345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery

is consciousness necessary for the internalization of this full gamut of pain yes now what people incorrectly thinking well they're not experiencing pain so everything's okay what is the most responsible case for oral opioids I am not pro- opioid i am not anti-opioid i am propatient prescription opioids were overprescribed they were over marketed there were bad actors doing bad things but it's it's not that simple a story did it have bad consequences yes did it have good consequences hell yes i am sure everyone has heard of and yet if you asked most people to define it

they wouldn't be able to define it i'm talking about none other than fibromyalgia fibromyalgia is frequently preceded by some event societal burden of chronic pain is terrifying it's astounding it's more than diabetes heart disease and cancer combined what are the other areas where LDN is just captivating the world it 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 is there a part of you that thinks this is a guy who's going to be in chronic pain the rest of his life

or do you look at a guy like that and say "No no we can fix this." I've never hit a point in my career with a patient where I've ever said "We're done." Like I got nothing i got nothing hey everyone welcome to the Drive Podcast i'm your host Peter Atia sean thank you so much for making the trip to Austin oh it's my pleasure and it's uh it's really good to see you again after a rather long time yeah I was thinking about it so this morning my wife said "Oh who's what's the topic

of the podcast today?" And I said "It's going to be pain." And I said uh she said "Oh who you haven't?" And I said "Sean Mackey." She goes you know her face lit up and she doesn't know you she's never met you but she knows your name because she's heard me tell a story right she's heard me tell a story about my own experience through this and I then realized something which is I haven't seen you since I was in medical school yeah yeah that which is kind of weird right um so I'm sure we

will get to how you and I met 25 years ago exactly 25 years ago wow um and how you played an unbelievable role in bringing me back from arguably the brink of what what could have been the end of my life truthfully um but I want to start with kind of some broader topics around pain right so there's nobody listening to us right now who doesn't know what pain is there's nobody listening to us right now who hasn't experienced pain um yet if you ask for a definition of pain I think you'd get a lot

of using the word to describe the thing which isn't truly a definition so if you were trying to explain to a Martian from another planet who doesn't experience pain what it is what would you say yeah yeah there's the formal definition of pain which is uh 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 it's if you think of it as it's an unpleasant sensory and emotional experience and it is usually tied to something physically happening but may not be

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 you know it's either pain or reward you're either being driven towards oxygen food sex or you're trying to get away from danger and so pain is this pain is so wonderful because it's so terrible it keeps us alive without pain you know we have these as you know genetic issues of congenital insensitivity

to pain we would have never lived as a 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 and so I'm going to evoke Renee Deart 17th century French philosopher thought to be the father of modern philosophy incredible contributions brought cartisian geometry to us which led to calculus and he had this dualistic model of pain that he put forward now to his credit it was the first mechanistic foundation for pain because beforehand pain

was thought to be something mystical or um uh religious it was punishment of the gods so he put this framework together that's often illustrated this 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 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 and 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 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 so yes he got cartisian geometry right but he really you

know complete bollocks screwed it up when it came to pain this biomemed 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 and instead of it being under this guise of this separate mind and body we now appreciate it is this integrated biocschosocial phenomenon meaning that and I think this is one of the most important things that I'd like to drive across I'm going to introduce a term we're going to get

to a term called noisception which are the uh electrochemical injury signals that occur in the periphery that what goes on in the body 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 so hundreds and hundreds of years we've got we're we're basing it on Renee Deart's dualistic model we still see this in medical care right now you're a surgeon you know 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 you know how much the scalpel cut and how much tissue damage was done 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 like their early life experiences all this stuff and we'll talk about that and Sean just to interrupt for a second thinking through the the history of medicine a little bit the

the latter part of the 19th century brought a couple of other tools to pain right so between local anesthetics cocaine down to lidocaine and general anesthetics in the form of ether which finally allowed surgeons to cut people without having to hold them down while they screamed it sounds like that didn't shed any new light that was viewed in the one hand as just a blunting instrument but it didn't didn't change the model didn't change the model okay yeah had no influence on that model which just I 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 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 biocschosocial model that that's gotten much better okay so let's let's talk about is there a pain receptor yeah so let's break it down into the foundational stuff so we have

these things called noceptors complicated name it's basically a transducer which is another technical name now your engineering background so you all know that a transducer is simply a device that converts one form of energy into another form of energy this this microphone is converting sound energy into electrical energy the speakers convert electrical energy back into sound energy we have these no receptors that lie in our skin our soft tissues our deep tissues our viscera and they're specialized and they convert well different forms of energy into electrochemical impulses they take pressure they take heat cold 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 so 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 thin and slow it's really pokey 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 1 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 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 uh your brain and to give a realworld sense of the difference in C fibers and A delta fibers 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 uh coming off a curb what happened think back to that experience you get this sharp jolt of pain that goes right to your brain 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 um escape mechanisms the pain that

you experience is sharp it's well localized you know exactly where you stepped on that tack and 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 unmilinated slow getting up to your brain 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 and Sean the A delta is doing two things it's if I'm understanding this correctly is it creating the spinal reflex where I hit my thumb with the hammer the signal goes into the spinal cord out through a motor neuron to pull back without me having to think about it correct that's exactly it and um you know it is synapse and there are synapses and the vententral or anterior the front portion of your spinal cord which is your as you

know your motor part of that spinal cord they're making synapses and it's causing a classic withdrawal effect but am I also feeling the pain am I perceiving the pain and if you could do a thought experiment where you could eliminate the C fiber in an individual yes would they still feel pain yes yeah they would still feel pain so there's still a central component to what the A fiber is doing those A delta fibers are still still going up going up they're they're in the spinal cord they cross over to the other side they head

up through so there's an aerant and an eerant to the whole thing indeed okay indeed we we think of these pathways the main one that we all learn in medical school and we think about as a spinalamic pathway this goes from the spine up into your brain 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 as I was alluding to back to single cell organisms reward pain you know 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 uh just about no matter what just thinking about this through an evolutionary lens um lots of debate about this in the animal kingdom right like does a goldfish feel pain right um do we have

a clear sense as to how far from humans and or mammals you go where you still clearly have C fibers and a delta fibers you could go pretty deep in there and I get the the debate it it it's a great debate over wine or beer and and I understand actually taking it seriously and having that debate lot of different opinions on this i actually don't engage in that debate you know because I think you have to first of all define the thing that you're debating you have to very clearly define the thing and in

this case our definition of pain is a rather human experience well that's this is where I was actually going to go if I can just give you that window so you'll know what I was really going to ask is a question about consciousness is consciousness necessary for the internalization of this full gamut of pain yes you believe it is i believe firmly it is and you know I'm a recovering anesthesiologist you know I haven't done it now in oh gosh uh 20 years um but when I did it and when you were you know operating

on a patient um the patient is unconscious they are not experiencing pain you need a conscious brain for the experience of pain 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 mhm 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 yes and I just want to point out and and this is

shows you how long I haven't been in surgery but 20 years ago my recollection is an anesthesiologist was giving not just one medication but several yes so they were giving something like halathane which to my understanding we we didn't know how it worked then do we have any idea how it works today better we still are trying to unlock the whole consciousness aspect of things but we're we're inching our way there but it wasn't enough to give that we still when I say we the anesthesiologists still had to give typically a narcotic they were they

were still typically giving something like fentinyl even though the patient was unconscious they were also often giving an amnesic so that they wouldn't have any recollection of what was going on but of course we all hear the horror stories of the patient and a paralytic on top of all that right exactly muscle relaxing so you hear these horrible stories of the patient who is paralyzed but somehow conscious you you you can miss on this state sort of thing but just to make sure I understand in theory a paralytic and an inhaled anesthetic should be sufficient

to eliminate the perception of pain in a patient who is being cut yeah part of the challenge was and now here 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 um reflexes and full no susceptive impulses would be so high that it would depress one's blood pressure got it and so you augment that with an opioid understood like fentinyl like morphine like whatever and you combine those together and that's why

what the anesthesiologists do is quite magical got it so in other words you give the inhaled anesthetic just to get unconsciousness but not to fully suppress the no susceptic system instead you bring on the opioid to do the remainder of that work 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 boore they're impinging on all those brain systems responsible for stress responses so does that mean we are seeing a cortisol surge we're seeing whatever one would expect a conscious person to experience with epinephrine norepinephrine cortisol all those things still surging out in response to pain yes and in in response to no sception 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 no susception arguably more than you would ever experience i mean

if you think think about what surgery think about what we do in surgery my god take a scalpel and then take an electrocottery and start burning tissue right this is I mean there's no level of no sception you could ever experience like that while being awake unless you're in a burning car absolutely that's exactly it and it's remarkable through modern medicine that we get people through all this is a a reflection of the advancements in surgery advancements in anesthesiology advancements in post-operative care but it is no different than a controlled injury uh it's done in

a nice sterile environment but it is a massive injury that people are undergoing yeah and 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 what 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 uh that's an area that I used to research years ago many others are doing some great work in that space turns out that a lot of the factors we're

going to get to this is what people bring to your operating room table uh meaning early life events the levels of emotional health cognitive health and everything else um 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 um and we can you know there's all sorts of nuances to that yeah so let's go back to something you said at the outset from an evolutionary perspective which is pain and pleasure have been the driving factors that have been the engine of natural

selection yes and but clearly those things have had to work in preconcious models yes so that means that whatever we're defining as pain there did not include a perception of pain yes 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 I think 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 yeah

easier to accept i'm a dog person i you know I I believe they they they experience pain you move on down the evolutionary at what point right does a goldfish experience does it goldfish clearly experiences no sception they clearly have all the classic withdrawal protection survival aspects of it but what level is there a conscious brain that is translating it and also on top of it remember in our human definition of pain we bake in it's an unpleasant sensory and emotional experience does a goldfish experience emotions i leave that to the goldfish experts i you

see how you see how muddy it gets and you go down rabbit holes pretty quickly um which is why I tend to stay with humans which is which is which is hard enough by the way yeah which is So okay so how does everything you just said differ or overlap with neuropathic pain or that sort of burning pain that I'm sure some people are familiar with certainly I was familiar with it for several years yeah um is that simply a subset of this are there various different types of pain that don't have a clear um

cause effect relation to tissue damage yeah so we have different ways of categorizing pain putting it into different buckets if you will um one is no susceptive pain and you'll note that that word no susceptive sounds very similar to no sceptors and it's by design it means that it is pain caused by activation of primary noceptors whether it be in your skin or soft tissues or viscera and it tends to have certain qualities it's very easy to localize uh you know exactly where it is that has a certain intensity that no susceptive pain tends to

be timelmited responds well to short-term use of analesic agents uh acetammenophen uh NSAIDs COX 2 inhibitors uh 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 which as a former general surgeon you understood this this is due to activation of those primary noceptors in our visca now the difference and why we bring up the distinction with visceral pain that is either in our thoracic viscera or abdominal or pelvic visca is that the receptive fields that means where those noiceptors serve

and what we perceive are very diffuse and wide 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 "I'm kind of it hurts here it's diffuse." That's because the brain the spinal cord and the brain have these diffuse receptive fields which expand the area the viscra don't typically respond to the same type of stimuli that no susceptive pain does you'll remember when you were taking a boi um to the bowel the small intestine patients wouldn't normally move because the noceptors

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 um interesting characteristics with visceral pain is there's something called viscosatic convergence meaning that the apherence the information coming in from the gut from the uh thorax converge with the same sensory systems from the rest of our different parts of our body so um you know you may remember the old medical school adage uh C345 keeps the diaphragm alive okay we all we all had these in

in med school 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 and so when they had shoulder pain the answer wasn't you know 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 with the nerves that go down your arm and the nervous system gets confused 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 and by the way on visceral pain what is the response to treatments with respect to the way we saw in noceptive pain where hey great response to these NSAIDs or opioids or whatever yeah typical analesics can be helpful um but identifying visceral specific

anti-nosceptive drugs is still an area of hot research um these days it's more about trying to identify the causes of visceral pain and you know reducing substances that are winding those noceptors up neuropathic pain another bucket neuropathic pain means injury to either the peripheral or the central nervous system 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 know you know you get nerve injury from a trauma from surgery um classic qualities people describe burning

sharp lancinating stabbing shocklike um this is the kind of pain that some people tragically get after a theamic stroke in their brain you know half their body is just like terrible burning pain and it and just there's nothing going on out here it's all central um this is the kind of pain that you get and you experienced with ridicular pain andicular pain means uh in this case injury to a nerve root coming out of your spine it's this sharp radiating pain if you've got it in your lower back that radiates down in down your leg

typically below your knee into your foot this can be very challenging to treat with common analesics we tend to draw upon different categories of medications for this these are broadly speaking anti-neuropathic pain drugs um and here in our field we steal from everybody you know 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 uh gabapentenoids the taggls and their derivatives their other anti-seizure medications because they tend to have mechanisms of action that also

work on nerve pain gabapentan I think you've had perhaps some experience with um turns out it's a lousy anti-seizure drug terrible but it's a pretty good you know anti- nerve pain drug four grams a day four grams a day i was awfully drowsy though you know who gets credit by the way for making uh I give credit to uh making gabapentin the blockbuster drug george Clooney how you ever watched ER uh yeah yeah yeah he was a pediatric ER doc that's right kid comes into the ER with a skateboarding injury um George Clooney puts the

kid on Gabapenton 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 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 gapentin because nobody heard of it and then after that came out floodgates open primary care docs started using it now everybody's tried it and it's a very safe medication i have 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 payment CMS which is a public database okay neuropathic pain there's another one there's a new kit on the block called no plastic pain i don't know if this one is uh made much traction yet 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 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 nos plastic pain and it has been tied in with conditions like fibromyalgia temporalmandibular disorders uh some aspects of chronic low back pain uh irritable bowel syndrome interstitial cyitis uh and more it it's slowly starting to get traction so when we 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 yeah i

was about to say before you gave your examples I was going to say no plastic pain must be a huge bucket because it's everything for which we don't understand one of the three it's sort of the all else bucket which is enormous especially for chronic pain right you're absolutely right and I think the verdict is still out in the end does no plastic pain stick around or is the problem that in these conditions that we associate with no plastic pain medical science hasn't caught up to identify a specific peripheral driver i'm of the opinion it's

that latter like I think we're gonna find peripheral drivers for fibromyalgia there's some controversy right now as to whether fibromyalgia represents a small fiber neuropathy um 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 and uh we'll see how the story plays there's no objective way to measure pain correct oh the last uh 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 uh early research was in neuro imaging and pain it was opening up windows into the brain to see where people were thinking processing perceiving magnifying pain 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 yep over the years I migrated into this space of developing objective biomarkers of pain and it's one

of those things where this is why I love working with young smart people um I bet against it i had some young grad students and others who said that they knew they 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 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 but it turns out that there are core patterns in the brain that represent that experience of pain and so now we've others and and sorry you're capturing these through what modality 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 uh 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 and we're 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 so ju let's just start with standard understanding if you put me into an fMRI machine and I said to you uh hey

guys I'm not feeling any pain right now i feel great and then you scan me and then someone came out and took a hammer to my thumb yeah and I went through the classic response that you described earlier what would my fMRI show yeah you would see you'd see rather dramatic increases in activity in brain regions such as the phalamus the posterior insular cortex the anterior singulate cortex the dorsal anterior singulate cortex and a number of other distributed a number of other areas and to be clear this is distinct from the part of my cortex

that is the homunculus for my thumb you would also see it in S1 you're right um 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 y then we can knock it out right just go cut it out and it turns out that didn't work and it's not one brain region that generates the experience of pain 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 a typically a response to that and 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 i don't need an fMRI to see a patient and know if they have pain i can just ask them and I can use self-report measures to get at it and I do 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 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 let's Yeah I took you a little I get a little tangential okay so let's go back to the story of these these four

branches of pain or at least the first three and then kind of how they're how the periphery and yeah uh the how the how the sensory component is impacting their perception roll with that give me a little bit more i want to build off it then okay so we go back to no susceptive pain right so tissue injury occurs um I think where we where I derailed us was in classifying all the different types of pain but you had okay uh signal comes up right two signals coming up the C fiber the A delta fiber

the immediate response is to get you out of pain right so that makes there's an evolutionary logic to that right the C fiber is not there to get you out of pain because the A delta did that is the C fiber there to remind you not to go back and do that again perfect okay perfect that is basically your longerterm harm alarm that is saying Peter don't go back and do that again um 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-tooth tiger tiger because if you fought the saber-tooth tiger when you're injured you got eaten you didn't get to pass your genes along by the way do we have any evidence Sean that there was enough genetic heterogeneity around this that there were you know 200,000 years ago there were members of our tribe who simply didn't feel pain and therefore did not pass on their genes because they made poor decisions wow that's a great question one I don't know um two there was undoubtedly genetic variations

that led to behaviors led to actions that did not promote survival of the species and you know nature takes care of that those people died out i find it amazing to just sit around and dream about how much h how little convergence must have existed a quarter of a million years ago in terms of things that just ended up not being good for our species like you know uh people who didn't didn't experience pain the same way or didn't have certain filters within within themselves um you know there've been lots of talk about people who

couldn't socialize right and how where you know we we could you couldn't evolve alone so if you didn't have the right set of genes that allowed you to at least be part of some sort of social tribe and of course we still probably have people today that have escaped and and we we clearly have some antisocial folks among us but they're the exception and not the rule so anyway I just wondered if um today we're much more homogeneous in terms of what a human's response to pain is versus what it might have been probably and

when you go back through some of the lower animal species what happens when one of those animals gets injured in the wild you know and again I I'm not a animal pain expert but typically they're set off they're ostracized those 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 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 and I also think about certain things like um child birth prior to any anesthetic was obviously brutal uh both in terms of the pain and the mortality and yet there's no evidence that like you know people were deciding yeah maybe we not ought not to do this in other words the drive for procreation Yes somehow overcame what must have been you know brutal absolutely and I got to tell you hats off to half the population that are women that that and the women that do this uh

I can't imagine I don't want to even go there there is interesting protective aspects during childbirth that doesn't take away necessarily the pain but I I think some of the uh estrogens estradiols has not only an analesic effect but I sometimes just swear they don't seem to remember sometimes just how painful it was and yet we do it they do it again yeah yeah those are the two things that I joke about with my friends which is I still don't really understand how our species is here for two reasons one women had to continually go

back to the well because remember if your reproductive rate isn't in excess of two the species collapse so on average every woman must be able to do this and back then it had to be a reproductive rate of north of three right every woman had to do this three times how she did it the second two times after how bad the first was blows my mind the second thing is just looking at how stupid adolescent males are uh I'm sure you can relate to this i was one yes as was I and I look at

my boys i don't understand why males all didn't die from just doing stupid stupid things before the age of 20 because you know I mean or even before the age of like 15 so it's like those two things are a miracle to our species that all the males didn't die and that all the females were willing to have at least three kids i repeatedly tell Beth I'm like I I sometimes wonder why I was not a Darwin award winner if you've ever read I remember the Darwin awards fondly yeah we'll link to them in the

show notes some of my favorites um 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 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 uh one of the main one is the phalamus 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 um the anterior singulate cortex now the anterior singulate cortex each of these brain regions has some functions associated with it uh the anterior singulate 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 antios singular 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 because in essence our

brains are prediction machines um 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 that singulate cortex as a salance detector is triggering and it's putting into action for me to withdraw other areas of the brain include the insular cortex which uh 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 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 emotion your state your emotional state and what you're thinking now there's also connections with your your amygdala this deep um primitive region of the brain involved with both um threat detection as well as reward and it's

connected uh 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 and at this point in time I really haven't done more than Renee Deart has in telling this story because at first pass the brain is still remaining a passive receptacle just taking these inputs right 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 now in part this was first described by Ron Melzac and Patrick Wall in I think it was 1965 the gate control theory of pain brilliant guys never had the pleasure of meeting them but you know they they just did seinal work and this gate control theory of pain you know posits that yes you have aerent 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 uh and systems from your brain so let me give you an example to this we let's introduce another nerve fiber type a beta a beta fibers are your touch fibers when you touch or scro stroke your skin um 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 fibers 1 meter a second a delta fibers 10 a beta fibers 100 meters a second fast that's why you

can dance 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 before or after swearing there you go um a lot of people swear so it's after swearing you swear and then shake it shake okay you

You're a shaker some people squeeze proximal there you go you squeeze you shake it sometimes you run it under water what are you doing when you're squeezing it and shaking it sometimes trying to create a distraction okay um sometimes though probably illogical trying to keep whatever humor is in there that's hurting isolated like a tourniquet right right uh obviously if I'm using cold especially if it's one of my kids that hurt themselves we'll put cold on hoping to anesthetize the area presumably slow the circulation take down the swelling yeah you're that's beautiful when you're talking

about longer term things which are all perfect um because cold does those things and also cold by the way reduces action potential velocities and firing in those AD 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 no susceptive fibers you're not really impacting it there that horse left the barn that horse left the barn And that horse is you got horses still running out the barn you're 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 they're coming into a slightly different area of your spinal cord and they're sending over projections into where those no susceptive 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 it's a beautiful example of neurom modulation

you're doing your own neurom modulation 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 yep tens is TENS transcutaneous electrical neural stimulation now what TENS frequently what it originally did there's been modifications of it is when you turn on the uh you what you do with the TENS and 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 neurom modulatory effect back in the bra in the spinal cord pretty cool when it works and how do you predict patient comes to you and they're experiencing some pain what are the what are the clues that would tell you I think TENS is going to be successful here in other words I think that activating a beta fibers is going to be a tool that will reduce your perception of pain because that's what we're doing right everything that you do is how do I reduce your perception

of pain i can't take I can't necessarily take away I mean if they have an injury that needs to be resolved they shouldn't be seeing you they should be seeing the surgeon or whoever fixes the physical injury right in short yes i 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 you know I'm I'm 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 um so who is the I hate to use the word poster child but who's the patient that when you see them your intuition says TENS is going to really work for this person somebody with I think more you know it's no susceptive muscularkeeletal pain i tend to think of somebody for whom TENS is more likely to work something that has more of a classic no susceptive type of pain problem beyond that it's Peter it's a trial and error and 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 gate control we talked about TENS can I put a bow on the gate control thing to make sure I understood it yeah because we it seems like a very important idea but I also think I might be missing the the juice is the idea that 10 people could experience the exact same peripheral injury if you could map the um the action

potentials they would look identical you could even see identical perceptions but they're they have they could have 10 different gating channels within the spinal cord and therefore perceive pain differently i just want to make sure I've captured what the gating theory states you are right you're right with that individual um variability in pain we haven't talked about the brain's role in the gate control which we're going to get to but just getting to your question there's been some elegant studies guy named Kim years ago um did a beautiful study where he applied a 48° C

stimulus to 500 people 48 degrees C i think it's 121 degrees Fahrenheit somebody will look it up and you apply it to the u the arm the hand and then ask "What's your pain score?" And what he found was a perfect distribution of people who said "Nah this ain't painful ain't nothing." And they had that's like zero one out of 10 some were like "Yeah it's a little painful two or three." And others were like "A little more moderate four five six." 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 i can't call it an experiment because I'm not getting IRB but when I teach the neuroscience class around pain um I bring in an a circulating ice water bath it's um 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 yep so a circulating ice water bath and I asked them to dip their arm in for 15 seconds pull

it out whisper in my in our research assistants ear 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 could keep my hand in there all day." 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 no sception may have little to nothing to do with your experience of pain and why that is so important for health care professionals to understand is because for so long we have projected our own experiences onto everybody else so here's another experiment that you won't be able to do unless you get to teach this class on multiple days but it's to go one step further which is to do the same thing every day and see how they compare their score from day to day i'll tell

you my experience with that i I do love to use a cold plunge okay so my cold plunge is at 42° with circulating water so I don't know what that makes it feel like but it feels like it's somewhere in the 30s there are days when I can spend 10 minutes in there and feel like nothing is wrong there are days when I'm not kidding 30 seconds in my ankles hurt so bad I want to scream and I think what's different like it can't be the circulation in my ankles is better one day to the

next they're a relatively avascular part of my body why is it that one day I I can spend 10 minutes and not know I'm in this water i mean I know that I'm cold but it's more like my core temp but my joints don't hurt and on another day the throbbing in my joints feels like somebody's hitting them with a hammer and I'm the same person so so in other words I your point is well taken but I would say there's a second dimension to it which is even as individuals we can experience things differently

from day to day 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 um the um anterior uh singulate cortex being some of the more emotional as primary semataensory cortex the homunculus being more sensory the insular cortex has an introsceptive state it's like our internal awareness of our bodily state uh we talked about um the amygdala now let's introduce also the prefrontal cortex the prefrontal cortex the big thinking part of our brain up here both the vententral medial

and the dorsal lateral play a key role in our modulation our cognitive control of pain and these systems the prefrontal cortex the anterior insular c sorry the insular cortex the singular cortex all have those descending projections back down to the spinal cord so we talked about the gate control theory of pain in the context of rubbing your finger out here a peripheral neurom modulation where it really comes into play is when you introduce brain systems 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 um 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 and maybe we'll talk more about the intersection of sleep and pain may you know but huge research in that space um you know your your state of uh uh of you know of anxiety apprehension around this your um all sorts of cognitive emotional aspects weigh into your uh 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 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 the within person daily variations over time and model that now there's there seems to be kind of um like a I guess I should ask this because I don't I'm not asserting this as the case is there kind of

a moral judgment that comes to this at some level like don't we as a society just tend to look more favorably at people that have a very high pain tolerance so when you go through that experiment you just did with the medical students if everybody's being brutally honest aren't they kind of looking at the people who score 012 more favorably than those that score 8 n and 10 absolutely why do you think that is because if I'm being truthful I do it yeah yeah that's what society values that's that was my home life growing up

that's what my father expected i come from a very working class you know 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 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 our society is is

that a male thing exclusively i think you need to get some women on the show and ask them um I think I think it crosses actually i do think there is a masculinity aspects of that 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 uh sensitive but you know we're getting a little out of my wheelhouse on that but you're you're you're absolutely right

i I just think it's like a compatibility thing like I know when I do that type of an exercise compared to others I tend to just feel less pain i also know my wife does as well and and so I almost wonder if that's a compatibility like we both just have a high threshold for that when we're exercising when we're doing anything even recreationally that doesn't matter my uh partner my fiance we're now engaged um is a professor at Stanford Beth Darnell and uh she's an ex ultramarathon 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 I I'd ask her like 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." And I similarly grew up in an environment where you know you learn to be tough and you learn to power through life's adversities so what is the consequence of this so we're acknowledging that it is an attractive trait to have a high tolerance of pain

society rewards it and yet by definition a significant subset of the per of the population call it a third call it a quarter if it's a normally distributed function are going to be a standard deviation on the other side right they're going to be in the they're going to be on the side where hey they're relative to people who have a high tolerance for pain these are people going to really perceive pain and if we just did this through the lens of the responsibility of the medical community there's a pretty significant consequence to that right

indeed now 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 uh so just because you have a high threshold for cold you could completely flip it on hot or pressure or pin prick or whatever the other modality is as 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 uh I've had you know these thermal devices on me where I've been there and

ended up with second degree burns um define my seven out of 10 i hate the cold i hate the cold i'm a I'm a wuss when it comes to the cold it's why I live in California uh it's why I lived in Arizona um 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 i was going to say is there any way to put together a set of experimental lab versions of this to

basically generate predictive models of how people will respond to real world pain and I was I think where you're going with chronic pain is even more relevant right so for example why do some people have a disc herniation that leads to you know manageable pain whereas for others the exact same injury by every metric available to us produces a totally different set of consequences and what do we do about that and because this is now where we move out of that dicardian 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 uh a zero or one on the dial some might be a 10 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 um athletes learn how to manage their pain and suffering um 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 they align with a lot of the stuff in your book so you know there's 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 uh amplified pain what about other things you talked about sleep deprivation any other physical things exercising not exercising uh insulin resistance non-insulin resistance type like what are the other things that might factor into this yes

yes yes one of the biggest predictors of diabetic neuropathic pain is glucose control so you know 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 um causes injury to those no susceptive fibers and also uh causes injury to the a beta inhibitory fibers and so we that correlates with glucose control by way of example uh diet plays a role uh because if you're eating things that are causing inflammation We didn't talk about all of the stuff

that amplifies or winds up those peripheral noiceptors we treated those as a static thing when they're not they're dynamic so in the face of uh of inflammation um that causes something called peripheral sensitization you've turned up the amplifier on that noisceptor in the periphery [Music] uh sleep uh eluded huge topic how much sleep deprivation does one need for for there to be an increase in pain perception oh well let me listen you we're both out of residency long enough but we we've both pulled our old nighters how did you feel the next day i mean

I felt awful but there was you know there's interesting that there you felt worst between 5:00 a.m and 8 a.m and then you get this second wind usually about the time you're operating right uh and and and then you usually feel pretty good okay um but but overall I mean it's a it's a haze it's a haze and you're just powering your way through it and if you think about it you know 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

at least I don't 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 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 yeah

for sure you're human um that impact on sleep ultimately further amplified your pain um on top of it did you how did you feel during that and outside the pain how was that affecting how was that affecting your overall life and your thoughts and your emotions total disaster in what way well I mean look there's so much going on i mean we can I'm happy to tell my story because it's a great introduction to to kind of the the work you've done so for folks that haven't heard it and I I've shared this before and

we were talking before the podcast I don't remember how much of this is in the book because at one point I wrote all of this out i'm pretty sure much of it got cut out but um when I was in my third year of medical student I was having just a great old day uh rode my bike to the gym was just about to go to the gym and I get off the bike and I feel a pain in my back like I've never felt before and it was enough that I decided not to work

out which says something because I would have worked out through any amount of discomfort i limped home laid down and said "You know what i'm just going to sleep this off and tomorrow will be fine." Tomorrow wasn't fine i was in so much pain I couldn't get out of bed had to actually call my roommate we had separate phones in the same house to come and get me up and out of bed and the next two weeks proceeded to be a really unbearable episode where I was doing an ICU rotation and you know this is

back in the wild west where I think the nurses and the residents were just shooting me up with tord doll every day non-stop getting me through the day but the nights were brutal and what I now realized happened was I'd had a really significant herniation a piece of that L5S1 um disc broke off i would later find out it was a 5cm piece and it had extruded broken off was sitting on the S1 nerve route every night now I was going to pain going to bed feeling as though the skin on the bottom of my

foot was being ripped off so the the only way I could sleep was to put my bag my foot into a bag of ice and take some amount of benadryil that was enough to knock me out this went on for about another week until the dean of students saw me limping along and said "Hey Peter what's going on?" I told him this was a Sunday afternoon i was studying he took me directly to the ER got an MRI showed all of this mess the next day I had surgery as I've talked about in the past

everything went wrong in a series of surgeries and fast forward three months three trips to the operating room multiple disquectctomies laminottomies multiple levels in theory my back should be fine i'm anything but fine i now have a new pain but this is unlike anything that was related to my back this is where you come in i now have a pain that is so significant and it sounds grotesque to explain it but this is all it was it felt like someone was reaching in my body from my kidneys into my groin and tearing my testicles out

from the inside of my body so needless to say I was out of commission i did not move i laid on a floor 24/7 um and to your point how did I feel well it wasn't just that I was in so much pain that I couldn't do anything it was I watched my life disappear so it went from you're not going to graduate from medical school on time to you're not going to get to do a sub internship in surgery to you're not going to be a surgeon to you're never going to walk again so

by that point the overlap was how were the opioids that I was being prescribed to control the pain tripping into these are a tool to numb me to this entire experience so at this point I and I've talked about this in the past at this point I was taking over I think I was up to maybe 320 milligrams of Oxycontton a day which is kind of amazing because if you and I took that today if you and I split that right now we would die so that I'm you know that I'm mainlining 320 milligrams of

Oxycontton a day just to you know blunt the emotional pain of this yeah um I think says what we need to know we can come back to the story of how I met you and and and what how my life turned around from that point and it's still a miracle for me to believe I actually graduated from medical school on time despite that all happening now into my fourth year because this was my third year uh bleeding into my fourth year of medical school when all this was going on it's kind of amazing a difficult

time third year is tough but anyway so we'll come back to the what happened but that's a long answer to a question which is at some point it wasn't even about the pain the pain was unbearable but it wasn't the most unbearable part it was the expectation of what that pain meant for the rest of my life that became much more unbearable it's a terrible story and I have to imagine one that is probably shaped you moving forward and you know had a big impact on your life and what you've been doing i call it

the best worst experience of my life more more best today the gratitude I have for that is I mean again I wouldn't want to do it again but it has been such a positive impact on my life yeah yeah well I hope we can come back to that um 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 like everybody else's life out there uh and I think

there's some key messages there um what would you like to segue to before we go into kind of like the ins and outs of what pain doctors can do yeah let's just talk about some of the breadandbut stuff on pharmarmacology okay right so how how can we navigate our way through what NSAIDs do what opioids do what COX 2 inhibitors do what should people be aware of in using these things obviously opioids are a remarkably controversial topic but there's probably a nuance to it that's missing from the broader discussion um but why don't we start

with a softball like NSAIDs how do they work you know everybody's heard of Advil you know Alie neproxin all of these things sure so these uh these medications are uh cycle oxygenase inhibitors they reduce uh prostaglandins they red they what they do is a couple 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 out in the periphery during injury that wind up that that noceptor and amplify it prostaglandins histamines cytoines interlucans all of that this inflammatory soup that occurs after every single

surgery every single injury that we experience you get this inflammatory soup and it's classically classically mediated by swelling redness temperature increases and aspirin and a COX 2 in uh COX 2 inhibitor NSAIDs do a nice job in reducing that inflammation now this this is where medical science I I I you're going to probably be much more informed on me 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 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 nonfusion of that joint to the bone they were getting failures hm 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 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 uh in the world 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 but an 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 you know if it's if it's helping with that level of functional improvement now are you talking about this through the lens of acute acute pain or only through the lens of chronic pain at this point a little of both but I think through uh chronic pain we start to introduce all the broader the longer term negative consequences of this you know impact on blood pressure your heart impact on your kidneys

with long-term NSAIDs particularly if you're older um I remember I think it was in your book you took Vio yes i loved Vio i did too and I still remember the day in oh god it must have been December 2001 when the FDA came down and said no more Vio and I looked at my last bottle and I was like oh god no 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 and so

I ran out a stockpile of that for a long time and you know this is another classic thing if you you can cut this if it's too tangential but you know every field looks at the problem through their own lens here you had a drug that was causing um heart attacks well I mean in the world's most susceptible individuals at a relatively small absolute rate yeah i've already had this discussion with Eric Toppel which was like mistake net negative oh was that right absolutely net negative so yeah cuz I've always wondered Merks is faulted they

should have been much more transparent about this put a blackbox label on it and we should all still have access to Stop using the 50 milligrams use the 25s and you're right don't give it in susceptible people and I think it's a class again yeah the baby got thrown out with the bath water on that one and it's a you know it's a 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 you know save the heart screw the kidney and so yeah a great drug wish it was still around why do you think there hasn't been any drug that's come close to that like Celre is a joke like none of the none of the none of the drugs that are in the Extra had a Valdeoxib I think it was little bit close but I think it if I remember it had a Stevens Johnson uh a bad rash with terrible consequences i think the drug companies get scared of the lawsuits uh oh

so so NSAIDs uh nuance around taking uh the the vertical do you have a version on on dose i mean do you say 800 milligrams of acetto of um of ibuprofen TD three times a day 24,400 milligrams would be you would tolerate that for how many days if a person needed it yeah uh you know a week to two weeks on that make sure you're eating yeah 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 you know don't just go into this stuff

blindly yeah it is interesting that we can buy acetammenophen and ibuprofen over the counter and yet they can cause a ton of damage if not taken correctly i mean the ERs see people with uh acetaminophen Tylenol overdoses and you know it's a cause of uh well you know liver failure liver failure now um let's talk about acetaminophen for a while when I last tried to understand it there was no clue as to how it worked do we to this to this day do we understand how it works minimally more information and I haven't and full

disclosure haven't read up on it a lot i know it has some cycllo oxygenase um one impact a lot of it is thought to be central um I haven't tracked it much beyond that i saw some interesting the side studies where it seems to have some impact in the brain around emotional uh modulation and so there's a degree of emotional blunting on acetaminophen now whether it translates into a real world or if it's just an experimental manipulation I don't know but but there's a nice synergy with acetaminophen and ibuprofen because different mechanism of action different

organ systems are impacted so you can take less of each when you combine them what's your take on that i think you just said it Peter I mean you said it beautifully i use those in combination to get the twofer uh to get that synergy the one plus one is not two but three so you can take uh Tylenol historically we would say up to four grams a day y um more recently there's been some push to try to reduce that to two grams a day uh clearly if you've got liver dysfunction if you are

drinking large amounts of alcohol um less yeah my go-to stack if I am actually in pain like if I'm having like I uh a year ago I had um I had to get a crown replaced yeah or sorry I had to get a a crown put on a tooth that had an old filling that broke and it's the funniest thing um because of how remarkable the teeth are at Sensation but the crown was a little too high okay okay so what's the impact of that that meant every time I took a bite that one tooth

was bearing the brunt of it it was the last tooth I had right in front of my wisdom tooth and I'm talking to my dentist and he's like "Yeah Peter it's just too high just come in and let me shave a little bit of it off." Well I didn't have the time to go in so for two months I did not go in to get this thing shaved off the pain was un This is how stupid I am like I couldn't spare the two hours to go to the dentist in a and he was willing

to see me nights and weekends this is the most accommodating dentist in the world everybody should have that kind of dentist tony Pacheco i can't say enough about him and um and yet I couldn't make the time so for two months the pain got so bad that I eventually couldn't chew on that side at all so my point is I had to be taking something to get through the day and the stack that worked was uh 400 of Advil 500 of Tylenol three times a day okay took care of me now let me ask you

does ibuprofen work better for you than naperson i don't know but the reason I prefer it is that I can line up the dosing with the obset menophen because I believe napin you only take once a day right twice a day twice a day okay but you're you're right i wanted something where I could do it T instead of B sure the reason I ask is I find huge individual variability in responses to NSAIDs okay naperson works beautifully for me at 500 twice a day ibuprofen not so good at at what dose uh 800 three

times a day wow yeah with food uh and water are there types of pains people should be thinking of where these things work especially well and other areas where yeah that's just not going to have much efficacy i don't find it as effective in neuropathic pain it might take a little bit of the edge off um no susceptive pain typically is your go-to you're kind of your no susceptive or your no susceptive inflammatory pain the kind of pain you'd see in a joint those are your typical go-to forms of back pain particularly you know in

acute situations but also somewhat in chronic and you know 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 and I think in part it has to do with a little bit of what we call pharmacocinetics or where the drug is getting and different NSAIDs can permeate different tissues

at different rates so you're saying it maybe we should be empirical in other words try the neproxin try the ibuprofen figure out which one works obviously don't take them together obviously don't take them together but your take-home message is spot on do you have a concern with people taking acetaminophen and consuming alcohol do you tell people to refrain from alcohol when they're taking Tylenol i tell them no more than I I I just said a conservative listen don't do more than like a drink a day you know is that the right amount i don't know

but if I tell them one drink a day they'll go do two and uh they're probably still okay with uh with that and then I am looking in their chart just to make sure they're not drinking four or eight or and there's liver issues what do you do i I typically when I'm taking acettomenophen where I don't drink much anyway I'm probably going to have four drinks in a week um so um meaning four days a week I will have a drink or three days a week um but if I am taking Tylenol I'm just

going to refrain um again I don't have any evidence to suggest that that's necessary but it's it's the precautionary principle at its finest um okay I want to talk about muscle relaxants so the other thing that has been a real uh favorite tool of mine is blephin now it's not a particularly potent muscle relaxant um but it seems to for me and for the patients of mine in whom it works offer something that something really potent like volume doesn't bring all the baggage of of of a benzo yeah or even a flexer where you can

kind of get the drowsiness and frankly a lot of people just I mean I used to even get nauseous on flexer but something about blephin I don't even know it's in me at 20 milligrams twice a day but it actually takes the edge off and where I typically find this beneficial is if I slept wrong and I get a kink in my trap or I've been on a super long drive and my QL's sort of flare a little bit and I know that if I had all the time in the world I could go and

stretch my way out of that but sometimes I just don't have that time and I need to kind of get right back to doing something awful like sitting and just you know 2 or 3 days of 20 milligrams of blephin B with a little NSAID and like I'm as good as new and I save myself the you know the real flare up so what what are your experience with muscle relaxants beautiful case example by the way for yourself of how we would use those um blephin is one of the safest to use it is not

habit forming like the somas yep and others that can be uh like a barbbiturate can act and people can get highly psychologically dependent on them the flexerils have a uh anti have a triccyclic anti-depressant property about them that may sometimes be helpful for people in various mixed pain states but also can cause sedation y the blephin seems to be pretty benign um we don't typically use muscle relaxants for longterm chronic conditions the data hasn't borne out now with that said so how many days are you comfortable with a person Oh I'm I'm comfortable with a

person being on back in all their life to be oh yeah yeah it's just everything I'm doing I I know I'm 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 Backton i don't mean monetary cost it can cause sedation what do typically or is it just individual i think it's it's individual and obviously it is dose dependent the higher doses more sedation um we can use

blephin intratheally we put inthecal pumps for blephin uh this is a beautiful lifesaving minimal surgery that we do um for people with a spinal cord injury intractable spasticity uh because to get the spasms under control with oral doses you just can't get there so we we put thread a little catheter into the CSF and we deliver blephin that way now it again is a clean relative 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 and I I know you do the same types of things in your practice so um we use it we can use it in acute subaccute we'll use it in some chronic conditions uh as a trial what's a trial month two months okay and then we monitor data on every single person and what dose are you comfortable up to 20 milligrams three times a day yeah up to 80 milligrams I believe is kind of the upper end I don't usually get there okay um you alluded to

neurontin earlier and you alluded to the fact that it played a role in my recovery because once we got the big stuff out of the way i still had a couple of years of peripheral nerve injury and the only way to put the fire out in my foot was Neurontin and unfortunately it was initially it required four grams a day i was taking a gram four times a day or something like that and the good news is it worked the bad news is you're pretty much always tired so I was very happy over time to

get that dose down and I think within 18 months I was completely off the neuron and lo and behold never experienced although interestingly maybe once every year I get like an enormous surge of fire into that same foot literally one shot of flame that lasts seconds and it's gone but essentially never again um is neurontin still a very powerful tool in the use of neuropathic pain you alluded to other drugs like anti-depressants as well um in addition to a rather impetent anti-seizure med but yeah what else what else do you have at your disposal for

this type of pain the beauty of neurontin or gabapentin and its um cousin pregablin uh which was introduced immediately after gabapentin's patent ran out so conveniently very conveniently um both have the same mechanism of action they work on the alpha 2 delta subunit a calcium channel in the spinal cord in the brain that's a little um too jargony and technical but think of them as agents that turn down uh the signals that are heading out that are in the spinal cord being processed and in the brain so they're really not impacting your nerve out out

here or in your leg um they can be very effective the beauty of these two drugs is uh there's no lethal dose like 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 um it's a little bit more nuanced than that because there are side effects yep you

can fall asleep driving you can fall asleep driving i tell people don't operate heavy machinery don't go you know doom buggy riding don't blah blah blah um there is in elderly patients in particular uh I warn them about falls because you can get a little unstable now pregablin can also lead to weight gain right doesn't it also increase appetite both of them do okay well it's more I see water retention got it i see a little peripheral edema in both and they also both enhance sleep especially pregablin and so there's there's a little bit of

an added benefit to patients who were using these to also put the pain out at night when it can be most noticeable um there was actually a study I I I don't know if I'll ever be able to find it it was sent to me that actually suggested pregablin didn't just make you drowsy which was obvious but but also promoted appropriate sleep architecture 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 um I have uh I have taken it

uh after surgery and uh I find that it makes me sedated i don't find the quality of the sleep I I mean I could I could be I could be totally wrong on that but No well we both could be your experience that's it that's it it could just simply be my experience the truth is uh I do tend to when I dose it I'll dose lower in the day and then I'll wall up a little harder at night for the very reason so let's imagine gabapentin you know maybe in the day 300 300 600

at night mh and I'm trying to titrate that so that one it helps some sleep 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 so yeah I do use it to help people sleep um no lethal dose uh maxes out at around

900 to a,000 milligrams at a dose because it's it's taken up by an active transport system in the small intestine once you take more than about a th00and milligrams the rest of it just passed out your backside pregablin is different it it has a 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 pregablin where I can drive more into their system and again you're using these for the most recalcitrant neuropathic pain typically i'm using these for the most recalcitrant pain in general so that's an important point um while I can speak to peroperative pain acute pain subaccute 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 and so by definition what's the We didn't even do this i'm sorry we didn't define chronic pain but how would you put a definition

on that there's various definitions and some like to put a time frame on it which I think many of us believe is a little artificial it's not 3 months or 6 months it is pain that persists beyond the expected time of tissue healing so it is nuanced it's context specific meaning if you have an ingral or hernia repair or a prostatctomy which you know should heal up pretty quickly and your pain should go away pretty quickly but if you've got pain after 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 that is a massive massive surgery and you're going to have pain for quite some time so I wouldn't call that I wouldn't call chronicity for a total knee no it makes sense totally makes sense context specific um this gets into also some of the whole issue around opioid prescribing and these rigid time frames for surgery and and what have you but persistence beyond the time of expected tissue healing anti-depressants and their role in pain management yeah these are incredibly effective

agents not necessarily for their anti-depressive properties they frequently work through modulating a couple neurotransmitters serotonin and norepinephrine and to varying extent we find that the classic what we refer to as SSRIs a serotonin the selective serotonin reuptake inhibitors haven't been as effective for pain as the older dirty drugs of the triccyclic anti-depressants we call them dirty which simply means they act at multiple receptors they hit multiple systems so these triccyclic 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 do you remember how much you gave me of how much sodium sorry how much lidocaine back then i hope I hope it wasn't toxic uh well I'll come back to the story it's pretty funny i'm looking forward to it um which which TCAs uh are the are the popular ones everybody you know there's I think there's about nine what are your top two or

three yeah that's the thing we all get comfortable with our top two or three of any class and so mine's my go-to is diproamine norripalene and amatipptalene um they're broken up into different categories based on mainly side effect profiles so the after noraleneal what was it uh amatipptalene yep yep so elil is 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 cuz 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 have I had that happen yes and I still embarrassed to this day um but if I have Is it offset by GLP1 agonists in the modern era oh you know this was 20 i learned my lessons i haven't I haven't run that experiment that's a great idea but I typically use the amitryptalene when I need some sedating help at night for sleep and pain because

it dual the dual action i like the dipamine because it has less of that histam that sedating property and I'll tend to go to that and the norryalene um and you can titrate blood levels for instance like the norpalene and those drugs so where do they work they work in the brain they work in the brain stem one of the classic um areas down deep in the brain stem is a rostal vententral medularary region where descending pathways are coming down and some of the key neurotransmitters there serotonin and norepinephrine so we're not necessarily using these

drugs for their mood changing properties 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 when we prescribe them an anti-depressant is like okay you know uh you know Mrs jones Mr smith we're not doing this because we think we're you're depressed and that's 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 yeah not

not FDA approved drug uh approved for pain is what you meant yeah thank you thank you for that they're FDA approved for something else you're you're you're absolutely right okay well this brings us to opioids which I sort of saved for last because of the uh well there's actually more drugs I want to talk about but in terms of like the off-the-shelf typical stuff that people think about so um a lot of hay has been made over this um there's no question that um opioids have been overused and abused and there's no question that um

illicit use of these things has had a devastating uh impact on our society um but it would be difficult to say that the field of medicine would be better off having never had an opioid to you know we just talked about surgery for example very challenging to deliver medical care in a hospital without opioids so the question becomes what is the most responsible case for oral opioids which by definition are meant to be used outside of a hospital not inside a hospital um and as a pain specialist I I would imagine few people are better

equipped to navigate the nuance of that question yeah it is a very nuanced question um 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 yep uh I don't take money and of I am not pro- opioid i am not anti-opioid i am propatient i view them as a tool i view them as a tool much like the other medications interventions mind body physical rehabilitative complimentary tools that we

use they have a particular place i have a personal deep 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 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." Cuz my approach is avoidance with that said I have learned a long time ago not to project my personal experiences onto my

patients that had to come through age wisdom whatever um it is true prescription opioids were overprescribed they were over marketed they were you know there were bad actors doing bad things it came at a time but it's it's not that simple a story i 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 yes um you had a letter to the editor of New England Journal saying that nobody got addicted to on a like 38 patients or

some nonsense and Purdue and others ran with this i 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 um there was growing pressures to do something about it uh people have brought up the pain as a fifth vital sign as an example and people have different opinions about that uh 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 but also there was other pressures and Peter you were you witnessed those firsthand what was going on back in the 90s and the 2000s and 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 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 a bucket of whatever and the reason for that was surgeons and docs don't like getting called at 3:00 a.m for pain control so pressure to put people out in the uh in the home environment on top of it docs get lousy training for pain like what is the average seven hours I think uh in medical school vets by the way 40 hours of pain so great if you've got a dog

not so great for patient so you got this pressure and by the way not only that 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 gaining and patient satisfaction scores 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 so there's 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 by the way the perfect analogy to this is the uh mortgage crisis uh in 2006 to 2008 where if you took a zeroth order view it would be really easy to blame one of the entities but it is actually a perfect storm right i have a slide yeah on the opioid I call it the perfect storm uh you're absolutely right and in the end and here I'm going to be a little bit reductive when it comes to the doc's roles in this and I'm going to borrow from my friend uh

Professor Keith Humphre there are three kinds of physicians in the out there there are the majority of the physicians doing the right thing for the right reasons 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 bad those people at the top take away their license put them in jail 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 um they did they contribute to the problem yes uh have they gotten educated have we um yes i didn't answer your question though and let me now circle back and and I hope you'll forgive that little bit of saliloquy uh on my perspective of that 20 years um I don't use opioids as a first-line agent ever almost never uh end of life cancer but usually by then they've tried other things before they're getting to us and uh

I will use end of life cancer pain i'll use opioids liberally as needed now just one thing Sean you are not taking care of somebody in the acute phase of expected pain typically is that correct in other words that guy that just had a knee replacement he's being managed by his surgeon correct yeah frequently uh we have an acute pain service in the hospital that sees about 30 to 50 patients a day based on what when is a patient being when is the big gun of your team's expertise being brought in for a postsurgical routine

case versus not when 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 m you know when we brought pain in for every case when I was in residency uh was uh anytime we did a thoricottomy it was a non-negotiable yeah pain was consulted before the case just for people listening a thoroctomy we didn't do these often because a lot of times by the time I was in residency we did minimally invasive surgery in the chest but sometimes you

had to actually make a huge incision uh under the ribs and that's a very painful we just you know you just know this from experience that that's such a a painful experience you you cut this huge incision in the intercostal muscles you put rib spreaders in you crank these things open so you can do this big operation we just know those patients are going to need an epidural catheter and we want that in before surgery not after and it makes all the difference in the world so pain was a part of that response i don't

remember us routinely bringing pain in otherwise but things have changed I'm sure in 20 years so today for a general abdominal case or a general orthopedic case are you brought in pre-operatively yeah yeah these days there's a lot of movement towards these ARS protocols and enhanced recovery after surgery and so um fortunately the field of medicine is moving more and more towards a team-based healthc care model where you know surgeons um pain docs anesthesiologists nursing rehab are all working in a collaborative manner they're putting together protocols to what is the best optimal approach to prehab

a patient before surgery move them through the uh intraoperative and then peroperative 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 catheterss and this is where we're running that local anesthetic the numbing medication that stops the nerve impulses to provide pain relief after surgery um and so yes we do get deeply deeply involved in that acute surgical pain space and then also with internal medicine docs and the when patients

are admitted into the hospital for whatever cause so if someone's listening to us and they're going to have elective surgery at some point like I want to plant a seed in their head for someone who's going to have the knee replacement the hip replacement the colacyctomy the appy whatever should they be requesting this of their surgeon should they say "Hey I want to be diligent about my recovery i want to minimize my use of narcotics do you mind calling in a pain consult so that we can I can just have a team of docs who

are exclusively thinking about my pain?" Because let's be honest the surgeon I got enough to worry about i got to make sure you didn't leak that that anastmosis is fine that you're not getting a wound infection your pain is literally like third or fourth on the list of my concerns for you to have the best outcome you are right and if uh 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 uh what will pain management be like

is there an opportunity to interface with an acute pain service particularly 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 pre-surgical plan for them which will often include a regional anesthetic approach meaning those those nerve blocks or the catheterss we sometimes involve um uh introvenous ketamine to augment we will uh 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 all of this is not just solely to reduce pain but to put that person in an optimal state for rehab for functional recovery how ubiquitous is the uh the patient controlled an analesic device the PCA that we used to run everywhere okay so it's still so people are still typically getting fentinel through a PCA in the immediate postoperative phase fentinyl morphine okay delotted yeah yeah no the PCA uh

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 and the goal is we want to get you off an opioid even oral before you go home is that generally the stated objective of the medical system now is whatever opioids you're going to need let's try to deliver that to you in the hospital i wouldn't say necessarily because I think there are some surgeries that are going to clearly require

um prescribing an opioid after surgery remember the day 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 analesics and those analesics can be Tylenol NSAIDs if it's more than uh you know mild moderate pain it may involve an an opioid so how are you thinking about that how are you thinking about extracting the value of the opioid and minimizing the risk of long-term dependence 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 m and we've characterized we and others through research studies have characterized many of these factors so um some of these factors include uh pre-operative depression and anxiety uh higher levels of catastrophizing uh early adverse child events so a history of PTSD history of physical sexual psychological trauma all of these set up to have a higher likelihood of persistent pain and persistent opioid use now you will note um all these things I said

most of these things I said people would normally put under the psychological umbrella the key message that I want to give people and I I think I think people 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 Haw uh Ian Carol was a key player uh leader on this and we found that uh higher depression scores pre-operatively 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 use something called the Beck Depression Inventory which um standard instrument we don't use that anymore there's more modern tools i thought what was cool about this we did a factor analysis on the original paper and you can break the beck down into different components of depression anhidonia 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 your

so if you have someone who just suffers from not that anidonia is anything but unpleasant but if they're only experiencing anidonia but no self-loathing you would say well the risk isn't as high yeah you know 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 yeah especially without randomization because what you really would like to be able to see is you take a whole bunch of

people in you get their incoming metrics of anidonia dthyia self-loathing you categorize all the arms and tentacles of depression and then you randomize within each of those to with and without opioid strategies and then you I mean this is a very complicated thing to do but if you want to know the answer that's kind of the way you want to do it that's exactly it unfortunately there's not much will to do that in society these days even even in the world we live in today where we understand that for a nonzero potentially non-trivial segment of

the population the introduction to opioids that ultimately destroys people's lives is delivered by the medical system i was on the Institute of Medicine panel now the national academy uh panel called relie 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 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 um 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 datadriven studies to find

out who is at risk 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 this is a little unrelated but I remember this when I was in residency there was one of the attendings and I don't even remember who who it was but he was one of the he he had this belief he used to quote this study and I don't remember it but it said that if you injected bupivocaane into the

injection site so sorry the incision site so I'm going to I'm going to make a midline incision draw my little line inject bupivocaane so for the listener this is a long acting sodium channel blocker um wait some long period of time like 10 minutes then make the incision go about do your surgery and then immediately give that patient acetaminophen and ibuprofen immediately postoperatively and keep them on it round the clock you could eliminate opioid use and he was convinced that the only reason surgeons didn't want to do this was because nobody wants to inject and

stand there for 10 minutes with your thumb up your ass waiting for the bupivocaine to seep into the tissues and maybe it's anecdotal but it really seemed to work right like it really seemed to work that you would do this inguinal hernia repair or you know at the time some small laparottomy or what whatever it was anything and if you were willing to put that bupivocaine in and sit there and wait and I'm trying to think we might have used epi with lidocaine as well so it might have been a little epi with lidocaine plus

bupivocaine or something like that and you had to be super due diligent about keeping the acetaminophen and ibuprofen levels up any have you ever heard of anything like that so all the time yeah i mean I think he was ahead of a ahead of the curve now whether it completely eliminates any likelihood of opioids after surgery that's a little Yeah it might be strong it just reduces the requirement right i strongly believe that he was practicing good medicine and he was doing it ahead of his time now the idea of using a combination of lidocaine

and marine and epi as you well know is lidocaine short acting y so it's going to work pretty darn quick and so you can get going with your surgery while you're while the marine the bupcaine's kicking in the epi is going to not only provide hemost it's going to reduce bleeding at the site but it can keeps the local contained which means you have to use less bov which means less tissue damage like and I could be sort of mis maybe he was using epi with bupcaine I don't remember but there's something there right 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 not concept of preemptive preventative uh analesia anesthesia i think it it provides some benefit 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 mhm presumably didn't pan out it just didn't pan out yeah but look a 50% reduction in opioid requirement postoperatively would

be enormous huge absolutely and where we getting back to your your question I think we're at an interesting crux in research and clinical care where we're gathering more and more highquality data to better understand these vulnerabilities and I think we're 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 you know so that you can have an informed conversation with someone like you are at likelihood of having persistent you know opioid use because of what

you bring yeah i shared with you do patients receive that well um that's a hard discussion to have with a patient i I would imagine I guess it a little bit is about their expectations you know the challenge is when the ones who have had multiple surgeries that have been on opioids they're expecting opioids it's all about expect a lot of expectations i think the more naive person those go a little smoother um if you are professional explain to them but also allow them to make their own choices you know don't say we're not going

to give this to you yeah that makes sense um but here you are at an increased risk and that's always the discussion I have with patients whether in the acute space or particularly in the chronic space so let's talk about a couple other things that are kind of related to this but distinct um let's talk about um acupuncture what do you know about it well let's talk about through the lens of Let's talk about through the lens of chronic pain yeah yeah yeah all right clinically uh 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 jean T kong does the acupuncture she's a pain doc she does acupuncture and my view of acupuncture as a mo 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 and you say wallet biopsy because the insurance doesn't typically cover it 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 so Medicare is covering something commercial payers are not well it's possible okay yeah i historically been hard to get that uh covered so notwithstanding I like the idea of a wallet biopsy i hadn't heard that before um in your experience where do you see it being most successful what type of pain what type of clinical presentation yeah I've had some successes in back pain muscularkeeletal pain migraines headaches oddly um and it's

highly variable i studied this i had a really large program project grant to look at cortical mechanisms of this and um predictors and you know we're putting in a paper now which is a prediction model of uh real acupuncture versus placebo acupuncture uh sham how do you do place sleep acupuncture you you puncture but not in the appropriate spot well that's one option and it turns out that many of these acupuncture points overly peripheral nerves and so when you you know twiddle the needle or apply electroacupuncture are you doing a peripheral nerve stimulation i don't

know um but this is a Strideer needle that looks for all intents of purposes like an acupuncture needle it causes a little pin prick but it doesn't actually do acupuncture and it's been shown to be a good uh placebo what do I know about the mechanisms again um don't fully understand I know that there is increases in peripheral adenosine that is released with acupuncture that has an analesic effect at the primary noceptor I know that cortically in the brain there are brain systems that are modulated with acupuncture but heck if I know exactly how it

works Um there's and 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 but uh you know again uh pretty safe you know absent um some risk of infection you know make sure that the facility you're getting at uh practices good hygienic approaches pretty safe how do we think of acupuncture differing from dry needling yeah I think you need to want I think you'll want to get an a true acupuncture specialist on to because I know that

to dry that like in California I think technically you're it's not legal to dry needle but you can acupuncture i I don't even understand the difference if you're using the term dry needling from an intramuscular standpoint I don't know if that's where you're going maybe so I see acupuncture refers to just going after a nerve specifically well it's an acupuncture point okay it is a Chinese medicine list of acupuncture points i'm way out of my wheelhouse here folks um 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 it's where you get those naughty muscles yep um and you can do dry needling and what that does is it causes relaxation of the muscle acupuncture is really quite different from that next question on chronic pain what is the role of cannabis in your experience here is it is it friend or foe and again I'm sure there's a nuanced answer very nuanced this is another one where uh liable

to get some hate mail on either side of this here's what I'll tell you one the verdict is way is still way the heck out there um you look at uh well-ontrolled randomized trials most of mo there's very few of them by the way but some in neuropathic pain that show analesic benefit over a short short period of time with uh cannabis um you look at population level studies the Australia did one they did not show benefit with cannabis um 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 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 i let me let me distill it down to some talking points there's a huge number of canabonoid receptors in the human brain that are playing a role in analesia so I'm

absolutely convinced that canabonoids 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 uh they've not been well studied and they've not been studied in different groups a major part of that is because it's a schedule one drug which means that uh the DEA says that 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 that's interesting so you can't study it i would assume you couldn't study it with federal dollars because of the federal DEA uh restriction i would have assumed because it's legal in California if you were using non-federal dollars you could study it in a state like California you can study it with federal dollars nida will support funding of cannabis the regulatory controls you have to go through are crazy i see because it's schedule one

the laboratory it's it's actually more demanding it's than than how you would study cocaine we used to make jokes ucsf did some nice cannabis research and the the the word on the street was is that they would deliver the cannabis doobies in a Brinks armored truck with guys carrying M16s now I think it's got it's gotten better um but it's just been challenging to study this and I I'm firmly of the opinion we need to make here's where I'm going to upset people i firmly believe we should make it a schedule two or schedule three

drug if for no other reason to to study it with Yeah less friction what you said perfect okay there's a condition you've already alluded to today that I am sure everyone has heard of and yet if you asked most people to define it they wouldn't be able to define it and so we're going to start with what it is why someone might have it what is the prevalence are there false positives i'm talking about none other than fibromyalgia yeah yeah what was historically a garbage bag definition um fibromyalgia is um a condition of widespread bodily

pain that impacts people above and below the waist the diaphragm it's associated with um early morning stiffness fatigue mental fog uh often you know some GI problems it is uh was historically uh based on American college rheumatology definitions based on tender points and 11 out of 18 places but that's been replaced 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 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 um the cognitive aspects of it are really a problem it's also associated as I alluded to with sleep disturbances 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 what's the prevalence according to the current definition i can't tell i I should know how many millions there Pete um that's a that's a I should know how many millions and I don't what I I can tell you just to give a frame of reference um 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 um if you ask it more stringently it's 50 million if you ask it more liberally it's 100 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 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 in chronic pain and the reason why in part it's not more appreciated is because we have parcelled it out we've broken it into different categories you know 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 you know it's back

pain it's muscle skeletal 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 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 uh a disease of histrionic housewives is how they were mislabeled tragically and we're having now a greater appreciation for what it is um what's affected 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 4 kilograms per square centimeter healthy people will give a range of reporting in certain range people with fibromyalgia much much higher here's another interest I think this is an interesting um pain concept to introduce and talk about it there's something called conditioned pain modulation in the animal world we called it diffuse noxious inhibitory control or dick CPM okay think back to when you were a kid your arm hurt you walk up to your buddy you say "Hey man." You

know and he's like "How you doing?" 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 "Well the hell did you do?" By the way this is a boy only thing like I can't imagine girls did this but yes it's of course this is what little boys do 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 condition pain modulation we're all wired it is a network predominantly we think in the brain stem involving some of this uh perryqueductal gray rostal vententral medularary regions labar's first described this in the mid 80 mid70s in animals so we all do it we all have it it's this endogenous tonic inhibitory tone that you can activate when yet cause pain in another site unless you have fibromyalgia if you have fibromyalgia particularly if you're a woman

with fibromyalgia you you have impaired CPM you don't inhibit now is there a high overlap with depression anxiety and fibromyalgia and if so which is the arrow of causality yeah the chicken and we used to think that there was a high preponderance of anxiety and depression um with fibromyalgia and I think the current data doesn't support that there's any higher prevalence than uh particularly any other pain conditions i think you tend to see more of the anxiety depression broadly speaking in things like low back pain mhm i think what you see more of in fibromyalgia

is fatigue unrelenting fibro fog is what they call it and uh and then sleep disturbances and so what is the management for these patients is this a curable syndrome or is it a syndrome that is meant to be managed like HIV yes and no what do I mean well one we don't know exactly the mechanisms there's different prevailing thoughts um one thought again is it's a disruption in your central brain processing of pain through reasons unknown uh 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 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 neur neurologists typically see now but that's caused by what yeah that's the thing is this infectious what do people think is going on so fibromyalgia is frequently preceded by some event um something traumatic that traumatic can be a physical motor vehicle accident but it could also be some uh emotional or sexual abuse it

can be an infection we frequently you know also hear that story so there is some insult that people will frequently identify uh 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 dcas are the big um another one like the loxitine which is in the class of anti-depressants 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 and so we go to this a

lot uh one of the drugs that I have studied uh with Jared younger who's now at UAB is a drug called lowd dose nrexone this is a fascinating drug and it's got like this underground reputation out there that's all over the forums and 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 nrexone now trexone 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 as a treatment for addiction 50 milligrams at 4 and a half milligrams onetenth of the dose it has been shown to activate to block toll-like four receptor on the micro ga now I just introduced like this really technical concept so allow me to briefly explain the micro ga are these cells that hang around nerves but are not neurons And when I was in medical school few years several years before you what I was taught was these microgia were

like the warm fuzzy blanket that propped up the nerves i don't know what you were taught but um they provided structural support to the nerves what I learned is that was only part of the story that they're key neural immune modulators and so what I mean by that is in times of stress injury fever these microg ga 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 nrexone it blocks that it blocks that neuroinflammatory soup and in some patients

Peter this drug's been magical like magical uh I give it in four and a half milligrams silly question why not five like I 4.5 has a lot of specificity to it was there some reason why it came in at such a dose 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 microgle effect and they did it at a certain dose and so what we did is we did a milligram per kilogram convert 70 milligram 70 kilo person 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 yeah um so what are the other areas where LDN is just captivating the world complex regional pain syndrome it has had a that's a 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 lowdos nrexone um funded by the RSDSA association and

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 um or UCLA but it's in these weird neurodeenerative type conditions um where they're seeing some help now I've had some wacky really wacky patient responses if you know I mean I can share one if he is disarthric he can't speak he's got weakness he has hemibody pain burning pain this is that central pain okay salamic pain so he comes to me several years later can barely speak at all he's tried everything

let's try low dodos nrax why does he come to a pain doc cuz he's got terrible pain okay so he wasn't coming to you for the speech issue no no no he has a speech therapist it's not getting any better he's a couple few years out stroke is stabilized okay so it's this 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 but not only that he's now speaking and throwing a few words

together for the first time in like since stroke i'm like what the hell i bump up his dose you cannot hurt yourself on this drug you know I know you know this it's So I go to nine why not 10 well because it's easy to take two capsules yeah um he comes back a few months later he's now like talking in sentences and I'm like are I I I said "Are you sure this isn't due to your speech therapist?" And they swear up and down absolutely not he I go on up to like 13 and

I go up to 13 and a half and now he's having conversations and how's his pain massively better on this and um really remarkable effect i cannot the only way I can explain these things is you know in a stroke you've got like these you've got dead tissue you've got live tissue you've got these intermediate zones and somehow with reducing maybe inflammation you end up with more functional brain some somehow if that model makes sense which it at least teologically does something about that inflammatory zone in the middle between what was clearly gone and not

and not is poisoning the the part that's still okay right it's so um what is the downside of this uh meaning what would one need to be mindful of uh in in trying an approach like this the beauty of this drug is uh the only side effects that I've typically I see 20 30% of people get vivid dreams they get technicolor dreams not bad dreams not my not uh nightmares but 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 2 hours before bedtime and if it activates them a little bit take it in the morning instead so here's a silly question what's the scenario in which inflammation of the ga is a good thing 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 they got an insult activation of this neuroimmune neuroinflammatory system in a healthy state it turns off and fibromyalgia it never turned off i guess where I'm going with this is we think that at least a subset of people with neurodeenerative diseases and you mentioned multiple sclerosis but we think this is true in at least some cases of Alzheimer's disease that that neuroinflammation is a part of the pathology yeah so would there be any efficacy to a trial there in either an individual with MCI mild cognitive impairment or

as crazy as this sounds is there a reason to consider it prophylactically in high-risisk individuals with the caveat that hey by the way if you happen to get an infection like this would be a good time to stop it and ride it out and get better i think the short answer short answer is yes a little bit of the longer answer is everything I know you know this everything we do is weighing risk and benefits y this is one drug I am hardressed to come up with significant risks we ha we have decades and decades

and decades of experience with this drug in people with addiction at 10x the dose at 10x and how long are they typically on that drug lifetime so meaning for for a subset of individuals just putting them on the party dose of 50 milligrams of Nraxone keeps them free of alcohol and opioids for life because it so blunts the pleasure center yeah the the problem is as all the addictionologists know is that um it's hard to keep people on this because they can just stop it and go back and use you know so that's why you've

got No you have to want to be off you have to want to be off they have injectable uh versions of this is it not called Vivitrol is it it's it's an injectable uh under the skin that lasts x number of days months um but yeah we've got a lot of long-term data on this and from a pilot standpoint with informed consent obviously and just you know I would view that as a kind of a novel treatment in patients that one could try out monitor um do some objective measures and uh see what what see

what you get um I wouldn't say that I 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 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 oh you the reason is you can't go

to Safeway or Costco and get this you can't get lowd dose nrexrax on there you mean you have to it has to be compounded at 4.5 you're saying you're right okay 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 um you can probably find it in your local area at other compoundingies it usually runs about $30 a month so it's basically a free drug insurance doesn't often cover it because it's experiment they

consider it experimental but it's basically a free drug so it's a buck a day yeah yeah so I uh it 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 yeah my my my wheels are turning on I'm very curious to see if anybody has looked at LDN and um and and and in in in any of the neuroinflammation stuff because look we we you know we see the relationship between herpes simplex virus and uh Alzheimer's disease uh between shingles especially ocular

variants of it and Alzheimer's disease we know that there is some relationship between inflammation and this disease and and we know that that's obviously not all paths cross through that right there are there are lipid mediated paths metabolic paths vascular paths but I think you know it would be very difficult to make the case there's not an inflammatory path towards that condition and so interesting to think about it is and I need you to you know just as a ideally a good scientist tell you that not everybody buys in to the micro gal model that

I'm describing there are um friends and colleagues at Michigan uh Dan Claw brilliant brilliant guy who is uh very much in disagreement with me who believes that even at these low doses you're antagonizing the operic system and in essence kind of resetting it in these chronic pain states so that you're normalizing the endogenous tone and you know what he could that's the fun thing about science and why we try to keep our egos out of it the truth will come forward what's the evidence for the inhibition of the the toll-like receptor is that is that

in is that in in vitro yeah and here's the thing yeah it is in vitro uh 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 even you know we 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 uh ulcerative colitis I believe is another one uh and these weird neurodeenerative things I have a hard time understanding why mild

antagonism of opioids is going to have an impact on those conditions and why do you think you see I mean that's an interesting one well it's another one of these weird uh degenerative but through a central effect h 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 uh I will have to go and look just for kicks when I get back the hotel room and just see about the whole mild cognitive impairment Alzheimer's aspects

of it i clearly don't treat these patients but it is an intriguing idea isn't it isn't it so when we met 25 years ago how big was the department at Stanford in pain division oh we had uh about 10 to 12 people in it this is all the physicians the 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 we one of

the top in NIH fund it's really come a long way it's been really exciting to see the growth and and the careers and the people we've helped out so I'll I'll finish the story of of how we met so I'm in this state of um total hell um in addition to all the stuff I mentioned about you know this incredible pain i couldn't even stand up literally couldn't stand um and if I did I had to be hunched over and so at the time I was dating an anesthesiology resident uh and she was the one

that said "Hey we just need to get you in this pain clinic like we just we just got to we got to break some stuff like this is this is going nowhere you're circling the drain here kid." And so I think she was at the time doing her she was in her last year of anesthesiology so I think she was doing a rotation through pain maybe that's that's that's probably how you know she she weasled me in there so I come and see you in clinic by the way at this point my mom had flown

down from Toronto to take care of me it's not like I could drive or do anything right so my mom drives me into the hospital come in and see you you hear the story we'd ruled out anything that required any more surgical intervention in other words I'd undergone another MRI i'd had a flexion extension film it it I wasn't surgically unstable um and in fact where the original injury was didn't even seem to be what was driving the pain now so you said "Look the first thing we're going to do is we're going to give

you an IV lidocaine drip to see if we can just calm these sodium channels down." Did it do anything so you said "Well how much do you weigh?" I said "I weigh 80 kilos." You said "Okay we're going to give you 400 milligrams of lidocaine introvenously." And I said "Dr mackey I just took my boards a year ago that's a toxic dose he said "Don't worry we're going to do it in a cardiac monitored room you will be on an EKG and we will be able to defibrillate you if you have an arrhythmia." So I

said "Go for it." So in 20 minutes I got 400 milligrams of lidocaine didn't touch the pain did tried something else didn't touch the pain by now it was 8:00 at night oh wow and you said "Okay the only thing left to do at this point is to go in there and do a series of injections at every single facet joint every single dorsal root uh every nerve root every dorsal root ganglia the entire length of your spine I will not be able to diagnose what is wrong because I'm basically going to stop all the

pain but then we will chip away at this over the coming months." And I said "Great can we do it now?" You said "No it's 8:00 at night we don't have an anesthesiologist i'm the only one here." I said "You're an anesthesiologist." You said "Yes but I'm the one that's doing the procedure." So I said "Well why can't we do that?" And then you said "Well we won't be able to give you any sedation and I'm about to stick 45 needles in your back." And I said "I don't care that's how much pain I am

in right now." Yeah so we go into the O and you proceeded to put I think you know hydrocortisone you know bivocaine and you lit me up up and down the back and two hours later I stood up for the first time in 3 months i was completely pain-free this was remarkable so we get home it's midnight i say to my mom "I'm not going to bed i'm gonna go for a walk because like I hadn't walked in three months and you know the campus loop of Stanford very well around it yes yeah i walked

it until the morning it's a fourmile loop it's Yeah i just walked around and around and around till 9:00 in the morning came back home went on to develop uh planner fasciitis because when you don't walk for three months and then you don't stop walking but put that aside and you told me "Look you're going to probably feel okay for a few days and then the pain is going to come back." Well it actually turned out to be 2 weeks that I was painfree and then the pain came back and over the next 3 or

4 months you repeated comparable procedures but with more and more precision i.e narrowing in at what the problem was and if my memory serves me correctly it was mostly in the T12 L1 area those and and I think the ultimate diagnosis was look you lost so much disc space at L5S1 through the multiple surgeries if you look at my MRI today I basically don't have a disc at L5S1 that you've now developed this facet arthropathy that far up and that's where those nerve roots are going into kidneys and testes um but what was amazing was

these injections allowed me to go and do rehab which I took on like a vengeance and basically rebuilt the strength in the musculature of my back and so within 9 months I was like back to nine months of meeting you a year of the injury like I was I was functional um within two years I I could I could get to the point where I forgot about it for days at a time like I give you an example i could actually sneeze without bracing wow that was something I couldn't do yeah for a year I

couldn't lean over the sink to brush my teeth that's how weak I'd become like you know just the just the moment arm of your torso leaning over i couldn't do that i had to fully brace and support myself to just brush my teeth so you asked like what was the lasting impact of that well one of and I've told this story many times and of course my kids know it well one of the lasting impacts was my absolute love for parking as far as possible from wherever I'm going because when I was going through this

they wanted to give me a wheelchair parking thing and I was like I don't want it you know it was just a psychological thing i was like I don't want it i don't care how far I have to walk and so now you know my kids know you sort of celebrate your legs by parking far um and and in many ways that became part of this idea this thesis I had of this centinary decathlon this idea of like what are you training for you're training for life life is your sport and that can be something

as mundane as being able to walk to the grocery store if you park if there's no spot near where you need to go and can you push the cart to the car and all that kind of stuff so the net net for me is it has been incredibly positive um again I'm incredibly grateful Sean to you because again had I not been at Stanford had I not had you know that girlfriend who I won't name her to embarrass her uh although I think she's still on the faculty at Stanford by the way um you know

I I just think there's a lot of ways that story could have gone sideways so I so I feel incredibly grateful and the final part of the gratitude is that I would go on to Hopkins for my residency in an in an emergency room that serviced some of the most opioid addicted people on the planet um and based on my own experience with that I can say I always had a sense of humility about what they were going through i always looked at it as "Oh God I I I feel your pain that is awful."

And I and I could have been there wow but by the grace so that's that's been my experience with it which is 90% good that's a great story you know I Peter I uh I listen to that and in one hand I remember it and another hand it's been so 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 you know late at night and just try to take control of the

situ yeah just put the fire out just spray the hose yeah because normally to be clear to the audience I would never approach that in a chronic situation like that uh 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 so let me ask you a question Sean um how common or uncommon is my story because when when you meet a person like me is there a part of you that thinks we're never going to fix this guy like

this guy is going to this guy's life is over he's on 320 milligrams of oxy he's hasn't walked in months he's in so much pain the lethal dose of lidocaine did nothing is there a part of you that thinks this is a this is this is a chronic pain patient this is a guy who's going to be in chronic pain the rest of his life or do you look at a guy like that and say "No no we can fix this." What I usually look at I 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 and every once in a while we can cure just eliminate make it go away never comes back like my case like your case which honestly I didn't even know about until recently i was lost to followup lost a followup i'll tell you maybe in just a little bit like how I did find out and um yeah um I you know why I 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 you know I I've never hit a point in my career with a patient where I've ever said "We're done." Like I got nothing i got nothing you know it's 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 new kid on the block opioids NSAIDs um some tricyclic but that was about it and by the way that also that notion contributed to the opioid crisis because we didn't have tools

now there's over 200 medications that have shown to have analesic properties we have over 200 procedures that we do for pain scores of mindbody therapies scores of complimentary alternative therapies and physical and rehabilitative approaches like the toolbox that we can draw upon is so much larger often the problem is not with all the tools we have 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 in the acute setting it's free it is often it's eliminating pain because in an acute perioperative or acute injury situation you just want you you need to eliminate or significantly reduce it before you can get people moving which was kind of in your case um yeah I I I got to tell you I was I was tempted because I I my memory of this was a little vague i almost I for a moment I thought maybe I just look up my records on Epic and just see what's what and I'm like

"No man that's what gets you fired." Uh and so I didn't um I thought I I'm glad you filled in the the the memory gaps and I'm just I'm literally just so happy for you um can I ask you some questions about it all sure and kind of maybe build on some of the things we've been talking about so to what degree so one of So some of the stuff that's going on when you were in this is you were in distress clearly there was a lot of um 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 uh neologisms so he created uh catastrophizing he created the word awalizing awfulizing didn't stick around um catastrophizing was not related to pain but got used for pain has three factors to it uh amplification of pain rumination or repetitive thoughts about pain and a sense of helplessness or loss of control over your pain check check check yeah it's natural there's nothing like people we got

a lot of controversy in the field on this term because it has such a porative impact and unfortunately some of the docs have weaponized it against patient oh you're a catastrophizer tragic but it has real neurobbiiologic 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 systems so that they can no longer downregulate your pain they have abnormal connections to uh hypothalamic regions which are key in hypothalamic pituitary adrenal axis your HPA axis which I know you're very

familiar with and so what you you know in an acute situation you get a release of cortisol for you know for stress response you know this is a surgeon it's great it keeps us alive chronically terrible and so you get this alossteric alostatic 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 like I used the interventions the procedures

to help break an immediate cycle to get you on a path we do this with other patients similarly and then it's learning skills yeah that's the very important point that I think shouldn't be lost on this which is the the psy breaking the cycle isn't the cure it sets you up to go after the cure i mean I had to go through two hours a day of rehab for six months yeah wow i mean I had to learn how to move again correctly i had to strengthen the muscles that were going to make up for

doing what my spine would no longer do but you couldn't do that if you were in pain so you had to learn to do that and you had to be at least pain-free enough to do it but not push yourself too hard that you would reactivate the injury like there was a there was a balancing act but then you know and you had to be able to sleep all these things and you had to be able to clear your mind and get out of that catastrophizing loop 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 in the edited but when I read that story who of this woman who shoulder injury and then went down this bad path yep can't golf can't garden can't do anything all I 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 uh social functioning so we call pain a biocschosocial 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 so you know my guess is she invariably withdrew she became deconditioned 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 that we need to manage your sleep we need to manage all the things you put beautifully in your book but I think be we we we also need to help them better manage their pain so that they can have the function and

do all the things that you you say so nicely in your book i don't know whether what your thoughts are actually I was going to say that um I was somewhere recently where I was asked to define health span and health span is squishy to define because there's like a medical definition that I've repeatedly said I think is insufficient right so the medical definition of health span is the period of time in which you're free of disability and disease so not very helpful um and I prefer a more functional version of health span and unfortunately

it's too long for me to rattle off but one of the lines is freedom from pain so that's you know just as it's important to have strength stability um aerobic efficiency peak aerobic output explosiveness i mean all of these things are going to reduce as you age but the longer you preserve them the better but one of them is freedom from pain yeah yeah you know the data on elderly people who get a hip fracture and then it's an like spiral immediately downhill to death yeah the listeners of this podcast are not uh they're not

strangers to those statistics and I'm sorry if I'm repeating things no no no but that particular one is so I mean it's it's so tragic yeah and I just keep thinking if we could better help get their pain under control and address them from that holistic you know that 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 I hope it will um yeah you know when you went through all of this you you get through the rehab like 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 yeah and it's actually been yet another benefit of this experience is the ability I now have to help my patients so if you just look at the population and understand the ubiquity and frequency of lower back pain and you realize I don't remember the numbers but like let's say a third of people are going to go through some bout of lower back pain in their life um a number of

my patients have also been in the loop of chronic lower back pain right and for these patients one of the most powerful messages I can deliver to them is learning that a setback is not permanent so part of the journey because remember it's not like in the nine months after this injury got better I never had another setback no within that period of time I would have days where I felt bad again now fortunately I never went back to laying on the floor for days that I never experienced that level of discomfort again but there

were many days when I was very uncomfortable and it would wax and wayne but over time and with every time that I would recover from one of those cycles my confidence would go up yeah the ability to know that this is going to pass and I'm going to have to make some adjustments yeah and I'm going to have to not sit and I'm going to have to change the way I lay and I'm going to have to do these exercises a little bit more that's okay this will pass and so I actually just got an

email from a former patient he's not even my patient anymore and he said to me "Hey Peter just want to let you know man I have never forgotten what you said about this and I just had a big setback last week and this would have normally taken me down the spiral to hell and I hear your words telling me "It's okay this will pass." And he's like "You know what it's a week later I'm already on the mend." So there's no difference between the phys it's not impacting physiology right it's impacting the psychology and the

psychology is what goes on to impact the physiology so so again I think of that as I tell patients this is not going to be a monotonic improvement right it's going to look more like the S&P 500 where if you step back 30 years yes it's monotonically going up look at it for a given week not at all yeah can go down it's it's quite volatile now the volatility will decrease over time but it never goes to zero yeah that's a great great story and clearly you've it's helped you be a better doc and uh

help people you know I listen to your story and everybody's story obviously is very different and personal uh I have my own variant of this and you know I uh I don't talk about this much because I I tend to be a little private with these things but um I suffer from cluster headaches and all my life as far as I can remember I would get these headaches 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 I'd be in just terrible the most insane pain I've ever had i've broken a lot of bones in sports nothing like trivial compared to that and nothing I would do would work uh I'd occasionally go to the emergency department and they'd say it's a sinus headache and they give me antihistamines and they'd prescribe them and sure enough they worked because it always went away in a couple weeks right um I remember um in residency getting one of these in the midst of a cardiac anesthesia rotation

and barely able to get the patient to the uh recovery room and I just went into a call room and I just hung out the the the thing and and 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 I thought I had a brain tumor i was convinced and I I thought this was going to kill me um and you get really scared that it's never going away you I catastrophized after the end of like a couple weeks i'm like this

is never 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 I got cluster headaches and how are they treated now well um first of all just just to let people know what a cluster headache is it it typically manifests as uh headaches that last anywhere from uh you know upwards of a of a couple hours they can occur uh eight times a day to you know every other day um they tend to have these weird characteristics with

uh they're under a class of trigeminal autonomic syphalgia fancy term for simply meaning that you get eye tearing redness in your eye 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 uh you know Beth and you know would say well you know do 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 um

so what I did you know in the period of all this fear I learned every damn thing I can learn about cluster headaches every single thing what how many people get these what percent of the population it's a rare 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 but less prevalent than migraines okay yeah less prevalent than migraines common treatments for these um there's there's abortive and there is preventative and what the preventative

are like uh calcium channel blockers uh that you you can take uh abortive is you know the typical migraine medications the tripans so I have stockpiles of you know tripans uh high flow oxygen so you know I knew I was getting one of these before these happen I get this prodal phase with weird appetite sleep gets disrupted I know and a sticky eye sensation and 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

and that'll rescue it now 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 h 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 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 a fearful like I was having a subacoid bleed right 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 and that gives you control so when these happen uh 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

and that's you know 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 uh putting that to use and and ideally giving yourself a degree of self self-efficacy over your health and when I listened to your story it it it had parallels there in that uh that journey that you had and you you've clearly used it and maybe trite to say make you a better person but yeah and and yeah I have a lot of empathy for uh people as a consequence

well Sean this has been this has been a great discussion um I think we're we're we're certainly better off today as a species having a medical um discipline that is devoted to pain we have the luxury of caring about this now right you know there was a time when just not dying was the highest priority and now it's it's we need more than that it's not just that we don't want to die it's that we want to be able to live painf free um not to be confused with discomfort free i'm still a big proponent

of discomfort as I'm sure are you we we should be out there you know working out hard experiencing discomfort um but but chronic pain can be inflammatory to the psyche um and it's not something I would wish on anybody so um it's great to know that that since my time as a patient there that department has increased logfold and I hope that's true and trust that it's true around the country so thanks for the work you're doing thank you Peter i uh you know it's been 20 some odd years since we've seen each other and

if I can just say that uh I remember when I I saw you you were kind of an intense guy and I've mellowed have you i've mellowed since then 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 and he's like you know Dad uh 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 it's like I had no idea uh that he's done so well for himself and uh and and and you have you know you are 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 Atas we need you like delivering these messages that are empowering people because you're you're making a big impact out there and I just appreciate you inviting me on to spend some time

with you so thank you thanks Sean [Music]