Dr. Sean Mackey: Tools to Reduce & Manage Pain

welcome to the huberman Lab podcast

where we discuss science and

science-based tools for everyday

[Music]

life I'm Andrew huberman and I'm a

professor of neurobiology and

Opthalmology at Stanford School of

Medicine my guest today is Dr Shawn

Mackey Dr Shawn Mackey is a medical

doctor that is he treats patients as

well as a PhD meaning he runs a

laboratory he is the chief of the

division of pain medicine and a

professor of both anesthesiology and

neurology at Stanford University School

of Medicine today we discuss what is

pain most of us are familiar with the

notion of pain from having a physical

injury or some sort of chronic pain or a

headache today Dr Macky makes clear what

the origins of pain are both in the

nervous system and outside the nervous

system that is the interactions between

the brain and the body that give rise to

this thing that we call pain indeed we

discussed the critical link between

physical pain and emotional pain and how

altering one's perception of emotional

or physical pain can often change the

other we also discuss some of the

changes in the nervous system that occur

when we experience pain and how that can

give rise to chronic pain we also of

course cover different methods to reduce

pain safely and those methods include

behavioral tools psychological tools

nutrition supplementation and of course

prescription drugs we discussed the

intimate relationship between

temperature that is heat and cold and

pain and Pain Relief so if you're

interested in the use of heat or cold to

modulate pain that conversation ought to

be of interest as well we also touch on

some highly controversial topics such as

opioids opioids are a substance that

your body naturally makes but of course

many people are familiar with exogenous

opioids that is opioids that are

available as drugs and the so-called

opioid crisis Dr Mai makes very clear

which specific clinical circumstances

weren't the use of exogenous opioids

with of of course a warning about their

potent addictive potential and we get

into a bit of discussion about where the

opioid crisis and the use of opioid

drugs to control pain is and is going

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huberman and now for my discussion with

Dr Shawn Mackey Dr Mackey welcome oh

it's a pleasure to be here thank you

this is a long time coming we're

colleagues at Stanford and I'm familiar

with your work but today we're going to

take a pretty Broad and deep survey of

this thing called pain so I'll just

start off very simply and ask what is

pain pain is this complex and subjective

experience that serves a crucial role

for all of us to keep us away from

injury or

harm it is both a sensory and an

emotional experience and I think that

gets lost on people that includes this

emotional component to it and it is

incredibly individual and we'll get more

into that hopefully as time goes by that

you know your pain is different from my

pain and is different from everybody

else's it takes an incredible toll on

society when it goes chronic when it

becomes persistent to the tune of about

a 100 million Americans and at last

count about a half a trillion dollars a

year in medical expenses uh so an

astounding problem we're facing in

society and one that's only getting

worse and I'm hoping during the course

of this discussion that we can kind of

break down a little bit of the

foundation of pain and kind of build it

back up because

unfortunately uh in society there's a

lot of misunderstanding about what pain

is and I think uh hopefully we can build

that foundation and then layer on some

some useful treatments and useful

options for people I'm glad you pointed

out this link between the sensory and

the emotional experience every once in a

while I'll pull something or I'll have

like you know like a kink in my neck or

my back and fortunately for me it

resolves pretty quickly but I notice

that when I'm experiencing that kind of

pain that I become slightly more

irritable perhaps much more irritable

depending on who you ask and that

everything becomes more challenging

thinking is harder sleeping is harder

concentrating on anything besides pain

it's it's a um it's as if something's

nagging from the inside and so that

raises the the next question that I have

which is

is pain something that's in our brain in

our body or both it's clearly in our

brain and can I take a moment to kind of

lay a little foundation for some of that

to help clear up some of the mystery of

pain we know that pain most pain all

starts with some stimulus whether it be

that kink in your neck or your shoulder

from working out or turning the wrong

way and what's going on there uh in your

body is not pain what's going on is that

uh there are sensors in our skin our

soft tissue our deep tissues called

noors and these noors are sensing

elements and they sense different types

of stimuli they can sense temperature uh

heat cold they sense pressure they can

sense pH changes due to for instance

inflammation that may occur from uh any

something going on in your neck or your

shoulder those signals up nerve fiber

types and the two that we we refer to

are a Delta and C fibers one transmits

very fast it's responsible that you know

sharp jolt of pain that goes to your

brain when we uh you know step on a tack

or put our hand on a hot stove and

there's another fiber called a CA fiber

which is much slower and responsible for

that dull achy pain now these signals

they go to the spinal cord lie up and

down our uh from our head down to our

back and they're they're shaped they're

changed a little

bit they then are sent up to the brain

and it's once they hit the brain and

they converge with this Magical Mystery

set of nerves in the brain that it

becomes the experience of pain and if

there's one key message I'd like to get

to the audience is that what goes on out

here what goes on in your shoulder in

your neck is not pain that's no

susception those are

electrical signals electrochemical

impulses being transmitted and that is

to be distinguished from what becomes

the subjective experience of pain that

you have and why it's

critical is that our brain serves so

many functions of emotions cognitions uh

memory action all of that shapes those

signals coming in from our body to

create your unique experience of pain

that's different from everybody

else's and I think that's important to

note

because we are frequently left with this

notion of this

onetoone concordance between the

stimulus and the experience of pain you

know Renee Dart that French uh

philosopher I think 17th

century um was the one who first

postulated this idea of this direct

linkage between the body and our actions

and the stimulus and the response and

it's wrong and unfortunately even in

medical care we have this biomedical

model that still is perpetuating this

idea of a onetoone

relationship and that's a critically

important point to get

across in large part because frequently

as humans we tend to project onto others

our own experiences of pain and when we

see somebody who's got an injury or

something else going on we immediately

put that on them and that has also been

a problem uh with many people suffering

in chronic pain which is often viewed as

the invisible disease so when you say we

put that on them you mean when somebody

reports being in pain we have a hard

time understanding what they're are

experiencing because it's going to be

very different than the way that we

experience pain conversely if somebody's

in pain they tend to assume that people

are experiencing pain the way that they

are do I have that right you have it

perfectly right and it actually if I can

build on that gets worse because

sometimes you have conditions like

fibromyalgia that maybe we'll get into

where outwardly visibly you don't see

anything wrong we're used to thinking of

pain as a fractured you know bone as a

swollen ankle we see that and then we

like okay well you've got pain you got

legitimate pain whereas this invisible

disease of chronic pain frequently you

don't have something outwardly that

you're seeing but we bring in our own

history of pain and we put that on other

people I have a question that's somewhat

mechanistic but we'll keep it accessible

to anybody regardless of their

background so you mentioned the NOS

acceptors are in the body and everywhere

in the body and on the surface of the

body to be able to detect certain kinds

of stimula and then those signals are

sent up into the brain and the Brain

creates this subjective experience that

we call pain is there a dedicated set of

areas in the brain that that are

something akin to like a pain pathway

and the reason I ask this is that for

you know for vision for hearing for

touch we probably all experience those

somewhat differently your perception of

red is probably a little different than

my perception of red we don't know for

sure but experiments support that idea

but there's a major difference between

people experiencing the same thing

differently according to like a

mysterious mechanism in the brain as

opposed to like a an area in the brain

that we can look and say like hey like

like that's where pain is uh represented

that's where all these these inputs from

the body are put together to create this

thing that we call pain um like is there

an area of the the thalamus a structure

in the middle of the brain that takes

incoming sensory information that we

could say oh that's the pain pathway is

there a part of our neocortex the outer

shell of the the brain more or less um

beneath the skull but nonetheless on the

outer portion of the human brain that we

could say oh that's where pain exists or

is it a distributed phenomenon yeah

that's a great question and you know

because we'd all love if there was a

pain center in the brain that we could

just go knock out but it's not that

simple and in part because pain is such

a conserved phenomenon it it is there it

is so wonderful because it is so

terrible unless it goes wrong

but when you knock out one pathway going

to the brain there's others there that

will carry that system forward and

you'll still experience pain and it's

there to keep us all alive now to get to

your point no there's not one pain brain

area it is thought to be more of a

distributed network of different brain

systems we at one point in time called

it the pain Matrix which represented

areas such as uh the insular cortex the

singulate

cortex the amydala a number of these

brain regions that all subserve

different functions we moving away from

that because it seems like every year or

so we pick up another region of the

brain that's contributing to this

network that subserves some additional

function some nuanced layer to

it that

said we have been able to identify some

common signatures common brain networks

that seem to represent the experience of

pain and this is where the development

of brain-based biomarkers has come in

and this is some of the work that I've

done

starting gosh well over a dozen years

ago and uh others have been building on

and what we're finding is that there

does seem to be this this conserved

region set of uh distributed regions

that do represent the experience of pain

so when somebody takes a so-called

painkiller let let's take a uh typical

over-the-counter painkiller like a

ibuprofen or camenen to uh lessen pain

of some kind yeah where is that drug or

drugs acting is it in the body or is it

at the level of the brain or both yeah

and this is where some of the challenges

we get into with language because

technically nids nonsteroidal

anti-inflammatory drugs like ibuprofen

like

Naperson they're actually not analgesics

they're not technically pain killers so

an analgesic is the descriptor for a

quote unquote painkiller yeah there that

would be more correct like an opioid

would be would fit into that category

the N heads are anti-inflammatory drugs

they're also there's another this is a

technical term they're

anti-hyperalgesic drugs and

so one of the things that happens after

an injury is that we get

sensitization of the area that's injured

and it's a beautiful thing because it

sends a message to us to protect it um

what the end heads do is they reduce

some of that sensitization out in the

periphery and then back in the spinal

cord and in the brain but they don't

actually so for instance I was going to

say try this at home but probably not

you can um in a normal situation you

know hit your hand with a fork measure

the amount of pain I'll go take an NSAID

like ibuprofen if you hit your hand with

that same Fork there'll be no difference

folks please don't do that don't do that

at home please yeah or any or anywhere

for that matter or anywhere for that

matter but you're describing pain and

the local inflammation response and the

hyper Alesia the increase in pain in

that general area as something very

adaptive very important so it raises the

question what is the threshold for

saying that somebody should treat their

pain reduce their pain I mean you know

anytime I've done um you know surgeries

on animals which I don't do anymore in

the laboratory but we used to you know

you would give them painkillers

post-operatively I've had iies before I

had painkillers postoperatively although

I don't like taking them I don't like

the way they make my brain feel and so

uh but we of course know that if you

increase the dose of any pain medication

too much then that animal or a human can

potentially injure themselves worse or

not protect that injured area so it

raises a whole set of sort of medical

ethical but also just purely biological

questions how do you set the threshold

for yes blunt pain versus no allow the

pain to be there as an adaptive way of

protecting yourself in healing

presumably the inflammation is part of

the healing process too and as you

mentioned before pain is so subjective

and it's different between all of us I

mean how do we decide uh whether or not

it's a good or bad idea to blunt that

pain yeah I think the the the threshold

is when it's impacting your quality of

life and your ability to take care of

activities at daily living engage with

family friends go to work

and that that s kind of a your your

threshold for you know whether it's

reasonable to to take a medication or

not it's a lot of controversy in the

space right now it used to be we all

recommended just Neds for any type of

acute injury I is non-steroid

anti-inflammatory drugs indeed could

could we maybe list off a few of those

so I mentioned ibuprofen aceto Menin so

sometimes referred to as you know the

classic Advil Tylenol we won't throw out

name brands there but what are some

others Naproxin neoen is another one

Toral or ketorolac is another one the

two over-the-counter nids the

prototypical over-the-counter ones are

ibuprofen and napasin those are the ones

you can buy over the counter without a

prescription uh Tylenol actually has a

slightly different mechanism of injury

but you know still fits in that same

general class it tends to be more

centrally acting IBU uh Tylenol or

camenen but take we say centrally you

mean Brain Brain Brain thank you than

you and uh is aspirin considered an

insat I don't believe as would fit into

that category of basically a Cox cyc

oxygenase inhibitor this is one of the

the chemical mediators that gets

released during injury and that chemical

uh substance has a tendency to wind up

or amplify the

noors so that after an injury you note

that you're more sensitive there after a

sunburn you end up having more

sensitization that is what we refer to

as peripheral sensitization because it's

out in the periphery we're winding up or

amplifying the

response uh aspirin n heads in general

will reduce that inflammation they're

anti- um

hyperalgesic and uh pardon again the

jargony terms that we use but hope

coming across along as we go but but you

know to your point you don't want to for

instance let's imagine you have a

fractured ankle

you don't want to be reaching for a very

potent

opioid just so that you can continue

walking on a fractured ankle that you

haven't gotten evaluated by a clinician

and perhaps casted that wouldn't be safe

those are rather extreme examples you

know we get into those debates right in

professional sports where you know they

they send the person back out on the

field with a broken bone you know having

given them an ejection or something I'm

I'm hoping that doesn't go on anymore

but uh I'm sure it goes on okay yeah

well there's all sorts of other things I

get contacted all the time professional

teams and athletes asking how they can

get back in quicker nowadays the big

thing are these uh peptides that can

certainly accelerate healing people are

traveling out of country get stem cell

injections all with all with uh very few

randomized control trials but I assure

you that um Courtside and in the locker

room mainly in the locker room their

corticosteroid injections their

painkiller injections I mean it's it's

not at any expense but it's not far from

that okay yeah yeah well you know when

you're you're making millions of dollars

a year and I I get the being back on the

field but for the rest of us mere

mortals um I think that's where we would

want to draw a line get medical

attention if you've got an acute injury

going a little bit deeper into mechanism

because I think it's going to serve us

well now and going forward you mentioned

the IDS and um this uh Cox Cox is one of

it's a is it in the family of PR gland

can we talk about prandin because I

think there are a lot of people nowadays

we hear about inflammation yeah you know

inflammation's bad inflammation's bad

but you know one of the things that we

talk about a lot on this podcast is the

fact that you know cortisol isn't bad

inflammation isn't bad these things

serve an important biological role so

the prostaglandins seem to be one of the

main ways that our immune system uh

responds to a physical or chemical

injury and and creates inflammation and

that as you said that inflammation

sensitizes an area makes it literally

more sensitive and then we introduce

these drugs that um to restore normal

functioning and living could we

establish like what normal functioning

is I mean for instance if we make this

really concrete could we say well if you

can sleep fall asleep at night and stay

asleep or perhaps go back to sleep after

you've woken up in the middle of the

night then will you heal during sleep

and so you know take as little

painkiller as possible but enough that

still still lets you sleep well at night

is that it's sort of normal functioning

because when I have a kink in my neck I

don't want to do much of anything I try

but it's really frustrating so what is I

mean as a physician how and as a patient

how do we determine normal functioning

yeah and you're getting into the Nuance

the complexity of this problem because

we've been talking about NSAIDs the IB

prence and

napins and as I said early on we used to

just give these out all the time but

then the research comes out and shows

that by blocking inflammation by

blocking that we may be blocking the

normal healing process and so we've seen

delays in fracture repair we've been

seeing delays in tissue repair and so

now you've got on one hand a medication

that may help with pain help you improve

function you've got on the other hand

something you're taking that may delay

the process where do you draw the line

as a physician my Approach is really

basically what you said it's balancing

the fact that if you're not sleeping at

night you're not going to heal and

you're not going to be able to do what

you need to do the next day and if

taking an inset helps you sleep and

helps you uh engage with what you need

to do take it at the lowest dose that

you can get away

with I've heard before that NAD should

be taken no more than once every six

hours people will alternate different

types of ins

that's usually try reduce fever another

situation where an Adaptive response

fever you know people go out of their

way to block it right prevent the brain

from cooking but again opens up the same

set of issues and so I'm wondering if

somebody has some pain that makes you

know moving about frustrating and it's

and it's difficult but you know they can

sleep at night reasonably well maybe not

as well as they normally do would your

suggestion to that person if their goal

is to heal as quickly as possible to

just not take anything yeah so we've got

a lot more data on the benefits of nids

this class of medication reducing pain

then we have data uh showing the bad

consequences of it and so we're still

needing more data on the whole healing

message I think that a lot of the

orthopedic surgeons out there prefer

people not to be on IDs after for

instance a total hip replacement at

total knee replacement because I think

that's pretty clear but that's not what

we're talking about right now so so one

of the other interesting things about n

heads like we mentioned ibuprofin and

aprin huge individual variability around

those so personally ibuprofen is not

very effective for me napasin is for

others it may be just exactly the

opposite so there's value in rotating

them and finding out which works best

for your particular situation you

mentioned the timing of it ibuprofen is

typically given no more than three times

a a day it's got a short halflife

Naperson twice a day what's critical I

need to give this message is in both

situations make sure that you have food

in your stomach make sure you're not

taking it on an empty stomach make sure

you're drinking plenty of fluids and if

you've got any um GI issues if you've

got any bleeding issues if you've got

kidney issues if you've got heart issues

talk to your doc talk to your clinician

before you embark on this because these

medications do have side effects and

adverse consequences in vulnerable

people and what about aspirin I've heard

that aspirin can benefit heart health so

I take a baby aspirin every day and if I

have a pain that is just too intense for

normal functioning as we're defining it

then I'll increase that um dose of

aspirin and I just assume aspirin is the

healthiest and sad for me because well

it's also good for heart health and it's

killing pain in those instances as

opposed to taking anything else is my

logic flawed and if it is feel free to

tell me no for for you your logic is

perfect and that's where it gets to the

individual person and for a lot of

people that model would work as well so

baby asper in 81 milligrams a day acts

as an antiplatelet agent it helps you

know here even though we're getting

controversy over the role of baby

aspirin if you dive into the current

literature even baby aspirin is

controversial even baby aspirin these

days and now what they're doing with

with the data is defining age ranges

when they say baby aspirin yes baby

aspirin no and so you know we're

learning a lot more about that I still

take a baby aspirin every day yeah I

take a baby aspirin you get to the

higher dose is say four times as much up

around 325 milligrams or so it's now an

anti-inflammatory it's now acting more

like the ibuprofen and the

napasin so um different mechanisms of

action at different

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huberman I promise we won't go into

every medication in such detail but but

these are the most commonly used

over-the-counter treatments for pain as

far as I know know um are there any um

issues with you know people who drink

caffeine who then are taking these drugs

are like what are some of the uh the uh

interactions that these things can have

as far as I know caffeine actually

touches into the prostag gland in

pathway doesn't it yes and that's where

you know caffeine can be used

effectively for headaches for migraines

and uh it can help potentiate the

analgesic response uh some people get uh

stomach irritation though with caffeine

so just again mind that you take an nsid

with uh a lot of coffee uh have some

food in your stomach you know you

brought up earlier aeta menen or Tylenol

Tylenol doesn't have the same side

effect or adverse event profile that the

Nets do so Tylenol is safe on the

stomach um where you need to be careful

about Tylenol is not to exceed 4,000

milligrams or four grams per day in

divided

doses so two extra strength Tylenol done

four times a day for many people is safe

some say two grams some say four grams

the key here is around your liver so if

you've got good liver function if you're

not abusing alcohol that's a general

rule of thumb that you can use for

Tylenol um but it's not going to upset

your stomach there are versions of the

NSAIDs that we refer to as Cox 2

inhibitor they're very selective like

celic coxib that is uh less irritating

on the stomach that's by prescription

only though but you can think of it as

working very much the same as the

napasin and the ibuprofen so talk with

your clinician you know to to try to

tease those apart if you have problems

in your stomach with the NSAIDs and

they're really effective for you you can

be given other types of medications that

help block or reduce the GI issues

associated with the

insets very useful information thank you

here we're talking about chemical

interventions to the pain

process what about mechanical

interventions so I was taught in my

basic Neuroscience about I think it's

melzack and walls gate theory of pain do

I have this right where you know we all

have this instinctual response animals

have it too right if they uh you bump

your knee or your toe that you grab and

you rub it and that that rubbing

response is actually contributing to the

activation of a neural pathway that does

indeed reduce the pain through a

legitimate neural inhibition and tell me

if this is still considered correct and

then I'll let you um uh elaborate on it

but I think that is an opportunity for

us to also talk more generally or for

you to educate us more generally on the

the mechanistic interventions for pain

like um maybe massage above or below the

sight of pain maybe acupuncture um so

again there will be chemical

consequences of any mechanical

intervention right as we know because

that's the language of the nervous

system electricity and chemicals but as

opposed to taking a drug you can imagine

using manual um stimulation or rubbing

around it or or perhaps we can also talk

about heat and cold so can we explore

that space a bit absolutely and first

you're right so uh in your first part uh

pack uh Patrick Wall Ron mzac luminaries

in the field of pain back in the 60s uh

defined the gate control theory of pain

and one of the things to build on the

story that we talked about with no

receptors going to the spinal signals

going to the spinal cord heading up to

the brain where the perception of pain

occurs that's not where the story ends

it turns out there are Pathways that

come down from the brain down from the

brain to the spinal cord that act in an

inhibitory role and we'll build on those

also from the

periphery we've got also fibers called

touch fibers these are the ones where

they get activated with light touch

stroking they refer to as a beta fibers

they're fast

conducting they head back to the spinal

cord and they make some

connections with those notive

fibers so with that grounding imagine

what you said your you hit your thumb

with a hammer you um uh you bang

something on an extremity uh what is the

first thing you do when you hit your

thumb with a hammer uh some people rub

it I yell some people swear and it turns

out there are studies that show that

swearing works really swearing reduces

pain better than uh than using

non-explicit

can go out and swear every time they're

in pain well they can but they'll have

to bear the consequences on an

individual basis we're not we're we're

absolving ourselves of any

responsibility right so uh rubbing uh

shaking is another one which basically

is activating those touch fibers oh it

is I do that everybody does that

everybody does that running it underwat

which you know it doesn't matter whether

you know in this case it's hot or it's

cold water it's the running of the water

underneath it and what ises it doing we

all think it's reducing the stimulus out

here and it is not at in the periphery

in the periphery what's magical about

that I think which is so cool is you're

actually changing the signals in your

spinal cord way back here in the neck

this is the cheapest free version of

what we refer to as

neuromodulation that's ever been

discovered um you're actually by doing

that you're changing things the

connections back in your spinal cord and

it's

reducing the no susceptive signals

coming in here that's why we do it and

it works it works beautifully that's why

when a kid gets their boo boo you know

parents come and rub it it works what

about the kiss the kids sometimes they

want to kiss you know or a romantic

partner will sometimes like injure

themselves I guess it depends on the

nature of the relationship and they'll

say like can you kiss it of course you

know then you kiss it and then like they

feel better is that purely

psychological well okay I think an

important point to to to ground here

when it comes to the experience of pain

is that everything when we say

psychological means Neuroscience I know

you know that no no forgive me I I I I

have to be careful with with the the

wording that I use that's my fault but

but it's it's accurate still it is

psychological but it is neuroscience

based I mean they're really becoming one

and the same but to answer your question

yes by kissing it you're activating

touch fibers we can also agree that

there's a positive emotional salience

that's associated with that and that

positive emotional salience is reducing

pain

too what interesting up wall and melac

sometime later uh there was the

introduction of a device to take

advantage of this called the tens device

and tens is an acronym transcutaneous

electrical neuros

stimulation and what the tenens device

is doing and there's many versions of it

now but there are those black electrod

you put over the area and they're hooked

up to wires and when you turn it on it

causes a buzzing

sensation and that buzzing sensation is

activating those touch fibers the a beta

fibers and so it's causing that

neuromodulation back in the spinal cord

amazing it's cool stuff it's very cool

and I and I love that you emphasize that

when we're rubbing the periphery or

shaking our hand the periphery again

being the body surface away from the

brain that the real mechanism of action

is taking place back in the spinal cord

because it really speaks to the the

body-wide and the the circuit wide the

nervous systemwide nature of this thing

that we call pain right it's it's

happening out quote unquote out here in

the periphery but it's being modulated

in the neck level of the spinal cord

approximately and then it's you know

being interpreted at the level of the

brain what

explains different pain thresholds I

could imagine it could be any or all of

the locations that we've been discussing

and it could be the context as well

right if you're um you know I've heard

before and I don't know if this is true

that if you have a lot of adrenaline

epinephrine in your system that your

threshold for pain goes way way

up there's probably a chemical basis for

that and maybe it's all you know um

anecdote but um certainly people have

different thresholds for pain I for

instance do not have a high pain

threshold but I've noticed I have a very

quick pain response so if I stub my toe

it feels like the most painful thing I

could possibly experience but then it's

gone very quickly so it's like a quick

inflection and then down other people I

know uh we've never done the experiment

I think I see them stub their toe and

they're like ah and then you know 10

minutes later they're still feeling the

ache so whose pain threshold is higher

it's a it depends on how you define pain

threshold so so how do we Define pain

threshold what determines pain threshold

and I guess the $6 million question are

there different pain thresholds between

men and women as it relates to the whole

story about childbirth being very

painful and that Women quote unquote

have higher pain thresholds I just I

just sent you about 10 questions forgive

me yeah um so what is pain threshold

yeah no it's a it's a great place to

start and

maybe I don't know if you want to Circle

back around at some point to the heat

and cold to finish up the mechanical but

for no no no you're let me answer your

get to your pain threshold so the pain

threshold is uh that stimulus intensity

that results in the onset of the

experience of pain the first onset of

the experience of pain so you know when

you turn up the heat it's it's not when

it's warm it's not when it's just hot

it's when the the heat

becomes the perception of pain like when

it becomes painfully hot at that point

in time the same works for cold you

mentioned some of the distinction

between your experiences of pain to a

stimulus and your buddies and that's

normal that first onset of pain again

those are those fast fibers those ad

Delta fibers boom right to your brain

those are the protective ones that when

we put our hand on a hot stove we

immediately Jerk it back we don't even

have a conscious perception yet that we

did that and then it's a moment later

when the sea fibers are getting up to

the brain and the other AD Delta fibers

are converging into conscious areas of

brain that we're like oh wow that stove

is really

hot and the ca fibers in particular are

converging on more emotional regions in

the brain that are conveying an

unpleasantness to that experience you

don't like it you and you don't want it

to happen again which is why it encodes

memories so you only had to do that once

as a

child now getting into the the pain

thresholds you asked one of the other

questions is do men and women have

different pain um thresholds uh the

answer the short answer is yes this has

been established

and I want to be careful here with

saying a couple things one is in general

uh men have uh higher paining thresholds

to things like heat stimulus than

women and what what people have to also

though

understand as scientists we make a big

deal out of small differences right you

know what we do is we take a group of

people in this case men and

women and we apply the same uh thermal

stimulus to them and we draw

averages the average man has this

stimulus the average woman has this

stimulus and we say well women have have

a little bit more sensitivity to that

heat stimulus and so we then go into the

press and we say uh men are tougher than

women that's a terrible statement right

because the tough part is a subjective

label right I mean it it it gets to a

whole bunch of different issues around

the Adaptive role of pain right I mean I

mean one could argue that if your

threshold for pain is lower that your it

serves a more adaptive function right

fewer injures Etc I mean I guess it gets

into the implications of what we mean by

quote unquote tougher it does but it

also misses I think the big point which

is people are not

averages so what I mean by that is um

while the average for a woman may be

somewhat less than a man if you look at

the distribution of the curves they

highly

overlap meaning the individual

variability within men and within women

is much greater than the difference

between men and women but there's plenty

of women on that curve that have much

greater heat uh thresholds than men Doh

but when you pull things you end up with

that difference unfortunately when

things are picked up and you want a

quick sound bite out of it that's what

it gets distilled down to so so it's not

unlike height for that matter I me there

a lot of women that are taller than men

that's exactly it but on average men are

taller than women on average and I would

say within this area of uh pain

threshold differences it's even closer

it's even

tighter you know it would be I'm making

this up the equivalent I think the

average height of a woman is 53 5'4 the

average height of a man 5'9 510 this is

Imagining the average height being you

know 5'6 for a woman and 5'8 for a man

you know it's not a huge

difference there's a lot of things that

play into to changes in pain

thresholds how much and this is where

the brain comes in because you know much

of the no subception much of the signals

that we're um transducing were

transmitting you know in many of us it's

very much the same it's when it gets to

the brain now it's shaped and it's

shaped by things such

as um your beliefs about that stimulus

your expectations around it how much

anxiety you're having at the moment does

increased anxiety increase one's

perceived pain yes okay yeah it does um

your early life experiences with this so

have you had traumatic experiences in

the past that alters brain circuits can

I interject a question yeah if one was

told just suck it up a lot or if one

whimpered or cursed when they uh hurt

themselves if they were told um you know

don't be a wuss don't be a

wimp do we know whether or not that

increases or decreases the subjective

feeling of pain later I could imagine it

going either way I could imagine the kid

that was told don't be a wuss when they

cried as a consequence of expressing

pain or an experience of pain secretly

feeling more pain because they aren't

able to express the emotionality around

the pain but that if we just look from

the outside we say wow like pretty tough

adult right because they're not um

crying out in pain so do we have any are

there any experiments that have explored

that I don't know you're getting into

this is a good point getting into um uh

pediatric pain and you know if there's

been experiments in that space I stay

mainly in the adult area and my

experience with raising a child is an N

of one with one son um he's done great

thank you I happen to know him very well

he's a he's he's what you call a great

example of Highly Successful

reproduction so you know it's say what

do they say it's better to be lucky than

good uh so sure I'm sure there was a lot

involved so don't don't discount don't

uh don't discard any credit thank you

thank you um you know my Approach with

Ian was not to say just you know

necessarily suck it up but I would uh

you know make light of it i' I'd have

fun with it and uh I would kind of laugh

and I'm like way to go buddy uh and I

would find he would often laugh you know

so I think a lot of it is the cues

they're taking off the parents you know

and again this is this is just my oneof

end parent is if they see you freaking

out kid's going to freak out too um but

does there get to be a point where

you're ignoring your child or your loved

On's painful issue yeah now you're

getting into some maladaptive some bad

space where I think it's sending that

person the wrong message and they may

very well have problems later

on I will tell just a very brief

anecdote when I was growing up I

observed a total of zero

children and friends who you know cried

out in pain or complained of pain who

were told you know um that was an

inappropriate response um sometimes I

might have heard parents say you know

come on just suck it up or like or rub

it you'll be okay that kind of thing but

once and only once with had some friends

I won't tell you what country they were

from but they they lived not far from um

where both Ian and I grew up since we

grew up near one another and I'll never

forget that the younger brother of a

friend of mine ran over to the father he

had cut his thumb on the band saw and it

wasn't particularly deep but he was

crying in pain and the father wrapped it

picked up his chin and smacked him

across the face and said don't ever do

that again and so what I think he was

doing was compounding the the lesson

about the saw yeah but clearly had no

regard for the pain that the that the

injury probably caused now I haven't

followed up with that kid um I think we

can all agree that by today's standards

that would be considered um abusive

parenting uh or perhaps um you know one

could say that was you know on the far

extreme of a response but I'll never

forget that and I went home and I I told

my mom yeah and she said oh yeah when I

was growing up that was actually a more

frequent response to kids hurting them

themselves especially boys and so things

have really changed in terms of how we

react to children in pain but the reason

I find this interesting is that

ultimately what we're talking about is

how should we interpret our own pain

yeah can I can I make a commentary about

that scenario and I want to bring in

another Neuroscience concept that that

Dad may have been doing

inadvertently and that's something

called conditioned pain

modulation so there's another cool

phenomenon in in pain that pain inhibits

pain so what I mean by that is when you

were you know this guy this kid but or

yourself growing up did you ever walk up

to your buddy and say you know my my arm

really hurts you know I injured it the

other day and what did what did your

buddy do they'd stomp on your foot and

you'd say why the heck did you do that

you I must have growing up with the same

friends oh yeah yeah and and they'd say

well now doesn't doesn't your arm feel

better and i' be like well yeah it does

and yeah I did grow up with those

friends I tell this story to some people

and I sometimes just get the wide eyes

like they did what yeah we are not

making recommendations here we're not

making recommendations but it's a real

phenomenon it was described by

Laars late 70s 78 or something like that

in rodent models initially and what

happens is that when you engage a no

susceptive stimulus or a painful

stimulus and a site distal different

from where the primary pain is it

engages a brain stem circuit that has

descending Pathways to the spinal cord

and inhibits pain amazing pain inhibits

pain it works it also is thought to have

some contributions from higher brain

centers we call this whole phenomenon

lears called this phenomenon diffuse

noxious inhibitory control or denck the

human version of this is called

conditioned pain modulation why I bring

this up not only to help explain that

father's actions

somehow I don't think that he was

thinking oh my kid's got a painful uh

you know hand or finger he cut himself

I'm going to slap him off the side of

the head he'll feel better I don't think

that's what was going through his head

he wanted to make him feel worse so he

didn't go near the band saw without

being more cautious but it probably did

reduce the pain a little bit to some

extent now where it's key is oh my maybe

we'll get into it later with chronic

pain is in some chronic painful

conditions the CPM or the denck doesn't

work m like fibromyalgia being

one um so pain inhibits pain uh is

another Neuroscience concept related to

pain that's rather

cool well and I'm sorry I missed your

question to could you repeat noing you

answer the question and and uh expand it

on it in a in a completely surprising

and far more interesting way than I ever

anticipated so thank you I I'm betting

that 98% of people listening to this

including myself have never heard that

pain inhibits pain incredible let's go

back to heat and cold we briefly touched

on heat but let's talk about the use of

uh quote unquote therapeutic heat or

therapeutic cold a cold pack for a you

know a you know a bruise that really

aches or maybe even a break or a sprain

or heat you know the in the world of

sport physio cold is now heavily debated

localized cold is heavily debated you

know you get people saying things I

don't know if this is true that you know

it creates a sludging of the of the

fluids trying to head in and out of the

injury so cold is not as good as heat

heat allows for um the uh inclusion and

removal of waste products and you know

there are all sorts of Just So Stories

that people make up some of which might

be true I don't know but what do we know

about heat and cold as physiological

stimula in terms of their ability to

ameliorate to help pain because of

course if you get things hot enough or

you get them cold enough you can create

pain with heat or cold but let's assume

we're not getting to that level of heat

or cold and one is in pain um you know

when I was a kid we had a hot water

bottle that for times when we were sick

with something but sometimes you know if

I felt an ache on the side I'd put some

hot water in the hot water bottle lie on

that thing watch some cartoons i'

definitely felt better sure sure well

putting aside the Contemporary

controversies over the mechanisms you

described which are I think very real

and need to be sorted out traditionally

historically we tend to think of

applying cold for the first 48 hours or

so after an acute injury and then heat

thereafter cold has some really cool

effects cold uh reduces inflammation so

it reduces some of the release of those

inflammatory chemicals we talked about

prostaglandins cyto histamines um other

chemo kindes all these fancy terms for

substances that

sensitize the primary

Noor and it reduces the release of those

and it reduces inflammation another cool

thing often not appreciated is nerves

don't fire as fast when they're cold and

so if you've got no acceptors that are

firing and you put

cold it's slowing the number of signals

coming up and by definition it's

reducing the the the ultimately the pain

you're experiencing now heat heat has an

obvious effect of increasing blood flow

it's going to help uh relax muscles and

get blood into those muscles and that's

probably why you were putting that hot

water bottle on um and it just darn

feels good and so what what do I tell

people you know in part I tell people

use whichever works best for them um I

find there's huge individual

variability in whether people like heat

or like

cold and within

reason uh they're safe what do I mean

within reason don't go putting an ice

pack on an extremity for two hours you

know you'll get a

frostbite so you know take care with

that how cold should one make the point

on their body that's in pain assuming of

course that they're not going to give

themselves frostbite meaning do you want

to numb the area you know get past that

point point where it's a little bit

painful and then that you know basically

you're shutting down some neural

Pathways and you don't feel anything

there it's numb and then you let the

blood flow return When you remove the

cold pack is that I mean that's a

reasonable suggestion okay yeah all

right well people I think will

appreciate that the um the specifics of

that because um you know and of course

listeners of this podcast often are

interested in whole body deliberate cold

immersion you know cold showers ice

baths Etc most people experience those

as somewhat painful as they get into

them yeah and then can experience some

numbness when they get out is it

possible to raise one's pain threshold

through the regular exposure to pain in

ways that are safe such as deliberate

cold exposure assuming that one doesn't

stay in too long and it's not too cold

um and or through you know we were

talking about sports earlier but just in

general like can we raise our pain

threshold so that life is less painful

the short answer to your last question

is yes um the answer to your other

question about about uh extreme cold and

cold exposure which I know you have a

lot of expertise and you can teach me a

lot I'm going to stay in my wheelhouse

at because I I'm not up on the

literature in that space even in its

intersection with

pain um it's an intriguing concept uh I

have to

imagine that it makes sense you would

get some

habituation uh with that repeated

exposure I think one of the the

questions that would come up with for

instance the cold exposure Ure and I

don't know the answer to this but it's

I'm sure maybe somebody out there does

is is there cross

modality um changes in pain thresholds I

mean if you expose yourself a lot to

cold does it change your heat thresholds

I don't I would surprise be surprised if

it did yeah would or your pressure

because those are separate parallel

Pathways yeah yeah you know there uh and

you know as an aside I hate the cold but

I do really well with the heat you know

and so does Ian uh you know I think

there's something genetic there uh so

you know I mentioned earlier around men

and women and heat uh thresholds and I

chose that specifically but each of

these are different depending on the

stimulus

modality can you change ultimately your

thresholds yeah where that involves is a

lot of cognitive control it's a lot of

cognitive training uh around that

space

and you know there's there's clearly

approaches to that

people have learned that there's

different manipulations around that

so one experiment this wasn't intended

at least I don't believe so they were

measuring uh heat thresholds uh on

college students and and we we

experiment a lot on students as as we

all know we pay them well um and what

they found is that when they're studying

guys studying dudes when there was an

attractive woman who was delivering the

stimulus the thresholds were

higher because the guys did not want to

look like a wuss in front of this

attractive young woman and that's been

pretty well established so the

experimenter their

gender uh plays a big role in that has

the reverse experiment also been done I

don't I don't know I don't know

interesting um but getting back to your

point Point yes um I think through a

number of uh you know cognitive

manipulations you can ultimately um over

time change those thresholds another one

area is ex is movement

exercise you know clearly changes uh

those thresholds over time you are

probably building up um some increased

inhibitory tone through that process I'd

like to take a quick break and and thank

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docomo one thing I'm fascinated by in

the whole mindfulness space yeah uh is

this idea of whether or not under

conditions of stress or in this case

pain whether or not the most adaptive

mindset assuming it's not a tissue

damaging level of pain would be to think

about something else distract oneself

from the pain or conversely whether or

not one should quote unquote go into the

pain so for people who have chronic pain

Maybe it's in a a small area of the body

that experiences chronic pain pain quite

often AK chronic pain or maybe it's

whole body pain I don't think it really

matters for the question I'm asking and

people are trying to develop some

cognitive ways so what we call as

neuroscientists you and I top down

mechanisms for like okay I'm going to

distract myself from the pain I'm going

to focus on other things I really enjoy

or rather I'm going to really go into

the pain meet the pain and realize I

don't know somehow that it's not as bad

like somehow there's a and again this

becomes very opaque right we don't

really know what we're talking about

when we when we do these sorts of

protocols but those sorts of things are

out there in the mindfulness space and I

think um I certainly take mindfulness

seriously as as an intervention but what

always bothers me about those sorts of

interventions is that they lack the

specificity and the granularity and

there's no kind of mechanistic logic to

explain them so what what are your

thoughts on on meeting the pain versus

distracting oneself from the pain let's

break that down because there's two

concepts there as you alluded to and

they're both effective and they both

work

differently so one is attentional

distraction where you are distracting

yourself from the thing that is causing

pain clearly works in a lot of

people and that's why one of the

strategies that we recommend for

patients for people living with pain is

to engage in distracting activities read

a book um uh go for a walk um spend time

with friends and family in particular in

the community and work to get your mind

off of pain what we've learned is it

that attentional distraction engages

specific brain networks they tend to be

some of the outer layer of brain

networks in your prefrontal cortex some

in your singulate cortex

um in other regions which are clearly

involved with distraction it's not

necessarily that distraction is going to

completely eliminate one's pain but it

can reduce it uh significantly and this

is

why the

biggest problem with distraction from a

time of the day is at

night it's when people are trying to

sleep during the daytime you can read

that book you can spend time with

friends and family but people with

chronic pain that have it 24

seven you can't distract yourself at

night when you're trying to get into a

relaxed State and fall asleep and that's

why sleep is such a big issue for people

with chronic pain so attentional

distraction it it works distraction

works now what you said I mean the

second piece you said kind of let's meet

the pain if you will and there's

different approaches to meeting the

pain one approach that you invoked with

mindfulness is

is addressing the pain from a

non-judgmental accepting

manner I'm aware the pain is there I am

not going to judge it I'm not going to

put a value on it's bad it's good or

anything I'm just going to note its

presence and that has been shown to work

as well in fact actually when John kabat

Zen originally developed

mindfulness-based stress reduction

people with low back

pain PL Studies have shown that it works

I've completed just some recent studies

in

mbsr uh as well and we're diving deeply

into the data so it's this

non-judgmental acceptance if you will of

the pain sorry mbsr is the acronym for

mindfulness based stress reduction

mbsr everybody should do mbsr let me be

C I have no Financial relationship with

any of this by the way but

mindfulness-based stress reduction has

been shown effective for anxiety for

depression for pain just about

everything I think they should put it

into all the

schools uh it's it's a great skill to

learn no side effects takes a little bit

of time to learn

it and uh it can be in some people

effective and helpful for pain and

that's the key that we're going to keep

coming back to is some of these things

work for some of the people some of the

time there's a third aspect of meeting

the

pain and that is more of a

direct cognitive reframing about the

meaning of the pain

now you're coming at the pain and you

have um an approach you're making effort

on what you're thinking of the

pain is that pain damaging threatening

harmful or do you view it as yeah it

hurts but it's not harming

me that is a critical

critical aspect of pain management and

that is serves as a foundation for

something called cognitive behavioral

therapy the the cool thing about a

number of these is that there's actually

different neural circuits

engaged with these different

approaches and um I think the key that

we have to figure out and this is where

research is going is which approach

works for which person under which

circumstance so interesting uh something

you said about understanding the pain

but not um overinterpreting or

catastrophizing the pain seems important

knowing the difference between being

hurt or feeling hurt versus being

injured has been something that's been

important to me I've been involved in

sports uh where clearly pain was

involved it's like I'm hurt but am I

injured that's the first question you

know like I've rolled an ankle like oh

you know like I'm limping this hurts am

I injured meaning am I going to be back

at it in an hour tomorrow versus I've

broken bones and it's you know you know

great empathy for anybody that does like

when you're injured you feel the snap

and you know you're out for a while in

some cases um so I think knowing the

difference between being hurt and being

injured is something that's kind of that

key moment and for me it's always been

experienced as a moment of anxiety after

feeling pain especially in a sports year

like uh oh like am I am I going to have

to take two weeks off or is this just

pain so I think for people to be able to

recognize when pain is reporting an

injury versus when pain is just

reporting a temporary sensation is

really important and perhaps also for

psychological hurt versus psychological

injury I mean that gets to some larger

context themes these days of somebody

says something it upsets us are we hurt

or are we injured right you know I think

it gets very

murky how does one determine if they are

hurt versus injured and then maybe we

could even stretch into the

psychological realm neither of us are

psychologists but it sounds like so much

of what you do represents the the bridge

from the body into the mind and so you'd

be remiss if we didn't talk about

emotional pain as well yeah so what you

just said your spot your spot on Andrew

and that one of the key messages the key

you know macky's tips for pain

management is to understand the

distinction between hurt versus

harm versus harm MH

critical absolutely critical let me

allow me to illustrate with

um patient I saw won't name names some

time ago guys's in his 40 is a master's

level tennis player tennis is his life

he's works as some executive somewhere

but he lives for tennis comes hobbling

in on

crutches sits down and he's got pain in

his foot and he was told not to put

pressure on his foot because he's got

this injury and it's going to be worse

and this has been going on now for

months and he's now depressed because he

can't play tennis tennis is his life

this guy's life is tennis so I examine

this guy and it turns out what he has is

something called a Morton's neuroma and

a Morton's neuroma is a fibrous

thickening of tissue around the nerves

that go to your toes and it gets to be

like this bundled tissue nerves and it's

really

painful um it's very

painful but it's not causing

harm there's no harm there it's really

painful so I explain this to the guy and

he looks at me with like this light bulb

goes off and he's like you mean I can

play

tennis and I'm like yeah guy you can go

play all the you want it's just going to

hurt he got up he left the crutches in

the exam office and he walked

away now that's an extreme example I

don't want people please to think that

that kind of thing occurs all the time

it doesn't um chronic pain conditions

are often incredibly complicated and

need much more than you know a 45 minute

or 60-minute education session and you

know back to the tennis court he still

had pain in his foot by the

way but he could play but that gives

that example of

addressing that fear and the anxiety

around that that issue and I think

that's what we first have to learn is

does that pain that we're experiencing

represent something that is harming us

that something that we either need to

seek a medical attention now or sometime

soon and whether does continued

activity worsen the tissue injury or not

in my world where I'm caring mostly for

people with chronic

pain we've moved beyond the tissue

healing by definition by one of the

definitions for chronic pain is that the

pain

persists beyond the time of tissue

healing so in many of our sessions our

times we're educating people hurt versus

harm it's back pain we we evaluate the

spine we make sure is the spine stable

is there anything Sinister causing

damage in most of the cases it's not and

we help people understand that

distinction critical critical for

people and yet at the same time you

don't want to just ignore

something that is a real medical issue

that's getting worse and needs medical

attention and that's where the

complexity of all this comes in did I

answer your question yeah beautifully I

think this distinction between hurt

versus harmed is so important for people

to hear um perhaps you're willing to

expand a little bit in terms of the

psychological hurt versus harmed I mean

I'm not asking you to comment on um

societal or generational shifts but you

know we'd be avoiding the obvious if we

didn't say that in the last um really 10

to 15 years there's been a pretty

dramatic shift in terms of how Society

at large interprets emotional pain right

people hearing things or seeing things

and the idea that emotional pain could

be related to physical pain or at least

similar enough to it that people's

emotional pain is valid right and if

anything I'm here to validate the fact

that emotional pain is valid like any

other pain except it is different

because it becomes very hard to point

to a specific kind of threshold we're

using that word a lot today but I think

it's appropriate here threshold between

hurt and harmed whereas if I tell you

that my left foot hurts which it did a

lot in high school and then you took an

x-ray of my foot in high school you'd

say your foot's broken because it was

broken a lot in high school and that's

harmed I mean to continue to do what I

was doing to break it in the first place

I was harm clearly going to harm myself

worse so I had to had to heal up but

when it comes to psycholog iCal pain you

know Psychiatry has all these thresholds

for normal functioning versus abnormal

functioning are you sleeping well normal

relationship and on and on we don't want

to go there because that's not our place

but how do you when you see patients how

do you take into account the level or

the thresholds for their emotional pain

because that's part of your job so I'm

asking you this from the perspective of

a somebody who treats pain how do you

gauge somebody's psychological pain is

it by how intensely they vocal ize their

pain or does it always go back to how

well or poorly their life is being

managed at the level of sleep nutrition

relationships and so forth yeah great

great set of questions there's a lot in

there let me first start off with

something very

simple I don't try to distinguish

between this notion of psychological

pain physical pain it's pain and of and

of I think once I get into where you get

into this trying to distinguish is this

psychological pain or psychogenic pain

which was a terrible term or physical

pain you end up putting value judgments

on people and I don't think it serves us

well when we're caring for the person in

front of us if they're in pain I'm

addressing the pain the thing to note is

at least in people that come into our at

Stanford Pain Management Center and

other pain centers is that remember pain

is a sensory and emotional experience

it's all wrapped up and so we want to

treat the whole

person sometimes we get we get easy we

get easy ones and we just go do a nerve

block and pain goes away and that's

simple but usually it's much more

complex where we're seeing the

interaction

of uh an expression of pain that

includes includes a significant amount

of anxiety of depression you mentioned

this term catastrophizing which we can

break down if you'd like and that's

probably one of the biggest

predictors factors in uh in

amplification of pain and worsening pain

and poor treatment response is

catastrophizing um I try to treat the

whole person and not really partial out

all this I do at Stanford I you I built

a digital Health System that captures

measures a lot of data around a

patient's experience across physical

psychological and social functioning and

we use that

data to Target therapies to understand

um how much their depressive symptoms

are anxiety anger anger big issue in

pain huge in pain does it make it worse

or better invariably it makes it worse

yeah and you know you can break anger

down in a couple different categories

John Burns and others has broken it into

like anger in versus anger out I don't

know if that term is familiar with

you um anger out that's my

father um loud loud angry

boisterous banging you know would

quickly turn anything into an angry

tiate anger out expressive yelling at

the at the news yes yelling at somebody

who cuts you off in traffic usually

yelling at the man uh cuz he hated job

um anger

in boiling simmering you know

self-contained

seething that's anger

in data seems to support anger in is is

worse it's bad so it's not necessarily

whether or not it's directed at someone

external in both cases anger in and

anger out can be directed at someone

external it's a question of whether or

not it's expressed outwardly or

contained inside beautifully stated

beautifully stated so we C you know

anger depression anxiety uh we capture

fatigue sleep and so what we try to do

is again look at the whole person

because they're not just a back if

that's where they're having pain or not

just a neck or a shoulder in your case

it's impacting the whole person and we

just got done talking earlier about how

all of these circuits interact with each

other and so sometimes we can't just

eliminate the no susception in the

periphery sometimes we can reduce it but

what we have to do is Target everything

and we have to try to Target all these

circuits up here and in many cases what

we're doing is through education through

pain

psychology um through physical therapy

and re rehabilitative approaches on top

of it and yes the medications we have

now you know we touched Bas on a few

earlier but we have over 200 medications

available for pain um very few of them

FDA approved

uh we tend to steal from all the other

fields so you're talking about more than

200 medications that can be yes

prescribed for pain but as off Lael

treatments perfectly stated yeah there's

only a few medications that are actually

FDA approved specifically for pain so

what we what we do is we borrow or steal

from the psychiatrists some of their uh

their

anti-depressants uh which will

frequently work very effectively for

pain and work on those pain related

circuits in the

brain we uh take from the neurologist

some of the anti-seizure medications

because those

medications um while reducing separately

seizures for people who don't have

seizures they work on ION channels um

they work on other neuromodulators that

also are involved in pain circuitry we

can take from the cardiologist

medications that work on the heart anti-

arhythmia or heart rhythm drugs they are

potent sodium channel blockers and the

sodium channels as you know are

responsible for the action potential

that generates the nerve impulse signal

and so they're like an oral local

anesthetic that you take and so we we we

take from everybody in our field in the

medications getting back to to what you

said

so just summarizing one I I don't really

distinguish

uh psychological versus physical pain in

my world I I find it better just to

treat it as pain and look at the person

holistically and go after all the

components at once I find that's where

we get the best

results and it is typically bringing a

lot of tools to Bear speaking of tools

to Bear What role if any does nutrition

play in local or whole body pain I

critical and I think we're learning more

and more and more

about uh the role of good nutrition of

healthy eating anti-inflammatory diets

uh avoidance of foods that are

triggers

um and an incredibly underappreciated

area

um you know I've had my experiences with

chronic pain um

I developed uh an abdominal chronic pain

problem uh shortly after I turned 50 I

was throwing a happy hour for our pain

psychologists of all people went to a

Mexican restaurant I won't name which

one got food poisoning That's why I'm

not naming it good Mexican food bad food

poisoning and ever since that event I

can't eat anything in the onion family

what um I'm familiar with with onions

but what else is in the onion family I'm

sure you've researched this now pretty

thoroughly considering what you're

describing classic and the what we refer

to as fod Maps you know it's one of the

fod maps and I have now some issues with

the others and um manifested by just

severe severe up abdominal pain and um

not many other symptoms but you know it

put me on this journey where uh severe

abdominal pain didn't know why couldn't

sleep

couldn't sleep went like I'd go months

without having a restful night's sleep I

thought I was getting early Alzheimer's

because I felt like I was getting

stupid and um what actually benefited me

was of all things the pandemic why

because what did we all do we isolated

we started eating the same foods and I

started noticing I was feeling better

when I was eating certain foods my

abdominal pain went away and I'd start

doing as a scientist

experiments and I finally was was able

to isolate and determine what the

problem

was so now I have complete avoidance on

that I'm I'm a little difficult to go

out to a restaurant and have dinner but

you know so no onions no onions and what

else shallots chives scallions leaks

anything in the onion family you know

not alium I'm fine with

garlic

and you know by healthy eating by

identifying something by triggers

changed my life

and return to a degree of normaly I

think the key for people is you know if

you have any kind of similar issues

identify those

triggers sometimes uh isolation of you

know Foods or restrictions and using a

journal and then as you learn from that

slowly build Foods back into your diet I

think it's so important for people to

hear this and thanks for sharing your

personal story around this because I

think that nutrition while every

physician seems to appreciate that the

quality of nutrition matters defining

what quality nutrition is is really

difficult there's still you know Avid

even we could call them ranous debates

about this you know vegan versus

omnivore versus this and you know but it

sounds like this is a case where it can

become very individualized but I could

imagine somebody going to their

physician and that physician not being

you and saying yeah you know I notice

that when I eat certain foods I'm in a

lot of pain and the physician simply

saying well don't eat those foods but

unless that person is a trained

scientist like not knowing how to go

about doing the sorts of experiments

that you did would be difficult

impossible I'm sorry I know I interrupt

you I just want to build on that if I if

I can one of the key things I simplified

my story but the key thing is is if I if

I eat onions or anything that onion

family it's pain for two weeks wow it is

so the thing is

is if you get repeated Expos exposures

it never stops and it gets very very

hard to figure out what it was so it's

not like you eat something you get pain

it goes away where you know we can all

do that pattern recognition here you

have to be able to think back what

happened two weeks ago that may have

influenced it so it's not easy well this

may be a case for elimination diets

which are uh provide they're done safely

where people restrict the number of

foods they eat to a very limited number

of foods make sure they still get enough

calories and macronutrients uh that they

need protein fats and carbohydrates or

what what have you but that by limiting

the total number of foods that they eat

to like eight or 10 basic things then

you can build things in and then explore

what triggers the pain or what removes

the pain I don't really see any other

way I am intrigued by The Onion example

even though it's a it's a it's your case

in particular and we don't want to

extrapolate too broadly is there

something about onions that's triggering

a particular neurochemical or immune

pathway

do we have any knowledge of like why

onions would create that kind of gut

pain this has been a journey I've been

on now for a few years to answer this um

uh one of our GI pain docks that we have

come in the Clin lyen newwin sent me a

paper from I know Sellar nature that

showed that after a gut

infection it can change the genetic

expression related to sensitizing you to

food antigens I know I throw out a lot

of jargon there basically the short

answer is you get an infection and your

gut no longer

responds properly to a normal food

item and so one explanation may be I got

this infection I was at a Mexican

restaurant a lot of onions and I got

sensitized through that infection now

subsequently to onions you know I saw a

Stanford uh allergist Hannah Watford

who's awesome by the way and uh after I

had this I think figured out and I went

in and I'm like well you know Dr Watford

is there anything I can do for this and

she laughed and she's like no you're

doing everything it's all just

avoidance and I thinking I was rather

unique and special about this thing I

said you know do you ever see this and

she said oh yeah I see this all the time

every day I see this all the time and I

said like this isn't unusual he's like

no I see this thing all the time and

this thing meaning sensitivity stivity

to certain know to certain to different

these different food groups and this

this thing that occurs later in life

something an event that happens to

somebody that

triggers and I said well gosh that

sounds like a public health problem and

she's like that's what we're debating

right now in the allergy Community is

whether this is representing more of a

public health issue and is because I'm

seeing I Dr Watford I'm seeing

increasing amounts of this uh as we go

forward how interesting well um this is

not a time to plug the philanthropic arm

of our premium podcast but uh I'm very

involved in science philanthropy this

sounds like an area to De devote some

funding to to explore how foods are

impacting the local and systemic pain

response yeah I I got in you know so I'm

running a large biomarker study to

characterize people deeply and one of

the things that I wanted to put in there

is microbiome characterization now to be

clear that's out of my wheelhouse but

the beauty of being at Stanford and

other major institutions is you can go

make friends yeah Justin sonenberg who's

been a guest on this podcast is one of

the world experts on the gut microbiome

we have a few others too so there you go

so he's a friendly guy I'm sure he'll

collaborate we go we go make friends and

people who understand the microbiome we

collect the samples and that's where

team science is magical and once again

the idea looking at the whole

person as long as we're talking about

the gut um let's talk about pain inside

the body because we talked about NOS

acceptors on the surface of the body and

the pain that most people uh immediately

think of when you have a discussion

about pain is you know pain on the

surface or a broken bone or maybe hip

pain or knee pain or back pain but what

about pain that resides deeper in the

visera you know uh gut pain um irritable

bowel syndrome these things are I'm

learning are far more uh common than um

that I knew I'm fortunate that um if I

have a stomach ache or a headache it

means something's wrong I rarely get

those I've sometimes been called you

know have a stomach of Steel not because

it's hard from the outside um but

because I can eat pretty much anything

although I eat pretty cleanly a lot of

people write to me and ask questions on

social media about irritable bowel

syndrome and other forms of gut pain and

viscera pain like pain that they feel is

really deep within their system

typically how is that sort of pain dealt

with at a clinical level absolutely

visceral pain is a different thing than

what we been describing uh a lot of

which is sematic Pain by the way I'll

say as an aside I used to have a gut of

Steel also I could Chomp down anything

anytime anywhere and so you know there

was a lot of grief and loss associated

with not being able to eat certain foods

and uh that's also something people have

to come to grips with um but getting

back to visceral pain so the thing about

setic pain that's another term now itic

meaning the Soma the the the extremity

that you are alluding to is the no

acceptors there uh very precisely

localize where the stimulus the painful

stimulus is coming from when you hit

your thumb with a hammer you know

exactly where that pain occurred with

the visceral pain what you have are very

diffuse what we refer to as receptive

fields think about you last time you had

a stomach ache it's not that you put

your thumb right here you said is kind

of hurts like this your whole stomach

whole stomach it's because those

receptive fields are very large they're

broad they're not as well localized and

in part the reason for that type of

broad receptive field is you're not

trying to get away from localized

danger so when people get stomach AES

it's often a very Broad Brad area when

you get pelvic pain it's the same type

of thing

now there's some fascinating stuff that

occurs with visceral pain because those

fibers that extend from the viscera

meaning the the lungs the abdomen the

pelvis they all head into the spinal

cord

too and it just so happens that they

make kind of indirect direct connections

with the same

level that represents the

body

so let's think about pelvic pain for

instance you frequently will find people

that said that have pelvic pain that

will describe having lower back pain

too and it's because of this visceral

somatic convergence in the spinal cord

it's not that there's something going on

in their back it's that these signals

that are being driven heavily from the

pelvis are coming in and connecting with

the same regions from the

back and the convergence of that is now

being perceived as pain in

both and we we were seeing that more and

more in the research this viscerosomatic

convergence people have pain in their

pelvis and then also over their abdomen

um classic one that uh we're aware of we

see this in the TV the movies and

unfortunately real life are heart attack

so the visceral fibers that subserve the

heart typically the first through the

fourth thoracic region well those

converge um in the spinal cord in

similar regions that subserve sensation

under the arm and up here that's why

people will often say they've got pain

with a heart attack radiating down into

their arm the left arm typically the

left arm the heart is on the left side

exactly

um after people get abdominal

surgery Sometimes some blood can leak

out and it'll slip underneath the

diaphragm the diaphragm is subserved by

some of those neck regions three four

and five of the cervical which happens

to also cover your shoulder and so

you'll get people after abdominal

surgery they said man my shoulder's

really hurting me

Doc and what we do is we first check to

see you know could something have

happened during an you know during

placement just make sure there's nothing

wrong but frequently it's due to

irritation that's again one of the

magical Mysteries it's so fascinating

about

pain it seems like a good point to bring

up referenced pain um or is what you're

describing an example of referenced pain

so my understanding of referenced pain

is that you know like for instance I

I've got a slight bulge at I think like

my lumbar 34 disc or something I had a

whole body scan recently just a um an

exploration scan cuz I had the

opportunity not not anything serious

fortunately and there's a slightly bulg

disc there and every once in a while if

I do certain movements um in the gym

I'll get pain down in my right hip and

sometimes going down my leg and I used

to think it was sciatica cuz you assume

anything on the right back side okay

must be wallet induced s sciatica back

pocket wallet into sciatica um but what

I eventually realized is that well it's

this dis buul it just so happens that

the nerves that emit from that that

region um they Branch out to a bunch of

different areas and so you think the

pain is in your leg but the the issue is

someplace else or um and occasionally

indeed I feel the pain elsewhere in my

body as well it's sort of like a like a

matching of regions for pain that seem

unrelated is that a way to think about

reference pain perfectly the the the

examples also I referred to of a heart

attack causing referred pain or also the

pelvic region associated with back pain

as a way of um referred pain um what

you're describing is the fact that pain

doesn't have to start with an injury or

a stimulus in the periphery you could

damage the nerves anywhere along the way

and that will be perceived as pain we

refer to that as neuropathic pain so

that's another distinction you brought

up uh nicely good good segue into

there's thought to be um several

different types or categories of pain we

have been talking through much of this

time about somatic pain you know injury

out here we talked about visceral pain

and when you have damage to a peripheral

nerve damage injury to a peripheral

nerve or the central nervous system we

refer to that as neuropathic pain

it frequently has different qualities

different characteristics people will

refer to it as shooting stabbing shock

like

burning it can frequently uh when

there's a damage to a nerve or damage to

certain regions of the brain be

incredibly challenging to

treat by the way the good news is with

that uh light disc bulge is the vast

majority of time the discs reabsorb yeah

I have to be careful to not do too much

um

spinal flexion like sit-ups and stuff I

thought that that would help but that

actually doesn't strengthen the back it

was actually a asymmetry between the

abdominal muscles and the lower back

muscles so provided I do a lot of back

extension type training then that bulge

more or less stays in I just have to be

a little little cautious not too

cautious fortunately as long as we're

talking about referenced pain somatic

visceral and all the rest what about

associative or referenced pain where

it's psychological and I don't want to

get too abstract here but more and more

these days I hear from people who say

you know I was in this job and the job

sucked or I was in this relationship and

the relationship sucked and I had

terrible back pain like really acute

localized back pain or chronic headaches

or migraines yeah and then they go on

vacation or they change their

circumstances and lo and behold the pain

goes away does that surprise you as an

expert in pain not at all not at all

what you're you know simp simplistically

referring to is you know there's people

are undergoing

stress and we

have we clearly know that the brain is

not a passive recipient of information

coming in from the body it's a two-way

street the brain is causing Downstream

consequences in the body the brain uh

controls our sympathetic nervous system

and parasympathetic nervous system the

sympathetic being the fight andlight

response it controls the tone of uh

cortisol that's being released and we

all know that in acute

situations rapid increases of cortisol

and um nor adrenaline is keeps us away

from the Lions and the Tigers and the

bears oh my but in a chronic situation

and uh Robert spolski as you know at

Stanford has built a career around

chronic stress at least in part and very

bad for us and so these chronic

stressors impact the end organ the

tissue and it's real pain it doesn't

mean that we need to go get back

surgery it means that probably we need

to identify the stressors that are

contributing to that and address those

and we'll often find that in the

scenarios you outline that the pain gets

better um some of those targets are

interesting um there's a lot of memory

associated with pain this is where early

life events

occur and those early life events and

injuries can sensitize us to Future

vulnerability so I was in a car act bad

car accident when I was

16 uh fortunate to walk away from it got

bad whiplash

if I get stressed a lot of my pain

manifests in my

neck for me as a pain do it's a signal

to me that's

like go work out go for a walk in the

forest you know uh and take some time

away from the

computer again that's a simplistic

message and my experience doesn't

translate into everybody else but I'm

just validating every everything that

you you

said let's consider the opposite

scenario which is positive emotions uh

you've done some very nice studies

exploring how being in positive

relationships being in love in fact can

change our perception that is our

experience of pain and probably does so

at real physiological levels as you

mentioned earlier psychological is

physiological and vice versa it's hard

to separate the two but could you share

with us uh what you did in that study

and what you found because I find it

really interesting and it also points to

the incredible power of love in uh how

we

experience life yeah yeah I think

there's several cool things about that

study that I love to share one is how it

all came about so um you know us

Neuroscience Geeks often go to the

society for Neuroscience as an annual

meeting and I was hanging out and uh

sharing a room with art Aaron who

studies passionate love and he and his

wife study passionate love and we were

having a glass or two of wine and I'm

asking art have you ever you know have

you ever studied pain he's like no I

study love and he's like have you ever

studied love no I study pain if has

anybody ever studied the intersection

another glass of wine no let's do it so

we came back to Stanford and there was a

young postto Jared younger who's now a

professor at the University of Alabama

and I said Jared we were either going to

fall flat in her face or we're going to

this is going to be a cool study and

Jared took this on great job so what we

did is we advertised on campus for

couples in an early phase of a romantic

relationship

because there's a reason for choosing

that in an early phase of a romantic

relationship you are deeply focused on

your beloved they're on your mind all

the time you feel great when you're with

them you feel terrible when you're not

with them doesn't that just sound like

an

addiction I mean it's that yearning uh I

don't know that's it's a can be a

pleasant experience but addictions you

know for the people who are using the

substance can find it you know in that

early phase very pleasant but it it

turns out that the early phase of a

romantic relationship engages the same

neural circuitries as addiction

interesting same reward circuitry all

that so we chose that and so he said

come to us and bring pictures of your

beloved and bring pictures of an equally

attractive acquaintance clothed this

isn't sex that we're studying uh

clothed and we caused them pain in the

scanner and and and we paid them

afterwards um we

needed a control condition for this

because thinking about your

beloved is very uh attentionally

demanding remember we talked about

attentional distraction earlier so we

gave people what's called a word

generation

task very simply um can you think about

every sport that doesn't involve a

ball okay uh frisbee hockey boxing

boxing okay that's attentionally

demanding think about every vegetable

that's not green and you know so you're

running that through your head and we're

causing you pain it's an intentional

distraction task

so we flash people pictures of their

beloved cause pain flash people of their

acquaintance cause pain and then

distraction okay what did we find love

works great love works great it was a

wonderful analgesic it significantly

reduced people's

pain and it turned out the more in love

you were the more pain relief you got

when viewing the photo of the person you

love yes when View doing the photo of

the person you love now how did we know

how much in love they were it turns out

the psychologists have got scales for

everything and one of them is a

passionate love scale which asks how

what percentage of the day are you

preoccupied thinking about your beloved

oh goodness you just sent people now off

to give their Partners the passionate

love scale to figure out how much time

they're spending thinking about them

yeah we we had Stanford students some of

them thinking about their beloved 80% of

the day uh I wanted to use this as a

screening tool for our resident

applicants because uh I I I want them

focusing on patients not their beloved

and that is by the way a joke that bad

joke but but probably is real world

we're not just talking about Stanford I

mean but when somebody's writing you a

script or a prescription that is or

giving you advice um yeah you might want

to know if they are in a new romantic

relationship yeah so the the the other I

thought the other uh cool thing about

this study was attention worked also but

attention

and love worked on different

circuits so attentional distraction they

worked equally well attention again

worked on some of these prefrontal

regions these outer cortical

areas love worked on more of what we

classically think of is these

reward-based circuits the nucleus

accumbens uh the amydala

um one of the the descending uh brain

stem regions called the substantia

which is coming down from the brain

through that area to the spinal cord to

inhibit pain so classic addiction

Pathways classic and so the key again

message for people is um different what

we would think of as psychological

approaches engaging different brain

circuits to reduce

pain I'll leave you with one last uh

side note that we didn't publish on and

that is uh Jared went back a year later

and we assessed the student strength of

their relationship if assuming it was

still ongoing and he found that there

was a rather High correlation between

the love induced analgesia and brain

activity and the cadate nucleus and in

the insular with the strength of their

relationship a year later it was so we

had a brain scan that was a predictor a

future um strength of a relationship

could you tell us the direction of those

results so if a new romantic partnership

is uh creating high levels of activity

in these two brain areas you just

mentioned then it is a very good

predictor that the relationship will yes

survive over time well in this limited

sample it meant that it it was going to

be very strong a year later um

understand and you know Andrew we always

have to put these caveats unpublished

non-peer reviewed it was a fun post Haw

data analysis that I'm not sure if

anybody's ever you know run with those

kind of things no but we can explore it

in a in a playful way now and people can

do with it what they will it does sort

of speak to something important though

um assuming that result would hold up if

the same experiment were done and you

know many hundreds or thousands of

people it sort of speaks to the idea

that the activation of these addiction

likee circuits in the early phase of a

passionate love

relationship set in motion

a certain number of things that create

stability in that relationship which on

the face of it um makes sense but we've

also all heard of the opposite way of

well as well which is you know um Fools

Rush In or that uh things that start

fast end fast or things like that but

here you're talking about um the early

phase of passion serving this

interesting role in terms of analgesia

uh alleviating pain but also predicting

some stability of the relationship over

time it's kind of interesting it's

fascinating to talk about uh you know I

feel like I have to put that caveat in

that not generalized but a fun thing to

talk about and it's where I think cool