pain, as there should be. There was growing pressures to do something about it.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
People have brought up the pain as the fifth vital sign as an example. People have different opinions about that. Did it have bad consequences? Yes. Did it have good consequences? Hell yes. Run the counterfactual. Do you want to go back to a time when we're not asking patients after surgery their pain? Do you want your mother, your daughter back in that time? And I think the answer is clearly no.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But also there was other pressures. And Peter, you witnessed those firsthand. What was going on back in the 90s and the 2000s? After surgery, there was this massive push to get people out of the hospital and put them in their home. we were replacing care in a hospital with care in the home. In the hospital, we had time to see their trajectory.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We could titrate their opioids or whatever, get them tuned up, dialed in, and then send them home. Now, Surgery, overnight, you're home, let's give you a bucket of whatever. And the reason for that was surgeons and docs don't like getting called at 3 a.m. for pain control. So pressure to put people out in the home environment. On top of it, docs get lousy training for pain. What is the average?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Seven hours, I think, in medical school. That's, by the way, 40 hours of pain. So great if you've got a dog. Not so great for... So you've got this pressure. And by the way, not only on top of that, but now you've got the introduction of patient satisfaction scores. I have to imagine in your private practice, you don't have to measure Press Ganey and patient satisfaction scores.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But in hospitals, everybody does. Or at least they did. I think they're coming to their senses. And so one way of addressing the satisfaction, give more opioids. And there's more. There's many, many, many pressures that came to bear that helped create this problem of which there were bad actors out there.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I have a slide, yeah, on the opioid crisis. I call it the perfect storm. You're absolutely right. And in the end, and here I'm going to be a little bit reductive when it comes to the docs roles in this. I'm going to borrow from my friend, Professor Keith Humphreys. There are three kinds of physicians out there. There are the majority of the physicians doing the right thing for the right reasons.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There are the next group, which is a much smaller group, physicians doing the wrong thing for the right reasons. And at the very top of that pyramid, a little group, you got physicians doing the wrong thing for the wrong reasons. Those people at the top take away their license, put them in jail.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But you had a group of people here in the middle that were doing the wrong thing for the right reasons, that they either didn't have the right education, they thought they were helping people. Did they contribute to the problem? Yes. Have they gotten educated? Yes. I didn't answer your question, though.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This microphone is converting sound energy into electrical energy. The speakers convert electrical energy back into sound energy. We have these nociceptors that lie in our skin, our soft tissues, our deep tissues, our viscera, and they're specialized. And they convert different forms of energy into electrochemical impulses. They take pressure. They take heat, cold.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Let me now circle back, and I hope you'll forgive that little bit of soliloquy on my perspective of that 20 years. I don't use opioids as a first-line agent ever. Almost never. End of life. Cancer. But usually by then, they've tried other things before they're getting to us. I will use end-of-life cancer pain. I'll use opioids liberally as needed.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Frequently, we have an acute pain service in the hospital that sees about 30 to 50 patients a day. Based on what?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Most frequently when the outcome is not simple. So when the surgeon needs some help, when the internal medicine doc needs help, and it's beyond their comfort.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. These days, there's a lot of movement towards these ARAS protocols and enhanced recovery after surgery. And so fortunately, the field of medicine is moving more and more towards a team-based healthcare model where Surgeons, pain docs, anesthesiologists, nursing, rehab are all working in a collaborative manner.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They're putting together protocols to what is the best optimal approach to prehab a patient before surgery, move them through the intraoperative and then perioperative period. And it's gotten better and better and better. Can we still improve it? Yes. But the acute pain service does get involved, particularly, as you alluded, when we put in peripheral nerve catheters or epidural catheters.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And this is where we're running that local anesthetic, the numbing medication that stops the nerve impulses to provide pain relief after surgery. And so, yes, we do get deeply, deeply involved in that acute surgical pain space. And then also with internal medicine docs when patients are admitted into the hospital for whatever cause.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Right. You are right. And if a patient is listening to this, a person is listening and they have the ability, they have the wherewithal to go to their doc, their surgeon, and ask, what will pain management be like? Is there an opportunity to interface with an acute pain service, particularly if
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They take chemical changes in the form of pH that can occur during infection. They convert those into action potentials that are then transmitted up nerves. These are little electrical impulses transmitting up generally two different nerve fiber types. These two different nerve fiber types, one is called a C-fiber, which is thinned. thin and slow. It's really pokey.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
if they're taking opioids now for a chronic pain problem, or even if they're not taking opioids for a chronic pain problem. So we will see them in our clinic before surgery. We will put together a presurgical plan for them, which will often include a regional anesthetic approach, meaning those nerve blocks or the catheters. We sometimes involve intravenous ketamine to augment.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We will put together the whole plan, communicate with the anesthesiologist, make sure there's a good handoff after surgery. And then we will follow them afterwards. And then we will typically follow them outside the hospital and help the surgeon out with the medication management and the pain management.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
All of this is not just solely to reduce pain, but to put that person in an optimal state for rehab.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Everywhere.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Fentanyl, morphine, Dilaudid, yes. The PCA is a very common tool. And one, it puts pain control in the hands of the patient. Two, studies have been shown that PCA-delivered medication, opioids, they end up taking less than if it's nursing-delivered.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I wouldn't say necessarily because I think there are some surgeries that are going to clearly require prescribing an opioid after surgery. Remember, the name of the game is get people out of the hospital and have the care take place in their home. And people are going to need some degree of pain management and analgesics. And those analgesics can be Tylenol NSAIDs.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
If it's more than mild, moderate pain, it may involve an opioid.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
What we have learned is that there are vulnerabilities that people bring to an injury or surgery and being placed on opioids that set them up for more likelihood of persistent opioid use. And we've characterized, we and others through research studies, have characterized many of these factors. So some of these factors include preoperative depression and anxiety, higher levels of catastrophizing,
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Early adverse child events, so a history of PTSD, history of physical, sexual, psychological trauma, all of these set someone up to have a higher likelihood of persistent pain and persistent opioid use. Now, you will note all these things I said, most of these things I said, people would normally put under the psychological umbrella.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The key message that I want to give, I think everyone's getting this, is when we talk about psychology and psychological factors, we're talking about neurosciences. We're talking about the brain. And we're talking about specific brain systems, regions, networks. So we did a study several years ago. This was led by Jennifer Ha. Ian Carroll was a key player, leader on this.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And we found that higher depression scores preoperatively predicted much more likelihood of persistent opioid use after surgery. And how are you screening for this? What tests are you using? Back then, we used something called the Beck Depression Inventory, which... Standard instrument, we don't use that anymore. There's more modern tools.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I thought what was cool about this, we did a factor analysis on the original paper, and you can break the BEC down into different components of depression, anhedonia, cognitive, blah, blah, blah. What we found is there was a particular factor. that drove almost entirely that prediction of depression, self-loathing. It was feeling like really bad about yourself.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I don't know if I'm getting ahead if you wanted to go more into that, but you got this pokey, slow C-fiber that transmits at about one meter a second. And the frame of reference, if it helps, is think about your thumb is about a meter from your brain. So an impulse on a C-fiber from your thumb to a brain takes about a second to two seconds to get there. The other nerve fiber type
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Conceptually, your argument holds. But now I'm going to come back to a lot of the things that you write about. which is the danger of drawing inferences from small population studies and generalizing that to the rest of the world.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's exactly it. Unfortunately, there's not much will to do that in society.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I was on the Institute of Medicine panel, now the National Academy panel, and we did a report called Relieving Pain in America. And I remember sitting around back in 2010, And we were talking about the state of pain in the country and where we needed to go identify a perfect vision and also identify what are the biggest research questions to ask and answer.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I remember a really vigorous discussion here. And the one that I put forward and others put forward is we need to better understand what is the long-term effectiveness and safety of prescribing opioids to people with chronic pain. meaning we need to figure out for whom opioids work.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Today, we still don't have an answer to that question, and there's very little will to do it because the whole message in the scientific community is basically find non-opioid choices. So there's not a lot of interest in funding the studies to figure out for whom it works. There is a lot of active interest still, mainly through data-driven studies, to find out who's at risk.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But that type of study that you're talking about and others that are of longer term and bigger consequences. I just don't know when they're going to get done, who's going to fund those.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's called an A-delta fiber. It's got some nice insulation around it. It transmits 10 times faster. So it takes a little under a tenth of a second to get your thumb to your brain. And to give a real-world sense of the difference in C-fibers and A-delta fibers...
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Oh, all the time. Yeah. I mean, I think he was ahead of the curve. Now, whether it completely eliminates any likelihood of opioids after surgery, that's a little too strong a statement. Look, it just reduces the requirement, right? I strongly believe that he was practicing good medicine and he was doing it ahead of his time.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, the idea of using a combination of lidocaine and marcaine and epi, as you well know, is lidocaine short-acting. So it's going to work pretty darn quick. And so you can get going with your surgery while the marcaine, the bupivacaine is kicking in. The epi is going to not only provide hemostate, it's going to reduce bleeding at the site, but it keeps the local contained.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There is something there there. And I think I haven't asked surgeons these days. And my sense is that's becoming more and more common practice, that there's a greater appreciation of the role of this concept of preemptive, preventative analgesia, anesthesia. I think it provides some benefit.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
There was a big hoopla on this like 20 years ago when everybody thought we were going to find a way just to basically eliminate post-operative pain through these methods. Presumably didn't pan out. It just didn't pan out.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Absolutely. Getting back to your question, I think we're at an interesting crux in research and clinical care where We're gathering more and more high-quality data to better understand these vulnerabilities.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I think we're going to be moving to the point of putting these into clinical decision support tools that can inform the docs and help them to assess a risk of a patient so that you can have an informed conversation with someone. Like you are at likelihood of having persistent opioid use because of what you bring.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I guess it a little bit is about their expectations. The challenge is when the ones who've had multiple surgeries that have been on opioids, they're expecting opioids, a lot of it's expectations. I think the more naive person, those go a little smoother. If you are professional, explain to them, but also allow them to make their own choices. Don't say, we're not going to give this to you.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But here you are in an increased risk. And that's always the discussion I have with patients, whether in the acute space or particularly in the chronic space.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Think back to the last time you stepped on a tack in the carpet, you hit your thumb with a hammer, you twisted your ankle coming off a curb. What happened? Think back to that experience. You get this sharp jolt of pain that goes right to your brain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Some people get better. Some people don't get better. I cannot yet predict who is going to respond and who's not going to respond. Is it a part of the work that your department does? Yeah. We actually have Dr. Jeanne T. Kong does the acupuncture. She's a pain doc. She does acupuncture.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And my view of acupuncture as a treatment, as a modality, is if you can afford the wallet biopsy and it doesn't cause you problems, then give it a try.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They do more so now on Medicare. And I think that the rules that went into place recently helped with that for older patients. I don't honestly know if it's translated down to the commercial carriers.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Historically been hard to get that
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. I've had some successes in back pain, musculoskeletal pain, migraines, headaches, oddly. And it's highly variable. I studied this. I had a really large program project grant to look at cortical mechanisms of this and predictors. We're putting in a paper now, which is a prediction model of real acupuncture versus placebo acupuncture.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, that's one option. And it turns out that many of these acupuncture points overlie peripheral nerves. And so when you twiddle the needle or apply electroacupuncture, are you doing a peripheral nerve stimulation? I don't know. But this is a Stridinger needle that looks for all intents and purposes like an acupuncture needle. It causes a little pinprick, but it doesn't actually do acupuncture.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it's been shown to be a good placebo. What do I know about the mechanisms? Again, don't fully understand. I know that there is increases in peripheral adenosine that is released with acupuncture that has an analgesic effect at the primary nociceptor. I know that cortically in the brain, there are brain systems that are modulated with acupuncture. But how could I know exactly how it works?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Those are your A-delta fibers at 10 meters a second, rapidly getting up to your brain, rapidly putting into play systems to protect yourself from harm. You withdraw. You have a reflex that's occurring in your spinal cord. You're not even consciously aware of it. Your brain is setting into play escape mechanisms. The pain that you experience is sharp. It's well localized.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And we still don't have good ways of predicting who's going to respond and who's not going to respond. But that's rather common amongst all of our pain treatments. You know, again, pretty safe. Absent some risk of infection, make sure that the facility you're getting at practices good hygienic approaches.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think you'll want to get a true acupuncture specialist on to dry that.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
If you're using the term dry needling from an intramuscular standpoint, I don't know if that's where you're going.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, it's an acupuncture point. It is a Chinese medicine list of acupuncture points. I'm way out of my wheelhouse here, folks. When I think of dry needling, I tend to think of that in the context of trigger point injections, which we do, physicians do. And that we're taking typically like a 30 or 27 gauge needle. We're putting it intramuscularly into a trigger point muscle.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's where you get those knotty muscles. Yep. And you can do dry needling. And what that does is it causes relaxation of the muscle. Acupuncture is really quite different from that.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Very nuanced. This is another one where I'm liable to get some hate mail on either side of this. Here's what I'll tell you. One, the verdict is still way the heck out there. You look at well-controlled, randomized trials. There's very few of them, by the way, but some in neuropathic pain that show analgesic benefit over a short period of time with cannabis. You look at population-level studies.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Australia did one. They did not show benefit with cannabis. We collect data. One of my other areas of both research, but also clinical care is I built a learning health system that captures high quality data on every patient that comes in. And so we deeply characterize or phenotype them. And we looked at people coming in on cannabis, not on cannabis.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Bottom line, people coming in on cannabis into Stanford are worse off and they stay worse off. Now, there's all these limitations to observational studies, no matter how well you conduct them. Let me distill it down to some talking points. There's a huge number of cannabinoid receptors in the human brain that are playing a role in analgesia.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So I'm absolutely convinced that cannabinoids are playing a role in pain relief. One. Two, the forms of cannabis that we take are dirty, meaning we don't know the dose. We don't know the ratios. They've not been well studied and they've not been studied in different groups.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
A major part of that is because it's a schedule one drug, which means that the DEA says basically high abuse potential and no medical benefit. And it takes basically an act of Congress to study cannabis. I don't prescribe it at Stanford. I don't screen people for it at Stanford. If I did and if we kicked them all out, I wouldn't have anybody in the clinic. I mean, we're in Northern California.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You can study it with federal dollars. NIDA will support funding of cannabis. The regulatory controls you have to go through are crazy.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You know exactly where you stepped on that tack. Then about a second, two seconds later, you get this hot burning flooding sensation come over your thumb with you hit it with a hammer. And you think to yourself, oh, damn, this is really going to hurt. And it gets hot. It gets burning. Those are your C-fibers, unmyelinated, slow, getting up to your brain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We used to make jokes. UCSF did some nice cannabis research. And the word on the street was that they would deliver the cannabis... doobies in a Brinks armored truck with guys carrying M16s. Now, I think it's gotten better, but it's just been challenging to study this. I'm firmly of the opinion, here's where I'm going to upset people.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I firmly believe we should make it a Schedule II or Schedule III drug.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Yeah. What was historically a garbage bag definition. Fibromyalgia is a condition of widespread bodily pain that impacts people above and below the waist, the diaphragm. It's associated with early morning stiffness, fatigue, mental fog, often some GI problems.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It was historically, based on American College rheumatology definitions, based on tender points in 11 out of 18 places, but that's been replaced.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
by now criteria which involves multiple body sites affected and a symptom severity score the key thing when the audience hears well first of all it's fibromyalgia syndrome and whenever the audience hears syndrome what they should translate that to the definition of a syndrome is a constellation of signs and symptoms that define a disease but we don't understand the mechanism
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So, fibromyalgia is a syndrome. We do not understand its mechanisms. We know that historically, it tended to affect women more than men, about 80%-ish or so women. With the newer definition, we're picking up a lot more men. The cognitive aspects of it are really a problem. It's also associated, as I alluded to, with sleep disturbances.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They get this weird, what we call alpha wave intrusion into their EEG, which means alpha waves are typically in light awakefulness. So when you're supposed to be in deep sleep or REM sleep, your brain is in kind of a light alert state instead. And so they're not getting a restful sleep. This is a syndrome that's caused untold problems, particularly for women.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I should know how many millions there, Pete. I should know how many millions and I don't. I can tell you just to give a frame of reference. Chronic pain, we think there's 50 to 100 million Americans with chronic pain. That's a huge range and it depends on the way you ask the question. If you ask it more stringently, it's 50 million. If you ask it more liberally, it's 100 million.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We know that there are about 8% of the population or a little over 20 some odd million with something called high impact chronic pain. This is a big one and this is where I spend a lot of my research and policy work on. These are the people that have substantial restrictions to their pain in activities of daily living. These are the really challenging people.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Of that 50 to 100 million, the most common chronic pain is low back pain at about 28%, neck pain 16%, headaches around 16%. Societal burden of chronic pain is terrifying. It's astounding. We spend over half a trillion dollars a year and chronic pain. And the reason why, in part, it's not more appreciated is because we have parceled it out. We've broken it into different categories.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And what you also notice for the first time is you don't like this. This has an unpleasant quality to it that you didn't get as much with that A-delta sharp pain, but you're getting with those C-fibers. That's really clear.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
With heart disease, we lump it into heart disease, cardiovascular disease, even though it's all these different subcomponents. With pain, instead, we categorize it as it's either back pain, it's musculoskeletal pain, it's migraines, it's abdominal pain, and it gets diluted out But when you put it all together, you're dealing with a half a trillion dollars.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's more than diabetes, heart disease, and cancer combined. Fibromyalgia, again, I'm escaping the prevalence. Many millions of people. Huge societal burden. It is... Historically, a disease of histrionic housewives is how they were mislabeled, tragically. And we're having now a greater appreciation for what it is, what's affected.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
What we have learned is that there are brain systems that are clearly abnormal in the processing of pain in people with fibromyalgia. We find that for the same pressure stimulus, if you apply something like four kilograms per square centimeter, healthy people will give a range of reporting in a certain range. People with fibromyalgia, much, much higher.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Here's another, I think this is an interesting pain concept to introduce and talk about it. There's something called conditioned pain modulation. In the animal world, we call it diffuse noxious inhibitory controller, DENIC. CPM. Think back to when you were a kid. Your arm hurt. You walk up to your buddy. You say, hey, man. And he's like, how you doing?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's like, well, my arm's kind of hurting a lot. And what would he do? Hit you? He would hit you, of course. He'd hit you in your other arm. He'd stomp on your foot. And you're like, why the hell did you do that?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This is what little boys do. I was guilty of a lot of that. But then you'd say to your buddy, like, don't you feel better? And the truth is you did. Because pain in another area reduces the primary pain site. It's called conditioned pain modulation. We're all wired. It is
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
a network predominantly, we think, in the brainstem involving some of this periaqueductal gray rostral ventral medullary regions. Labar's first described this in the mid-70s in animals. So we all do it. We all have it. It's this endogenous tonic inhibitory tone that you can activate when you cause pain in another site, unless you have fibromyalgia.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
If you have fibromyalgia, particularly if you're a woman with fibromyalgia, you have impaired CPM. You don't inhibit
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. We used to think that there was a high preponderance of anxiety and depression with fibromyalgia. And I think the current data... doesn't support that there's any higher prevalence than particularly any other pain conditions. I think you tend to see more of the anxiety, depression, broadly speaking, in things like low back pain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think what you see more of in fibromyalgia is fatigue, unrelenting fibro fog is what they call it, and then the sleep disturbances.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yes and no. What do I mean? Well, one, we don't know exactly the mechanisms. There's different prevailing thoughts. One thought, again, is it's a disruption in your central brain processing of pain through reasons unknown. There are some that believe it is a disease, a condition of small fiber neuropathy, because you can do punch biopsies, little, little skin biopsies here.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And what they find in some subsets of people with fibromyalgia is those C fibers... That there is alterations, abnormalities of the C fibers in the skin. And that is synonymous with a small fiber neuropathy that neurologists typically see.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's the thing. Is this infectious? What do people think is going on? So fibromyalgia is frequently preceded by some event, something traumatic. That traumatic can be physical, motor vehicle accident, but it could also be some emotional or sexual abuse. It can be an infection. We frequently also hear that story. So there is some insult that people will frequently identify.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Getting back to your question on managing this, we frequently use the same medications that we've described before, but we rely on more of those brain modulatory drugs. Another one's like duloxetine, which is in the class of antidepressants, but it's a little cleaner, fewer side effects. It's a serotonin norepinephrine reuptake inhibitor. This is actually a drug that got FDA approval for pain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so we go to this a lot. One of the drugs that I have studied with Jared Younger, who's now at UAB, is a drug called low-dose naltrexone. This is a fascinating drug. It's got like this underground reputation out there. It's all over the forums. The reason for it is because it's been around for decades and off patent, there is zero money for any pharmaceutical company for it. What is naltrexone?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's exactly it. And it is synapse, and there are synapses in the ventral or anterior, the front portion of your spinal cord, which is, as you know, your motor part of that spinal cord. They're making synapses, and it's causing a classic withdrawal effect.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Naltrexone, when given at 50 milligrams, is used to block opioid receptors. It's an opioid blocker. And so we use this in the treatment of opioid and alcohol addiction because it blocks the rewarding experiences of alcohol or opioids. And so it's used as a treatment for addiction. 50 milligrams.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
At four and a half milligrams, one-tenth of the dose, it has been shown to block Toll-like-4 receptor on the microglia. Now, I just introduced this really technical concept, so allow me to briefly explain. The microglia are these cells that hang around nerves but are not neurons.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And when I was in medical school, a few years, several years before you, what I was taught was these microglia were like the warm fuzzy blanket that propped up the nerves. I don't know what you were taught, but they provided structural support to the nerves. What I learned is that was only part of the story, that they're key neuroimmune modulators.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so what I mean by that is, in times of stress, injury, fever, these microglia get activated. They release all sorts of inflammatory mediators, chemicals, that sensitize the central nerves responsible for pain perception, pain transmission, pain perception. So you give low-dose naltrexone, it blocks that neuroinflammatory soup. And in some patients, Peter, this drug's been magical. Magical.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I give it in four and a half milligrams.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
All right, here's my story. Linda Watkins and Mark Hutchinson did some of the early work in the animal studies on this and showed this microglial effect. And they did it at a certain dose. And so what we did is we did a milligram per kilogram conversion to 70 milligram.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
70 kilo person. Thank you. And we get four and a half. And so when people ask me that, I'm like, wow, it does make us sound pretty smart, doesn't it? There's no difference between four and a half and five.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Complex regional pain syndrome, very tragic pain condition that is a neuropathic pain condition we see a fair amount of. I've got a clinical trial I'm just wrapping up on that using low-dose naltrexone funded by the RSDSA Association. Another is actually multiple sclerosis they've used it in, and they found some reduction in reoccurrences of MS. I think they did that at UCSF or UCLA.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But it's in these weird neurodegenerative-type conditions where they're seeing some help. Now, I've had some wacky, really wacky patient responses. I can share one. He is dysarthric. He can't speak. He's got weakness. He has hemibody pain, burning pain. This is that central pain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So he comes to me several years later, can barely speak at all.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
No, no, no, no. He has a speech therapist. It's not getting any better. He's a couple of years out. Stroke is stabilized. Okay, so it's this burning pain. Burning pain. On half his body. Half his body. I trial him on four and a half milligrams of LDN. He goes away. He comes back a couple months later. Pain has improved.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But not only that, he's now speaking and throwing a few words together for the first time since his stroke. I'm like, what the hell? I bump up his dose. You cannot hurt yourself on this drug. I know you know this. So I go to nine. Why not 10? Well, because it's easy to take two capsules. He comes back a few months later. He's now talking in sentences. I said, are you sure?
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
This isn't due to your speech therapist. And they swear up and down. Absolutely not. I go up to 13 and a half, and now he's having conversations. And how's his pain? Massively better on this. Really remarkable effect. The only way I can explain these things is, you know, in a stroke, you've got dead tissue, you've got live tissue, you've got these intermediate zones. And
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, they would still feel pain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Somehow, with reducing maybe inflammation, you end up with more functional brain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
drug is the only side effects I see. 20, 30% of people get vivid dreams. They get technicolor dreams, not bad dreams, not nightmares. Their dreams just take on a more colorful nature. Every once in a while, I'll see somebody who they say it activates them. We tell them to take it two hours before bedtime. And if it activates them a little bit, take it in the morning instead.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Those A delta fibers are still- They're still going up. Going up. They're in the spinal cord. They cross over to the other side. So there's an afferent and an efferent to the whole thing. Indeed. Okay. Indeed. We think of these pathways. The main one that we all learn in medical school and we think about is a spinothalamic pathway. This goes from the spine up into your brain.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's a good thing after injury and after an infection because it mobilizes all of those repair cells to come in and clean up the mess. The problem that we think is going on in pain, the switches don't turn off and go back to normal. And indeed, that, Peter, which you did a beautiful intro, is one of the things we think is playing a role in fibromyalgia.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
They got an insult, activation of this neuroinflammatory system. In a healthy state, it turns off. And fibromyalgia never turned off.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I think the short answer is yes. A little bit of the longer answer is, you know this, everything we do is weighing risk and benefits. This is one drug I am hard-pressed to come up with significant risks. We have decades and decades and decades of experience with this drug in people with addiction.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. The problem is, as all the addictionologists know, is that it's hard to keep people on this because they can just stop it and go back and use.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You have to want to be off. They have injectable versions of this. It's not called Vivitrol, is it? It's an injectable under the skin that lasts X number of days, months. But yeah, we've got a lot of long-term data on this.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And from a pilot standpoint, with informed consent, obviously, and just I would view that as a novel treatment in patients that one could try out, monitor, do some objective measures, see what you get. I want to be careful. I wouldn't say that for a lot of the things that we do, because there's real risks with a lot of the medications that we provide, a lot of the procedures we do.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Not only that, there's big costs that come with them. Whereas this, I'm going to make a plug here I have no relationship to, but we get our stuff out of Balmar Pharmacy in Colorado. Why? They're a compounding pharmacy. They've got all the certifications. The reason is you can't go to Safeway or Costco and get this.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so we go through this pharmacy because they've got good customer service. They take patients' credit cards over the phone, and they will ship it to you immediately, and they're very responsive. You can probably find it in your local area at other compounding pharmacies. It usually runs about $30 a month.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We're going to get there. But yes, if you had no C-fibers, you would still feel pain. That's one of the other things I think it's important to understand about pain is we've been trying to knock this out for untold years. And we've not been very successful with it. And part of the challenge is pain is so highly conserved from an evolutionary standpoint.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Insurance doesn't often cover it. They consider it experimental, but it's basically a free drug. It's a buck a day. Yeah. So it's one that I use more and more and more because of its safety profile and its potential for getting me a home run.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It is. And I need you to, just as ideally a good scientist, tell you that not everybody buys in to the microglial model that I'm describing. There are friends and colleagues at Michigan, Dan Claw, brilliant, brilliant guy who is very much in disagreement with me, who believes that even at these low doses, you are antagonizing the opiodergic system and in essence kind of resetting it
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
in these chronic pain states so that you're normalizing the endogenous tone. And you know what? That's the fun thing about science and why we try to keep our egos out of it. The truth will come forward.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Linda Watkins, Mark Hutchin did some really nice work in that and showed people have had some difficulty in replicating it. But I have a hard time. We know the mechanism, I think, seems pretty solid. But when I look at the clinical conditions that it has been applied to and shown benefit, I mentioned multiple sclerosis, ulcerative colitis, I believe is another one.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
and these weird neurodegenerative things, I have a hard time understanding why mild antagonism of opioids is going to have an impact on those conditions.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Well, it's another one of these weird degenerative... Through a central effect? Yeah. Yeah, I don't have a good answer for you on that. I'm just spouting off some of the headline in the studies that I've read where it's been used. I will have to go and look just for kicks when I get back to the hotel room and just see about the whole mild cognitive impairment, Alzheimer's aspects of it.
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I clearly don't treat these patients, but it is an intriguing idea, isn't it?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
About 10 to 12 people in it. This is all the physicians and nurses, the trainees. It was tiny, tiny, tiny. And we were in this small little clinic. And today? Probably 130, 150. We have a factor of 10 or more. And we've grown to be, I think, the largest academic pain center west of the Mississippi. One of the top in NIH fund. It's really come a long way.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's been really exciting to see the growth and the careers and the people we've helped out.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
As I was alluding to, back to single-cell organisms, reward, pain. We evolved over the years to have this complex experience of pain, but also redundancies. You knock out one pathway related to pain, there's others there. And they find their way up into the brain just about no matter what.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Did it do anything?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
That's a great story. I listened to that and in one hand, I remember it. And another hand, it's been so many years. Yeah, it's one of a million stories. You could have been talking about Bob as the doc. And I'm listening to this and I'm like, well, yeah, that is the kind of thing I would have done late at night and just try to get it under control.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
You could go pretty deep in there, and I get the debate. It's a great debate over wine or beer, and I understand actually taking it seriously and having that debate. A lot of different opinions on this. I actually don't engage in that debate. I think you have to, first of all, define the thing that you're debating. You have to very clearly define the thing.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Just spray the hose. Yeah. Because normally, to be clear to the audience, I would never approach that in a chronic situation like that. It lacks all specificity. You can't learn anything from it. But I remember you just being an extremist and we had to do something to help you.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
What I usually look at, I usually think of it as, I'm confident we can really help them. I don't know what help means. Curing is such a strong word. Every once in a while, we can cure, just eliminate, make it go away, never comes back.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Like your case, which honestly, I didn't even know about until recently. I was lost to follow up. Lost to follow up. I'll tell you maybe in just a little bit, like how I did find out. I don't use the word cure maybe like a surgeon would use the word because I don't want to set unrealistic expectations with patients. But I don't give up.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I've never hit a point in my career with a patient where I've ever said, we're done.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I got nothing. We've got so many tools available to us now. Back when we first met, we had a handful of procedures. We had a handful of medications, gabapentin, the new kid on the block, opioids, NSAIDs. some tricyclics, but that was about it. And by the way, that also, that notion contributed to the opioid crisis because we didn't have tools.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now, there's over 200 medications that have shown to have analgesic properties. We have over 200 procedures that we do for pain, scores of mind-body therapies. scores of complementary alternative therapies and physical rehabilitative approaches. The toolbox that we can draw upon is so much larger. Often the problem is not with all the tools we have.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's trying to figure out the right tool for the right patient, the right context. I frequently focus on getting people back to a good quality of life and giving them control of their life and their pain rather than a promise to eliminate pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
In the acute setting, often it's eliminating pain because in an acute perioperative or acute injury situation, you need to eliminate or significantly reduce it before you can get people moving, which was kind of in your case. I got to tell you, I was tempted. My memory of this was a little vague. I almost, for a moment, I thought maybe I just look up my records on Epic and just see what's what.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I'm like, no, man, that's what gets you fired. And so I didn't. I'm glad you filled in the memory gaps. I'm literally just so happy for you. Can I ask you some questions about it all? Sure. Maybe build on some of the things we've been talking about. So some of the stuff that's going on when you were in this is you were in distress.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Clearly there was a lot of catastrophizing going on, if I can draw upon that term. You cut me off if I'm going off in tangents. Catastrophizing is this concept that was introduced by Albert Ellis in 1962. He was a psychologist and he also liked neologisms. So he created catastrophizing. He created the word awfulizing. Awfulizing didn't stick around.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Catastrophizing was not related to pain, but got used for pain, has three factors to it. Amplification of pain, rumination or repetitive thoughts about pain, and a sense of helplessness or loss of control over your pain. Check, check, check. It's natural. We get a lot of controversy in the field on this term because it has such a pejorative impact.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And unfortunately, some of the docs have weaponized it against patients. Oh, you're a catastrophizer. Tragic. But it has real neurobiologic consequences because when people catastrophize, when they have a loss of self-control, when they have rumination, it negatively impacts these prefrontal cortical circuits that I mentioned, these cognitive circuits.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And in this case, our definition of pain is a rather human experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
systems so that they can no longer downregulate your pain. They have abnormal connections to hypothalamic regions, which are key in hypothalamic pituitary adrenal axis, your HPA axis, which I know you're very familiar with. And so In an acute situation, you get a release of cortisol for stress response. You know this is a surgeon. It's great. It keeps us alive. Chronically, terrible.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And so you get this allostatic overload, and it starts to thin out that brain region. You're no longer able to modulate, and it's this worsening cycle that you get deeper and deeper in. A lot of what we do in pain... is we try to break those cycles. And it's not one thing. I use the interventions, the procedures to help break an immediate cycle to get you on a path.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We do this with other patients similarly. And then it's learning skills.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, yeah.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, that's exactly it. And you had the resources to do this. I was reflecting in your book in the early chapter, you described a friend's mother, I think Sophie, and you told the story and maybe it was in the original version of it. It got trimmed out and edited. But when I read that story of this woman who shoulder injury and then went down this bad path.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And it doesn't get mentioned in the book. Again, may have been left out of the editorial, but all I'm thinking of is pain. All I'm thinking of is this poor woman probably had severe, severe pain that was untreated, and it put her down a spiraling path. And what happens in these situations? Well, one of the things we're learning more and more is social functioning.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So we call pain a biopsychosocial model, but we tend to skip over the social, small s. But it turns out we've done a lot of data analysis on our own patients. Social isolation, social functioning plays a key role in your overall pain and quality of life. And you talk about this in your book from a social functioning standpoint. My guess is she invariably withdrew. She became deconditioned.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yes. I believe firmly it is, and I'm a recovering anesthesiologist. I haven't done it now in... Oh gosh, 20 years. But when I did it, and when you were operating on a patient, the patient is unconscious. They are not experiencing pain. You need a conscious brain for the experience of pain.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
She may very well had a lot of fear avoidance around moving her shoulder, which sets you up on a worsening spiral. And what I think about, and when I think of Sophie, and I think about people as they get older, We need to manage your sleep. We need to manage all the things you put beautifully in your book.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
But I think we also need to help them better manage their pain so that they can have the function and do all the things that you say so nicely in your book. I don't know what your thoughts are.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, yeah. The data on elderly people who get a hip fracture spiral immediately downhill to death.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Oh, and I'm sorry if I'm repeating things. No, no, no, no, no.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, and I just keep thinking if we could better help get their pain under control and address them from that holistic standpoint and just get them back to a level of functioning, would this story be written differently? I'd like to believe it would. I hope it will.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
When you went through all of this, you get through the rehab, did you feel a greater, one, understanding of your pain, what was causing it, and the nature of your back and what you could do and its safety?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Now what people incorrectly made the leap of is thinking, well, they're not experiencing pain, so everything's okay. That would be a logical fallacy because all those signals are still coming from the body. still hitting the spinal cord and having their impact there, all those injury signals, because let's face it, when you do surgery, it's really nothing more than a controlled injury.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah, that's a great story and it's helped you be a better doc and help people. I listened to your story and everybody's story obviously is very different and personal. I have my own variant of this and I don't talk about this much because I tend to be a little private with these things. I suffer from cluster headaches and all my life, as far as I can remember, I would get these headaches.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It was like a bomb going off in my brain. How often? Every two years. Every two to three years. It's a classic fall-spring cycle. And all through my teens, my early adulthood, I'd get these two weeks being just terrible, the most insane pain I've ever had. I've broken a lot of bones in sports. Nothing trivial compared to that. And nothing I would do would work.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I'd occasionally go to the emergency department and they'd say it's a sinus headache and they'd give me antihistamines and they'd prescribe them. And sure enough, they worked because it always went away in a couple of weeks. I remember in residency getting one of these in the midst of a cardiac anesthesia rotation and barely able to get the patient to the recovery room.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I just went into a call room and I just hung out. The thing is, nobody knew what they were. I didn't know what they were, but I was scared. Every time these came on, I thought I had a brain tumor. I was convinced. I thought this was going to kill me. And you get really scared that it's never going away. I catastrophized.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
After the end of like a couple of weeks, I'm like, what the hell am I going to do? I can't work like this. I can't live like this. Then I become a pain doc. And I'm like, well, shit, I got cluster headaches.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
First of all, just to let people know, what a cluster headache is, it typically manifests as headaches that last anywhere from upwards of a couple hours. They can occur eight times a day to every other day. They tend to have these weird characteristics. They're under a class of trigeminal autonomic cephalages. Fancy term for simply meaning that you get eye tearing, redness in your eye.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I get what I refer to as a sticky eye sensation, like my eyelid gets heavy and it droops. I get my nasal congestion. But one of the major characteristics is extreme agitation. Extreme agitation. Meaning Beth would say, well, you better to lie down. I'm like, no, it doesn't matter. And I just pace. You pace and you pace and you pace until it goes away.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So what I did in the period of all this fear, I learned every damn thing I can learn about cholesterol headaches. Every single thing.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
It's under a rare condition. It's one of those rare ones that affects men more than women, but women do get them. You think I would know the prevalence of this too.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Yeah. Yeah. Less prevalent than migraines. Common treatments for these, there's abortive and there is preventative. What the preventative are like, calcium channel blockers that you can take, abortives, the typical migraine medications, the triptans. So I have stockpiles of triptans. High flow oxygen. So I knew I was getting one. Before these happen, I get this prodromal phase with weird appetite.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Sleep gets disrupted, I know, and a sticky eye sensation. I was giving a talk at the Napa Pain Conference, and I knew they were coming on, so I threw a tank of oxygen in the back of the car and showed them.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
If I can get it in time, if you can abort these things in time, you can save yourself several hours of absolute agony, and you can catch it in like a half an hour. So the long and the short of it is, it was through that journey of learning that I became informed and I developed self-efficacy.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
So when I got these attacks, when I knew what they were, I no longer had a huge amount of fear that would further amplify things. I was fearful it was a brain tumor. I was fearful like I was having a subarachnoid bleed. I knew what it was. It didn't change the sensory dimensions of the pain. It didn't change the agitation. But I knew even if I didn't catch it, it was going away in a couple hours.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And that gives you control. So when these happen, I know I'm prepared. I know it's going to be a shitty two weeks and I buckle up, but I know how to deal with it. I know I'll come out of it. And it makes a huge difference in quality of life.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And that's what I messages I would try to give patients is it's about learning as much as you can about your condition, being informed and putting that to use. And ideally giving yourself a degree of self-efficacy over your health. And when I listened to your story, it had parallels there. That journey that you have, you've clearly used it, maybe tried to say, make you a better person.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And yeah, I have a lot of empathy for people as a consequence.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Thank you, Peter. It's been 20 some odd years since we've seen each other. And if I can just say, I remember when I saw you, you were kind of an intense guy.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
Have you?
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I remember thinking to myself, this guy is either going to crash and burn or he's going to do something really awesome. And then decades go by and I get this phone call from Ian and he's like, dad, Peter just gave you a shout out on one of his podcasts about how you helped him. And he's like, how do you feel about that? And I said, I'm just so happy for him.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
I had no idea that he's done so well for himself. And you have. Yes, you're seeing one patient at a time and providing great care. But I think this format is reaching so many people. And this is what we need more of. We need more Peter Attias. We need you delivering these messages that are empowering people. You're making a big impact out there.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
And I just appreciate you inviting me on to spend some time with you. So thank you.
The Peter Attia Drive
#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
We still are trying to unlock the whole consciousness aspect of things, but we're inching our way there. But it wasn't enough to give that.