How to Control Your Sense of Pain & Pleasure

- [Andrew Huberman] Welcome to the Huberman Lab Podcast,

where we discuss science and science-based tools

for everyday life.

[bright upbeat music]

- I'm Andrew Huberman,

and I'm a Professor of Neurobiology and Ophthalmology

at Stanford School of Medicine.

Today, we continue our discussion of the senses.

And the senses we are going to discuss

are pain and pleasure.

Pain and pleasure reflect two opposite ends of a continuum,

a continuum that involves detection of things in our skin

and the perception, the understanding

of what those events are.

Our skin is our largest sensory organ

and our largest organ indeed.

It is much larger than any of the other organs in our body.

And it's an odd organ if you think about it,

it has so many functions.

It acts as a barrier between our organs

and the outside world,

it harbors neurons nerve cells that allow us

to detect things like light touch, or temperature

or pressure of various kinds.

And it's an organ that we hang ornaments on.

People put earrings in their ears.

People decorate their skin with tattoos and inks

and other things.

And it's an organ that allows us to experience

either great pain or great pleasure.

So it's a multifaceted organ and it's one

that our brain needs to make sense of in a multifaceted way.

So today we're going to discuss all that.

And most importantly, how you can experience more pleasure

and less pain by understanding these pathways.

We will also discuss things you can do,

and if you wish things you can take

that will allow you to experience more pleasure

and less pain in response

to a variety of different experiences.

Before I go any further,

I want to highlight a particularly exciting area of science

that relates to the skin and to sensing

of pleasure and pain,

but has everything to do with motivation.

Motivation is something that many people struggle with,

not everybody, but most people experience dips

and peaks in their motivation

even if they really want something.

How should we think about these changes in motivation?

What do they reflect?

Well at a very basic level, they reflect fluctuations

changes in the levels of a chemical called dopamine.

Most of us have heard of dopamine.

Dopamine is a neuromodulator meaning it modulates

or changes the way that neurons nerve cells work.

Most of us have heard that dopamine

is the molecule of pleasure.

However, that is incorrect.

Dopamine is a molecule of motivation and anticipation.

To illustrate how dopamine works,

I want to highlight some very important work

largely carried out by the laboratory

of a guy named Wolfram Schultz.

The Schultz Laboratory has done dozens

of excellent experiments on the dopamine system

and have identified something called

reward prediction error.

Although in some sense you can think about it

as reward prediction variance.

Changes in the levels of dopamine depending

on whether or not you expect a reward

and whether or not you get the reward.

So I'm going to make this very simple.

Dopamine is released into the brain and body

and generally makes us feel activated and motivated,

as if we have energy to pursue a goal.

And it is released into the brain and body

in anticipation of a reward.

Measurements of dopamine have been made

in animals and humans.

And what you find is that when we anticipate a reward,

dopamine is released,

we will put in the work to achieve that reward.

That work could be mental work or physical work,

but when the reward arrives,

dopamine levels drop back down to baseline.

That's right.

When we receive a reward,

dopamine levels go back down to baseline.

So the way to envision this as you can just imagine

a sort of increase in dopamine as we anticipate something

we're working towards it, we're working towards a goal.

We're excited about seeing somebody or meeting somebody

or receiving some reward and then the reward comes

and dopamine goes down.

Now that's all fine and good,

but there is a way to get much more dopamine

out of that process and therefore a way

to have much more motivation, energy, and focus

because those are the consequences of elevated dopamine.

The way to do that is to not deliver the reward

on an expected schedule.

So experiments have been done where there's an anticipation

of a reward, there's work,

and then the reward only arrives every other

or every third about of work, okay?

So this would be like getting a pat on the head.

If you're a dog or a, perhaps a child or an adult,

or getting a monetary reward only for every third project

or every third race that you win.

Pick any kind of goal.

It doesn't matter.

These molecules don't care about what you're pursuing.

They are a common currency of different types of activities.

That's a regular reward schedule,

and it will not alter the pattern of dopamine release

that I described before.

However, if the reward arrives intermittently

almost randomly, so you anticipate a reward

as a maybe it might come, it might come.

Then you work, work, work, work, work, no reward.

You repeat the work, work, work, work, work, work,

and then you get a reward.

So some trials, you do some trials, you don't,

and it's completely random.

Under those conditions, the amplitude,

the amount of dopamine that's released into your system

and the motivation to continue working hard

or playing whatever kind of game you're playing,

doubles or triples.

And this is the basis of things like slot machines

and gambling.

And this is why so many people will give so much

of their money up to casinos and the casinos always win.

Sometimes people walk away with more money

than they came to the casino with,

but the vast majority of the time,

the house wins as they say.

And it's because they understand

intermittent reward schedules.

And you can apply this to stay motivated

in your own pursuits.

Rather than thinking about the pleasure of a reward,

understand that dopamine is released in response

to anticipation reward, and that is the fuel for work.

And every once in awhile at random remove the reward.

That's the way to continue to stay motivated.

Not to reward every action or every goal.

And this is also true,

if you're trying to train up children or train up players

on a team, you should not celebrate every win.

I know that's a little counter-intuitive,

we're going to go more into the biology of dopamine

and how it relates to the pleasure system

later on in the podcast,

but for now understand intermittent reward schedules

harness the biology of dopamine in ways that can allow you

essentially infinite motivation over time.

Before I go any further,

I want to acknowledge that this podcast is separate

from my teaching and research roles at Stanford.

It is however, part of my desire and effort

to bring zero cost to consumer information

about science and science-related tools

to the general public.

In keeping with that theme, I'd like to thank the sponsors

of today's podcast.

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So let's talk about pleasure and pain.

I think we all intuitively understand

what pleasure and pain are.

Pleasure generally is a sensation in the body

and in the mind that leads us to pursue more

of whatever is bringing about that sensation.

And pain is also a sensation in the body and in the mind

that in general leads us to want to withdraw

or move away from some activity or interaction.

That's not always the case.

Some people actively seek out pain.

Some people somehow can't seem to engage with

or experience pleasure,

but most people operate on this basis of pleasure and pain.

Scientists would call this appetitive behaviors,

meaning behaviors that lead us to create an appetite

for more of those behaviors and aversive behaviors,

behaviors that make us want to move away from something.

The simplest example of that would be putting your

hand near a hot flame, at some point,

there would be a reflex or a deep desire

to withdraw your hand.

Tasting something delicious in general makes us want

to eat more of that thing.

Interactions with other people that we find delicious,

also make us want to interact with those people more.

None of this is complicated or sophisticated.

This is simply to illustrate the fact that pleasure and pain

tend to evoke opposite responses,

opposite behavioral responses

and opposite emotional responses.

So how does that come about?

Well, it really comes about by an interaction

that starts at one end of our body, meaning our skin

and the other end of the organs of our body,

which is deep within the brain.

So let's consider these two ends of the spectrum

of pleasure and pain and what they contribute

to those experiences of pleasure and pain.

The organ that we call the skin, as I mentioned earlier,

is the largest organ in our body.

And throughout that organ, we have neurons,

little nerve cells.

Now to be really technical about it,

and the way I'd like you to understand it

is that the so-called cell body meaning the location

of a cell in which the DNA and other goodies

the kind of central factory of the cell,

that actually sits right outside your spinal cord.

So all up and down your spinal cord on either side

are these little blobs of neurons,

little collections of neurons.

They have a name if you'd like to know

for you aficionado or those who are curious,

they're called DRGs dorsal root ganglia.

A ganglion is just a collection or clump of cells.

And those DRGs are really interesting because they send

one branch that we call an axon,

a little wire out to our skin, also to our muscles

into our organs, but here we're talking about the skin.

They send a wire out to our skin and that wire literally

reaches up into the skin.

It's actually in our skin and they have another wire

from that same cell body

that goes in the opposite direction,

which is up to our brain and creates connections

within our brain in the so-called brainstem.

What this means is that the neuron in your body

that we call the DRG that sends a wire an axon

to sense what's going on in your big toe

and then sends another axon in the opposite direction

into the base of your brain,

that is the largest cell in your entire body of any kind.

Fat cell, muscle cell, nerve cell, et cetera.

Is extremely long cells.

It can be a meter or more depending

on how tall you happen to be.

So we have these cells that have wires

they go off in two different directions

and the wire that's within our skin will respond

to any number of different categories of stimuli.

These wires are positioned within the skin

to respond to mechanical forces.

So maybe light touch,

some will only send electrical activity up

toward the brain in response to light touch.

Meaning if you press on the skin really hard,

they don't respond.

You stroke the skin lightly with your fingertips

or a feather and they respond very robustly.

Others respond to course pressure, the hard pressure,

but they won't respond to a light feather, for instance.

Others respond to temperature.

So they will respond to the presence of heat

or the presence of cold or changes in heat and cold.

And still others respond to other types of stimuli,

like certain chemicals on our skin.

Many of you have probably experienced the sensation

of eating a hot pepper.

Well, I don't recommend doing this,

but were you to take a little slice of jalapeno

or other hot pepper, habanero pepper or something like that

and rub it on your skin, you would actually feel something

at that location.

And that's because that pepper doesn't just create

a sensation within your mouth,

it will create a similar sensation on your skin.

So these neurons are amazing.

They're collecting information of particular kinds

from the skin throughout the entire body

and sending that information up toward the brain.

And what's really incredible,

I just want you to ponder this for a second.

What's really incredible is that the language

that those neurons use is exactly the same.

The neuron that responds to light touch

sends electrical signals up toward the brain,

the neurons that respond to cold or to heat

or to habanero pepper, they only respond

to the particular thing that evokes the electrical response.

I should say that they only respond

to the particular stimulus, the pepper,

the cold, the heat, et cetera,

that will evoke an electrical signal,

but the electrical signals are a common language

that all neurons use.

And yet, if something cold is presented to your skin,

like an ice cube, even if you don't see that ice cube,

if your eyes are closed, or someone comes up behind you

and puts an ice cube against your bare skin back,

you know that that sensation, that thing is cold.

You don't misperceive it as heat or as a habanero pepper.

So that's amazing.

What that means is that there must be another element

in the equation of what creates pleasure or pain.

And that element is your brain.

Your brain takes these electrical signals

and interprets them.

Partially based on experience,

but also there are some innate meaning some hard wired

aspects of pain and pleasure sensing

that require no experience whatsoever.

A child doesn't have to fall down but once

to know on that first fall, that hurt.

They don't have to touch a flame,

but once and the very first time they will withdraw

their hand from the flame.

So no prior experiences required.

Other things prior experience is required.

For instance, if you're somebody that has

an intense, intense aversion to spicy foods,

that's probably because you've tasted spicy foods before.

Likewise, if you really like sweet foods,

it's probably because you've tasted them before.

So you can start to make predictions

based on prior experience,

but the pain and pleasure system

don't need prior experience.

What they need is a brain that can interpret

these electrical signals

that can take these electrical signals and somehow create

what we call pleasure and pain out of them.

So what parts of the brain?

Well, mainly it's the so-called somatosensory cortex.

The portion of our neocortex,

which is on the outside of our brain,

that kind of bumpy part, not kind of

if you have a normally formed brain, it will be bumpy.

If you have a smooth brain that's not good.

Some animals just have a smooth brain.

Humans have a bumpy brain,

which means it has a very large surface area.

And those bumps are 'cause you squeezed it like a pizza

and clump and you bunched it all up

and put inside the skull.

That's good.

That means you have a lot of neurons.

And in your somatosensory cortex,

you have a map of your entire body surface.

That map is called a homunculus.

And if we were to take your cortex

and lay it out on a table,

I've actually done this with the cortices

of various animals and humans included.

What you would find is that there's literally a map

of your entire body surface.

But it wouldn't look exactly like you,

this map would be very distorted.

Why would it be distorted?

Well, certain areas of your body

have a much denser innervation as we call it,

or put simply many more of these sensory wires

from these DRGs within your skin.

So this map of you that exists in your brain,

and you do have one of these on each side of your brain,

so you have two of these maps to homunculi,

that is you, it's your representation of touch

including pleasure and pain.

And in that map, your lips are enormous.

And your back is very, very small.

And the area around your eyes

and the area representing your face is absolutely enormous.

So you would look like some sort of odd, weird clay doll

from some sort of bizarre late night animation thing.

And just imagine the psychedelic experience of that

character of you and that's what it would look like.

But it's not randomly organized.

To the contrary, it's highly organized

in a very particular way,

which is that the areas of your skin

that have the highest density of the sensory receptors

are magnified in your brain.

So it's sort of like having more pixels

in a certain part of a camera than others,

and in doing that allowing higher resolution

in this case of touch, not a vision,

but of touch sensation in certain parts of your body.

What are the areas that are magnified?

Well, the lips, the face, the tips of the fingers,

the feet, and the genitals.

And so this map of you has very large lips, face,

tips of fingers, bottoms of feet, and genitals.

And that's because the innervation,

the number of wires that go into those regions of your body

far exceeds the number of wires for sensation of touch

that go to other areas of your body.

You can actually experience this in real time right now

by doing a simple experiment that we call

two-point discrimination.

Two-points discrimination is your ability

to know whether or not two points of pressure

are far apart, near each other,

or you actually could perceive incorrectly

as one point of pressure.

You might want a second person to do this experiment.

Here's how you would do it.

You will close your eyes,

that person would take two fine points.

Don't make them too sharp, please.

So it could be two pencils or pens or the backs of pens.

Two pens I'm holding in my hands.

If you're just listening to this, I'm just holding two pens.

My favorite pens, these pilot, V5 or V7, which I love.

If you were to close your eyes

and I were to take these two pens

and put their points close together about a centimeter apart

and present them to the top of your hand,

I'm going to just going to do that now to myself.

You, even though your eyes were closed,

you would be able to perceive that that was two points

of pressure presented simultaneously

to the top of your hand.

However, if I were to do this to the middle of your back,

you would not experience them as two points of pressure.

You would experience them as one single point of pressure.

In other words, your two point discrimination is better,

is higher on areas of your body

which have many, many more sensory receptors.

You are more sensitive at those locations.

Now this makes perfect sense once you experience it

or you hear about it.

However, most of us don't really appreciate

how important and what a profound influence this change

in density of receptors across our body surface has.

And we can go a step further and describe another feature

of the way that you're built and the way

that you experience pleasure and pain,

which is called the dermatome.

The dermatome is literally the way

in which your body surface is carved up

into different territories.

Much like a map of the United States is carved up

into different territories

of states and counties, et cetera.

The dermatome is the way in which neurons

connect to different parts of your body.

Now, you've actually experienced the dermatome before.

The dermatome is when you have a neuron

that connects to a particular area of the body

and that neuron doesn't just send one little wire out

like one little line and go up into the skin

to detect mechanical, or thermal, or chemical stimuli.

It actually sends many branches out like a tree.

But remember those branches of the tree come

from one single neuron.

Now, occasionally what will happen is you will experience

something like cold, or heat, or pain, or tingling

on a patch of your body.

And occasionally that patch of body will actually have

a very cleanly demarcated boundary,

a very stark boundary with the areas around it.

A good example of this would be the herpes simplex 1 virus,

which if one has this virus,

and I should mention that somewhere between 80 and 90%

of people have this virus,

this is not a sexually transmitted virus.

This is a virus is transmitted very easily between people

through various forms of contact non-sexual contact,

it's present in children, it's present in adults

and most people get it, some get symptoms and some don't

some get recurring symptoms, some don't.

We can talk about that at the end, if you like,

but this virus lives on what's called

the fifth cranial nerve also called the trigeminal nerve.

The trigeminal nerve sends branches out to the lips,

to the eyes, and to certain portions of the face.

So for those of you listening,

I've just kind of put my right hand across my face

and to sort of simulate the three branches,

the trigeminal aspect of this nerve.

So tri three.

Now, when the herpes virus flares up, as they say,

in response to stress or other factors,

the virus inflames that nerve

and people experience tingling and pain on the nerve.

Sometimes they'll get a cold sore or a blister

on their lip or near their mouth,

sometimes they'll get a collection of those.

And that's because that dermatome is actually inflamed.

Now other people will experience something like shingles.

It's a fairly common viral infection.

And what they'll notice is they'll get a rash

that has a boundary.

It's like, they'll get a bunch of bumps,

sometimes blisters, and it'll have a sharp boundary.

That boundary exists because the virus exists on the nerve.

And so it actually is boundaried

with the neighboring area of the body

that's receiving input from another nerve

and that one doesn't have the virus living on it.

So anytime you see a rash or a pattern on the body surface

on the skin that has a pretty stark boundary,

chances are that's an event that's impacting the dermatome.

I've experienced this before

then not through herpes simplex,

but through the experience of having a lot of blood

sort of aggregating in a kind of a segment

across the front of my face, it was really bizarre.

I looked in the mirror and I thought, what is going on here?

I was having an allergic reaction to something I'd eaten.

And that allergic reaction clearly was affecting one

of the nerves and therefore the dermatome

and what it showed up was,

it was almost like someone had drawn lines on my face

that said, okay, this rash or this reaction rather

can happen here, but not in a region right next to it.

Whenever you see that chances are

it's a reaction of the nerves of the dermatome.

So you'll start to see these things more and more

when you start to look for them.

You don't always have to have a viral infection

to experience this.

Sometimes you'll just experience tingling

or even a pleasant sensation,

and it will be restricted in kind of a strict boundary

on one location or your body surface and not another.

Not corresponding to an organ like,

okay, this arm or just your feet or something like that.

But just a segment.

It's almost like someone outlined a particular area

of her body surface.

That's the dermatome.

So you've got sensors in the skin

and you've got a brain that's going to interpret

what's going on with those sensors.

In fact, we can take an example of a sudden rash

or inflammation at one location, the dermatome,

and we can ask what would make it hurt?

What would make it worse?

What would make it go away?

And believe it or not, your subjective interpretation

of what's happening has a profound influence

on your experience of pleasure or pain.

There are several things that can impact these experiences,

but the main categories are expectation.

So sort of whether or not you thought or could expect

that this thing was going to happen, right?

If someone tells you this is going to hurt,

I'm going to give you an injection right here,

it might hurt for a second.

That's very different and your experience of that pain

will be very different than if it happened suddenly

out of the blue.

There's also anxiety, how anxious,

or how high or low your level of arousal, autonomic arousal,

that's going to impact your experience of pleasure or pain.

How well you slept and where you are

in the so-called circadian or 24-hour cycle.

Our ability to tolerate pain changes dramatically

across the 24-hour cycle.

And as you can imagine is during the daylight waking hours

that we are better able to tolerate,

we are more resilient to pain,

and we are better able to experience pleasure.

At night our threshold for pain is much lower.

In other words, the amount of mechanical

or chemical or thermal meaning temperature stimulated

that can evoke a pain response and how we rate that response

is much lower at night.

And in particular, in the hours between 2:00 AM and 5:00 AM,

if you're on a kind of standard circadian schedule.

And then the last one is our genes.

Pain threshold and how long a pain response lasts

is in part dictated by our genes.

And later I'm going to discuss this myth

or whether or not it's really a myth

as to whether or not certain people in particular red heads,

people who have reg pigmented hair and fair skin,

whether or not their pain thresholds differ.

And to just give you a little sneak peek into that,

indeed they do and it's because of a genetic difference

in a particular gene, in a particular pattern of receptors

in the skin that are related to the pigmentation

of hair and skin.

So we have expectation, anxiety, how well we've slept,

where we are in the so-called 24-hour circadian time

and our genes.

So let's talk about expectation and anxiety

because those two factors can powerfully modulate

our experience of both pleasure and pain

in ways that will allow us to dial up pleasure if we like

and to dial down pain, if indeed that's what we want to do.

So let's talk about expectation and anxiety

because those two things are somewhat tethered.

There are now a number of solid experiments,

both in animal models and in humans

that point to the fact that if we know a painful stimulus

is coming, that we can better prepare for it mentally

and therefore buffer or reduce the pain response.

However, the timing in which that anticipation occurs

is vital for this to happen.

And if that timing isn't quite right,

it actually can make the experience of pain far worse.

So here I'm summarizing a large amount of literature,

but essentially if subjects are warned

that a painful stimulus is coming,

their subjective experience of that pain is vastly reduced.

However, if they are warned just two seconds

before that pain arrives, it does not help.

It actually makes it worse.

And the reason is they can't do anything mentally

to prepare for it in that brief two second window.

Similarly, if they are warned about pain that's coming

two minutes before a painful stimulus is coming

electric shock or a poke or cold stimulus or heat stimulus

that's pretty extreme, that also makes it worse

because their expectation ramps up the autonomic arousal.

The level of alertness is all funneled toward

that negative experience that's coming.

So how soon before a painful stimulus

should we know about it if the goal is

to reduce our level of pain?

And the answer is somewhere between 20 seconds

and 40 seconds is about right.

Now, I'm averaging across a number of different studies,

but if you have about 20 seconds or 40 seconds

advance warning that something bad is coming,

you can prepare yourself for that,

but the preparation itself and the arousal

that comes with it, the kind of leaning in,

okay, I'm either going to relax myself

or I'm going to really kind of dig my heels in

and kind of meet the pain head on.

That seems to be the optimal window.

This can come and useful in a variety of contexts,

but I think it's important because what it illustrates

is that it absolutely cannot be just the pattern of signals

that are arriving from the skin, from these DRGs,

these neurons that connect to skin

that dictates our experience of pain or pleasure.

There has to be a subjective interpretation component,

and indeed that's the case.

So let's talk about the range of pain experiences.

And from that, we will understand better

what the range of pleasure experiences are

that different people have because we are all different

in terms of our pain threshold.

First of all, what is pain threshold?

Pain threshold has two dimensions.

The first dimension is the amount of mechanical or chemical

or thermal stimulation that it takes for you or me

or somebody else to say, I can't take that anymore.

I'm done.

But there's another element as well

which is how long the pain persists.

I'll just describe myself for example,

I don't consider myself somebody

who has a particularly high pain threshold.

I don't think it's particularly low either,

but I wouldn't consider myself somebody

that has a particularly high pain threshold.

When I stubbed my toe against the corner of the bed,

it absolutely hurts.

But one thing that I've noticed is

that I have very sharp inflections, very high inflections

in my perception of pain, and then they go away quickly.

I don't know if that's adaptive or not.

It's probably not,

but my experience of pain is very intense, but very brief.

Other people experience pain in a much

kind of slower rising, but longer-lasting manner.

And to just really point out how varied we all are

in terms of our experience of pain,

let's look to an experiment.

There been experiments done at Stanford School of Medicine

and elsewhere, which involved having subjects

put their hand into a very cold vat of water

and measuring the amount of time

that they kept their hand in that water.

And then they would tell the experimenter very quietly,

how painful that particular stimulus was

on a scale of one to 10 so-called Likert scale

for your aficionados.

That simple experiment revealed that people experience

the same thermal in this case, cold stimulus,

vastly different.

Some people would rate it as a 10 out of 10 extreme pain.

Other people would rate it as barely painful at all,

like a one.

Other people, a three other people, a five, et cetera.

Now what's interesting is that the same thing is true

for experience of a hot, painful stimulus

120 degree hot plate, where you have to put your hand on it,

and then at some point you remove your hand.

Some people are able to keep their hand

on there the whole time, but people rate that experience

as very painful, a little bit painful

or moderately painful depending on who they are.

Now, that's interesting,

probably not that surprising, however,

but what is very interesting is that

when the same experiment was done on medical doctors

or medical doctors in training,

they too of course experienced pain

through a range of subjective experiences.

Some of them just like any other person off the street

said a particular stimulus of a particular temperature

was very painful, other said it wasn't painful at all

and some said it was moderately painful.

And that turns out to be vitally important

for the treatment of pain

because pain is not an event in the skin.

Pain is a subjective, emotional experience.

You may have heard that we have a particular category

of these DRGs that innervate the skin,

which are called nociceptors.

Nociceptor comes from the word noci, nocere I believe it is,

which means to harm.

However, nociceptors don't carry information about pain,

they carry information about particular types of stimuli

impacting the skin.

And then the brain assigns a value of valence to it,

a label and says that's painful.

And where people draw the line between not painful

and painful varies.

Now, because physicians are people

and because physicians treat pain,

what we know from a lot of data now is that if someone comes

into the clinic and says they're experiencing chronic pain

or whole body pain or acute pain after an injury

or one location, it doesn't really matter what the cause is

or even if there's a cause at all,

how the doctor reacts to that report of the patient's pain

will dictate in many cases the course of treatment.

And of course doctors, their goal is to treat the patient

to going to the patient's needs, not their own.

And that's what good doctors do.

However, it's been found and I think now there is work

being done to try and change this,

but if a doctor has a very high threshold for pain,

their interpretation of somebody else's report of pain

is going to be different.

They might not discount the patient, right?

This doesn't necessarily mean that they think, oh,

this person their pain is irrelevant, probably not.

In fact, from having a high threshold for pain,

if someone comes in and says, I'm in extreme pain,

that doctor probably thinks,

wow, this has to be really, really extreme,

but they can be talking about two different experiences.

Similarly, if a physician has a very low threshold for pain,

and someone comes in and says,

yeah, I'm experiencing some pain in my back.

I've got the sciatica thing, but yeah,

it's a little bit uncomfortable.

It's like a, I don't know like a four out of 10.

Well, that physician might interpret that four out of 10

as a pretty extreme sense of pain

or pretty extreme experience of pain.

And so you can start to see how the subjective nature

of pain can start to have real impact

on the treatment of pain because treatment of pain

is carried out by physicians.

In fact, there is no objective measure of pain.

We can ask how long somebody can keep their hand

on a hot plate or in a cold bath.

You can do various experiments.

They even have some extreme experiments

where they'll shave a portion of the leg

and they'll put on a very painful chemical compound

and see how long people can tolerate that.

These are very uncomfortable experiments as you can imagine,

but in general, we don't have a way

of measuring somebody else's subjective experience of pain.

There is no blood pressure measure.

There's no heart rate beats per minute measure of pain.

So one of the great efforts of neuroscience

and of medicine is to try and come up

with more objective measures of pain.

Similarly, pleasure is something that we all talk about.

Ooh, that feels so good, or I love that

or more of that please or less of that,

but we have no way of gauging what other people

are experiencing except what they report through language.

And so this is really just to illustrate

that this whole thing around pain isn't a black box.

We do have an understanding of the elements.

There are elements in the skin,

there's elements of the brain,

there's expectation, anxiety, sleep, and genes,

but that it is very complicated.

And yet there are certain principles

that fall out of that complicated picture

that can allow us to better understand and navigate

this axis that we call the pleasure-pain axis.

So rather than focus on just the subjective nature of pain,

let's talk about the absolute qualities of pain

and the absolute qualities of pleasure

so that we can learn how to navigate those two experiences

in ways that serve us each better.

First of all, I want to talk about heat and cold.

We do indeed have sensors in our skin

that respond to heat and cold.

And for any of you that have entered a cold shower

or a cold body of water of any kind or ice bath, et cetera,

you will realize that getting into cold is much harder

if you do it slowly.

Now, despite that people tend to do it very slowly.

I have noticed an enormous variation with which people

can embrace the experience of cold.

I noticed it because I do some work with athletes

and I do some work with military

and I do some work with the general public.

And one of the best tests of how somebody can handle pain

is to ask them to just get into an ice bath.

It's not a very sophisticated experience,

but it really gets into the core of the kind of circuitry

that we're talking about, both in the skin and in the brain.

Some people regardless of sex, regardless of age,

and regardless of physical ability

can just get into the cold.

They're somehow able to do it.

Now, I don't know what their experience of the cold is.

And neither do you.

You only know your experience,

but they're able to do that.

Some do it quickly, some do it slowly.

Others find the experience of cold to be so aversive

that they somehow cannot get themselves in.

They start quaking, they start complaining

and many of them just simply get out.

They can't do it.

Some don't even get in past their knees.

This isn't necessarily about pain threshold,

but it's related to that.

I think it can be helpful to everyone to know

that even though it feels better at a mental level

to get into the cold slowly and people ask, oh,

I just want to get in slowly, I want to take my time.

It is actually much worse

from a neuro-biological perspective.

The neurons that sense cold respond

to what are called relative drops in temperature.

So it's not about the absolute temperature of the water.

It's about the relative change in temperature.

So as you move from a particular temperature,

whether or not it's in the air next to an ice bath

or cold shower, or from a body of water that's warm

to a body of water that's colder,

or sometimes in the ocean, you'll notice it's warm.

And then as you swim out further,

you'll get into a pocket of water where it's much colder.

That's when the cold receptors in your skin start firing

and sending signals up to your brain.

Therefore, you can bypass these signals going up

to the brain with each relative change one degree change,

two degrees change, et cetera,

by simply getting in all at once.

In fact it is true and maybe you've been told this before,

and it is true that if you get into cold water

up to your neck,

it's actually much more comfortable

than if you're halfway in and halfway out.

And that's because of the difference in the signals

that are being sent from the cold receptors

on your upper torso,

which is out of the water in your lower torso.

Now, I wouldn't want anyone to take this

to mean that they should just jump

into an unknown body of water.

There are all sorts of factors like currents,

and if it's very, very cold, yes, indeed.

You can stop the heart.

People can have heart attacks from getting

into extremely cold water, like a melted mountain stream

that's been frozen all winter,

or has been very, very cold or as a snow pack going into it.

If very cold, you can indeed have a heart attack.

So please be smart about how cold and what bodies

of cold water you happen to put yourself into.

But it is absolutely true that provided it safe,

getting into a cold water is always going to be easier

to do quickly and is going to be easier

to do up to your neck.

In fact, you actually want to get your shoulders submerged.

There are a number of other things you can do

if you really want and it's safe to do.

You can put your face under and activate

the so-called dive reflex, which also makes the tolerance

of cold easier believe it or not.

So it's very counterintuitive.

It's like getting into water faster and more completely

you will experience as less uncomfortable, less cold.

And indeed that's the case.

And that's because these cold receptors

are measuring every relative drop in temperature.

So every single one is graded as we say in biology,

it's not absolute.

As an additional point, if you're sitting in a body

of cold water and it's not circulating,

you'll notice that you start to warm up a little bit.

Or even if you feel like you're freezing cold,

if you move and that water around you moves, of course,

then you'll notice it's got even colder.

And that's because there's a thermal layer.

You're actually heating up the water

that surrounds your body

like a halo around every aspect of your body.

A sort of silhouette of you of heat

where you're heating that water.

When you move, you disrupt that thermal layer.

Now heat is the opposite.

Heat and the heat receptors in your skin

respond to absolute changes in temperature.

And this is probably because our body

and our brain can tolerate drops in temperature

much better than it can tolerate

increases in temperature safely.

So when you move from say a standard outdoor environment,

I mean, here in the States

we measure in terms of Fahrenheit.

So maybe it's a 75 or an 80 degree, or even 90 degree day,

and you get into a 100 degrees sauna,

or if you're in a cool air conditioned building

and you go outside and it's very warm outside,

you sort of feel like the heat hits you all at once, boom.

Hits you all at once, kind of like a slap in the face,

but then it will just stay at that level.

Your body will acclimate to that particular temperature.

However, if that temperature is very, very high,

you'll notice that your experience of that heat

and your experience of kind of pain and discomfort

and your desire to get out of that heat

will tend to persist.

You don't really adapt in the same way.

And certain people who are really good

at handling very hot sauna, get better at this.

You learned to calm your breathing, et cetera,

lower your autonomic arousal.

Obviously you don't want to let your body temperature

go too high because neurons cook, they die.

If neurons die, they don't come back and that's bad.

Many people unfortunately harm themselves with hyperthermia.

Everyone has a different threshold for this, but in general,

you don't want your body temperature to go up too high.

That's why a fever of like 103 starts

to become worrisome 104.

You really get concerned if and it goes

up into that range or higher,

that's when you need to really cool down the body

or get to hospital so they can cool you down.

Heat is measured in absolute terms by the neurons.

So gradually moving into heat makes sense,

and finding that threshold,

which is safe and comfortable for you,

or if it's uncomfortable,

at least resides within that realm of safety.

So that's heat and cold,

and those are sort of non-negotiables.

You can try and lower your level of arousal.

In fact, many people who get into a cold shower

and ice bath I think the recommendation

that I always give is that

you have two possible approaches to that.

You can either try and relax yourself,

kind of just stay calm within the cold,

or you can lean into it.

You can actually take mental steps

to generate more adrenaline

to kind of meet the demands of that cold.

And at some point we'll do a whole episode on

how to use cold and heat to certain advantages

we've done a little bit of this in past episodes

using the cold to supercharge human performance

and things of that sort.

But in general, cold is measured in relative terms.

And therefore getting in all at once is a good idea provided

you can do it safely.

And heat is measured in absolute levels

by your brain and body and therefore

you want to actually move into it gradually.

So it's the kind of the inverse of what you might think.

One of the most important things to understand

about the experience of pain and to really illustrate

just how subjective pain really is,

is that our experience of pain and the degree of damage

to our body are not always correlated.

And in fact, sometimes can be in opposite directions.

A good example of this would be x-rays.

We all occasionally get x-rays at least in the US

we get x-rays when we go to the dentist from time to time,

and the occasional x-ray might be safe

depending on who you are

provide you're not pregnant, et cetera.

I've gone to the dentist.

They put you in the chair,

they cover you with the lead blanket,

and then they run behind the screen to protect themselves.

And they beam me with the x-rays to get a picture

of your teeth and your jaws and your skull, et cetera.

Well, if you were to get too many x-rays,

you could severely damage the tissues of your body,

but you don't experience any pain during the x-ray itself.

In contrast, you can think that your body is damaged

and experienced extreme pain

and yet your body can have no damage.

A classic example of this was published

in the British Journal of Medicine,

in which a construction worker fell from

I think it was a second story, which he was working

and a nail went up and through his boot

and he looked down and he saw the nail going

through his boot and he was in absolute excruciating pain.

They took him to the hospital and because the nail was

so long and because of where it had entered,

it exited the boot, they had to cut away the boot

in order to get to the nail.

And when they did that,

they revealed that the nail had passed

between two of his toes.

It had actually failed to impale his body in any way.

And yet the view, the perception of that nail

entering his boot at one end and exiting the boot

at the other was sufficient to create the experience

of a nail that had gone through his foot.

And the moment he realized that that nail had not gone

through his foot, the pain completely evaporated.

And this has been demonstrated numerous times.

People that work in emergency rooms

actually see variations on this.

Not always that extreme,

but many times what we see and how we perceive that wound

or that event has a profound influence

on how we experience pain.

And I mentioned this, not just because it's a

kind of sensational and fantastic example

of this extreme, subjective nature of pain,

but also because it brings us back to this element

which is, we don't know how other people feel.

Not just about pain, but about pleasure.

We think we do, we have some general sense

of whether or not an event ought

to be painful or pleasurable,

but actually we barely understand how we feel

let alone how other people feel,

and we can be badly wrong about how we feel

meaning we can misinterpret our own sense of pain

or our own sense of pleasure depending on what we see

with our eyes and what we hear with our ears.

So we hear a scream like a shrill scream,

and we think it must be pain.

And if we look at something that's happening to somebody

and it fits a prior category or a prior representation

of what we would consider painful stimulus,

well, then we think that they're an extreme pain,

but actually they might not be in pain at all.

Now this highly subjective nature of pain

and the way in which we use our visual system

to interpret other people's pain and our own pain

has actually been leveraged to treat a very extreme form

of chronic pain.

And it's an absolutely fascinating area

of biology and neuroscience.

And it's one that we can actually all leverage

toward reducing our own levels of pain

whenever we are injured.

Or believe it or not, even in chronic pain.

To describe this area of science requires

a kind of extreme example,

but I want to be clear that even if you don't suffer

from this extreme example,

there's relevance and a tool to extract for you.

The extreme example is that of an amputated digit,

meaning one of your fingers or your toes,

or of an amputated limb.

So people that have digits or limbs that are gone missing

from an injury or surgical removal,

will often have the experience that it's still there.

The so-called phantom limb phenomenon.

Now, why would that be?

Well, when you remove a particular finger or limb,

obviously that finger and limb is gone

and the dorsal root ganglion neuron

that would normally send a wire out

to that particular region of the body,

that wire is no longer there because that portion

of the body is no longer there.

And in some cases, those neurons die

almost always, but not always.

However, the map your so-called homunculus,

your representation of yourself in the brain is still there.

And this map, the so-called homunculus map

that you have in that I have is very plastic.

It can change.

And so as a consequence areas of the map

that adjacent to one another

can actually start to invade other areas of the map.

So for instance, there are neuroimaging studies

that have documented that somebody

that has say a complete removal of their left arm,

the representation of their left arm still exists

in the cortex.

And experimentally if one is to stimulate

that area of the cortex, that person,

and if that person were you,

would experience having that arm

that it were being stimulated, even though it's not there.

Now, someone who has an amputated arm doesn't need

to have their brain stimulated

in order to have the experience

of that phantom limb being present.

In fact, many people who have limbs that were amputated

feel as if that limb is still present

even though obviously it's not.

And no matter how many times they look to the stump

and just see a stump, somehow it doesn't reorganize

that homunculus so-called central brain map.

Now, that would be fine.

You might even think that would be better,

better to think you have the arm there

than to feel as if it's missing,

and yet many people who have amputated limbs

report phantom limb pain.

They don't feel that the arm

is just casually draped next to them.

They feel as if it's bunched up and it's an extreme pain.

In fact, this kind of contorted stance

that I'm taking right here in my chair

is not unlike the way that these patients described this.

They feel as if it's kind of cramped up,

it's very uncomfortable for them.

Now, and absolutely creative

and you could even say genius scientists

by the name of Ramachandra.

That's actually his last name,

his complete name is a little bit more complicated.

So you all almost always hear Ramachandran referred to as

Ramachandran or V.S Ramachandran because his full name

is Vilayanur Subramanian Ramachandran.

So a lot of letters in there, a lot of vowels,

but Ramachandran is a neuroscientist.

He was actually a colleague of mine

when my lab was formerly

at the University of California, San Diego.

Has done a lot of work on this phantom limb phenomenon.

And Ramachandra actually started off as a vision scientist.

And he understood the power of the visual system

in dictating our experience

of things like pain and pleasure.

And so what he developed was a very low technology

yet neuroscientifically sophisticated treatment

for phantom limb.

It consisted of a box, literally a box

that had mirrors inside of it.

And the patient would put the intact hand or limb

into one side,

and obviously they couldn't put the amputated limb

into the other side, but because of the configuration

of the mirrors, it appeared as though they had

two symmetric limbs inside the box.

And then he would have them look at that limb

and move it around.

And as they would do this,

they would report real time movement,

or I should say real time perception of movement

in the phantom limb.

Now this is absolutely incredible but makes total sense

when you think about the so-called top down

or contextual modulation of our sensory experience,

remember it's anticipation, it's anxiety,

it's interpretation of what's happening

that drives our perception of what's happening.

And so, as he would have these patients

move their intact limb to a more relaxed position,

the patients would feel

as if the phantom limb were relaxing.

And this was used successfully to treat phantom limb pain

in a number of different people.

It didn't always work.

And you can imagine sometimes

it might be a little trickier like for a leg

although there have been leg boxes that have been developed

and arranged for this purpose.

And what was remarkable is that they could finish

these experiments and have the patient, the person

enter a state of relaxation,

reduced the pain in the phantom limb,

and it would stay there even though, of course,

as they exited the mirror box,

they would go about their life and use their intact limb

for its various purposes.

I love this experiment because it really speaks

to the subjective nature of pain and pleasure.

It speaks to the power of the visual system,

like what we see just like the nail

through the boot experiment.

What we see profoundly impacts our experience

of pleasure and pain in this case pain.

Now, there's another aspect to the phantom limb experience

and of these maps, the so-called homunculus maps

in the cortex that Ramachandran worked on,

which has very interesting and reveals the degree

to which these maps are plastic or can change

in response to experience.

Turns out that because of the locations

of different body part representations within these maps,

certain parts of our body that normally we don't think of

as related can start to create merged experiences.

What do I mean by that?

Well, Ramchandran described a patient

who had a somewhat odd experience of having lost their foot.

So they actually had their foot amputated

about midway up the Achilles.

So lower portion of the calf and foot.

I don't recall what the reason was for having it removed.

And fortunately for this patient,

they did not experience pain in that portion of their body,

but rather they confided in him

that whenever they would have sex,

they would experience their orgasm in their phantom foot

in addition to in their genitals, of course.

And Ramachandra understood the homunculus map.

And he understood that this was because the representation

of the foot within the homunculus actually lies adjacent to,

and is somewhat interdigitated with

it actually kind of merges with the representation

of the genitalia.

Now that's a weird situation.

And yet you now know that the density of innovation

of the feet and the genitalia,

as well as the lips and the face are actually

the highest sensory innervation

that you have in your entire body.

And this speaks to, I think,

a more important general principle for all people

of the experience of pleasure or pain,

which is that an aspect of our pain or pleasure

can be highly localized.

It can be because of a cut to a particular location

on the body or it can because of a fall injury

or a kind of bruise on one side of our body.

And yet our experience of pleasure and pain

can also be an almost a body-wide experience.

And yet it's always most rich.

It's always most heightened in these regions of our body

that have dense sensory innervation.

So we experience pain and pleasure according

to local phenomenon receptors in the skin,

and this homunculus map

that has all these different territories,

but because of the way that those territories are related,

this kind of wild example of somebody experiencing orgasm

in their phantom foot speaks to the larger experience.

The more typical rather experience that I should say

that all people have,

which is that pleasure can be body-wide

or we can experience it in our face

or the bottoms of our feet and other areas of the body

that we experience pleasure and similarly with pain.

And that brings us to the topic of whole body pain,

not just localized pain, as well as whole body pleasure

not just localized pleasure.

There are a number of examples of whole body pain

that people suffer from.

And one common one is called fibromyalgia.

I want to just first share with you a little bit

of medical insight.

A few months back, I did an Instagram live

with Dr. Sean Mackey who's an MD medical doctor

and a PhD at Stanford School of Medicine

that was recorded and placed on my Instagram.

If you want to check it out,

we can provide a link to that in the show notes.

Dr. Mackey is the Chief of the Division of Pain

at Stanford School of Medicine.

So he's a scientist.

He studies pain and he treats patients dealing

with various forms of pain, whole body pain,

like fibromyalgia, acute pain, et cetera.

And he shared with me something very interesting,

which is that anytime you hear or see the word syndrome,

that means the medical establishment does not understand

what's going on.

A syndrome is a constellation of symptoms

that point in a particular direction

or some general set of directions about

what could be going on,

but it doesn't reveal a true underlying disease necessarily.

It could be aggregative diseases

or it could be something else entirely.

And I want to make sure that I emphasize

the so-called psychosomatic phenomenon.

I think sometimes we hear psychosomatic

and we interpret that as meaning all in one's head.

But I think it's important to remember

that everything is neural,

whether that's pain in your body

'cause you have a gaping wound

and you're hemorrhaging out of that wound

or whether or not it's pain for which you cannot explain it

on the basis of any kind of injury.

It's all neural.

So saying body, brain, or psychosomatic

it's kind of irrelevant.

And I hope someday we move past that language.

Psychosomatic is interesting.

There was a paper that was published in 2015,

and then again in 2020 a different paper

focused on the so-called psychogenic fevers

or psychosomatic effects.

I just briefly want to mention this

because it relates back to pain.

These studies have shown that there are areas

of the so-called thalamus,

which integrates and filter sensory information

of different kinds.

And within the brainstem, an area called the DMH

and I can also provide a link to this study if you like,

that shows that there is a true neurological basis.

There are brain areas and circuits that are related to

what's called psychogenic fever when we are stressed.

And in particular, if we think that we were injured

or that we were infected by something,

we can actually generate a true fever.

It is not an imagined fever.

It is our thinking generating

an increase in body temperature.

And so this has been called psychosomatic.

It's been called psychogenic, but it has a neural basis.

So when we hear syndrome and a patient comes into a clinic

and says that they suffer for instance,

from something which is very controversial frankly

like chronic fatigue syndrome,

some physicians believe that it reflects

a real underlying medical condition, others don't.

However, syndrome means we don't understand.

And that doesn't mean something doesn't exist.

Fibromyalgia or whole body pain for a long time

was written off or kind of explained away

by physicians and scientists frankly, my community

as one of these syndromes.

It couldn't be explained.

However, now there is what I would consider

and I think others would and should consider

from understanding of at least one of the bases

for this whole body pain.

And that's activation of a particular cell type

called glial.

And there's a receptor on these glial

for those of you that want to know called the toll 4 receptor

and activation of the toll 4 receptor is related

to certain forms of whole body pain and fibromyalgia.

Now, what treatments exist for fibromyalgia.

And even if you don't suffer from fibromyalgia,

and even if you don't know anyone who does

this is important information

because what I'm about to tell you relate

to how you and your body, which is you of course

can deal with pain of any kind.

And there are actually things that one can do and take

that can encourage nerve health in general.

In other conditions like diabetic neuropathy,

but in all individuals.

So there are clinical data using a prescription drug.

This is work that actually was done

by Dr. Mackey and colleagues.

The drug is called naltrexone.

Naltrexone is actually used for the treatment

of various opioid addictions and things of that sort,

but it turns out that a very low dose,

I believe it was a one 10th the size of the typical dose

of naltrexone has been shown to have some success

in dealing with and treating certain forms of fibromyalgia.

And it has that success because of its ability

to bind to and block these toll four receptors on glial.

So this so-called syndrome or this thing that previously

was called a syndrome, fibromyalgia

actually has a biological basis.

It was not just inpatients heads.

And I really tip my hat to the medical establishment

including Dr. Mackey and others

who explored the potential underlying biologies

of things like fibromyalgia and are starting

to arrive at treatments.

Now, I'm not a physician, I'm a professor,

so I'm not prescribing anything.

You should talk to your doctor of course,

if you have fibromyalgia or other forms of chronic

or whole body pain to explore whether or not these low dose

naltrexone treatments are right for you.

But I think it's a beautiful case study if you will,

not a case study of an individual patient,

but a case in study of linking up the patient's self-report

of these experiences and using science

to try to establish clinical treatments.

There's another treatment,

or I should say there's another approach

that one could take.

And again, I'm not recommending people do this necessarily.

You have to determine what's right and say for you,

I cannot do that.

There's no way your situation's very far too much,

and it would be outside of my wheelhouse

to prescribe anything, but there's a particular compound

which in the United States is sold over the counter

and in Europe is prescription.

It's one that I've talked about on this podcast before

for other purposes.

And that compound is acetylcarnitine.

Acetylcarnitine as I mentioned is by prescription

in most countries in Europe

and the US you can buy this over the counter.

There is evidence that acetylcarnitine can reduce

the symptoms of chronic whole body pain

and other certain forms of acute pain

at dosages of somewhere between one to three

and sometimes four grams per day.

Now acetylcarnitine can be taken orally.

It's found in 500 milligram capsules,

as well as by injection.

By injection in the States in the United States that is

also requires a prescription

or requires a prescription I should say.

The over-the-counter forms are generally capsules

or powders.

Those apparently do not require a prescription.

There are several studies exploring acetylcarnitine

in this context, as well as for diabetic neuropathy.

And what's interesting about acetylcarnitine is it's one

of the few compounds that isn't just used

for the treatment of pain,

but has also been shown in certain contacts

to improve peripheral nerve health generally.

And for that reason, it's an interesting compound.

I've also talked about acetylcarnitine on here previously,

because it has robust effects on things like spur motility

and health, including the speeds at which sperms swim,

how straight they swim turns out that swimming

for sperm is more efficient if they swim straight,

as opposed to like those kids in on the swim team,

they're like banging up against the lane lines

and zigzagging all over the place.

So it does turn out to be the case that the quickest route

between any two places is a straight line

and the good sperm know that,

and the less good sperm don't seem to know that.

And acetylcarnitine seems to facilitate straight swimming

trajectories as well as speed of swimming

and overall sperm health.

And there is evidence from quality peer reviewed studies

showing that acetylcarnitine supplementation can also be

beneficial for women's fertility in ways that it affects

perhaps we don't really know the mechanism,

health and status of the egg or egg implantation.

There are a large number of studies on acetylcarnitine.

You can look those up on Pub Med, if you like,

or on examine.com.

There are some studies that I don't think

are included there which are particularly interesting.

One that I just would like to reference the last name

of the first author is Mahdavi M-A-H-D-A-V-I.

The title of the paper is

Effects of l -Carnitine Supplementation

on Serum Inflammatory Markers

and Matrix Metalloproteinases Enzymes

in Females with Knee Osteoarthritis.

So this is a randomized double blind placebo controlled

pilot study that showed really interesting effects

of short term supplementation of acetylcarnitine.

Longer term, the effects were less impressive.

So it's pretty interesting that this compound has

so many different effects.

How could it have these effects?

Well, it appears that it's having these effects

through its impact on the so-called inflammatory cytokines.

Inflammatory cytokines for those of you that don't know

are secreted by the immune system

in response to different stressors,

physical stressors, mental stressors too

food that you eat that isn't good for you.

The so-called hidden sugars.

Yes, will increase inflammation

if they're ingested too often,

or in amounts that are too high in quantity.

Things like Interleukin 1 beta,

things like C-reactive protein,

things like interleukin 6.

Interleukin 6 is kind of the generic inflammatory marker

that all studies refer to.

And yet there are other interleukins,

please note that there are other interleukins

like interleukin 10 that are anti-inflammatory.

So immune system can secrete inflammatory molecules

to deal with wounds and stress and things.

And in the short term that's good,

and in the longterm that's bad.

And it can secrete anti-inflammatory cytokines like IL10.

And these matrix metalloproteinases,

it's kind of a mouthful,

but these matrix metalloproteinases are very interesting.

Anytime you see A-S-E, ASE that's generally an enzyme,

which means that these compounds in this case,

these matrix metalloproteinases are used

to break down certain elements around wounds

and scoring which might sound like a bad thing,

but in some cases is good because it allows certain cells

like glial cells so-called microglia

to come in like low ambulances,

like low paramedics and clean up wounds.

So scarring and inflammation

is kind of a double-edged sword.

It can be good, but too much scarring.

If it contains a wound too much,

doesn't allow the infiltration of cell types

to move in and take care of that wound and heal it up.

So it appears that L-carnitine is impacting a number

of different processes, both to impact pain

and perhaps, and I want to underscore perhaps,

but there are good studies happening now,

perhaps accelerate wound healing as well.

As long as we're talking about acute pain

and chronic pain and supplementation

and non-prescription drugs, at least in the United States

that people can take to deal with pain of various kinds,

I'd be remiss if I didn't mention the two

that I get asked most often about,

which are agmatine and S-adenosyl-L-methionine,

which is sometimes called SAMe.

Both of those have been shown to have some impact

categorized on examine as notable impact

on various forms of pain, due to osteoarthritis,

or due to injury of various kinds of indifferent subject

population, men, women, people of different ages, et cetera.

SAMe in particular has been interesting

because it's been shown head to head

with drugs like Naproxen and other drugs of that sort,

which are well established and sold over the counter

in the US to work at least as well

as some of those compounds at certain doses.

But it's also shown that SAMe

and some of those things take more time

in order to have those effects.

In fact, head to head with things like Neproxin

have been shown that they can take up to a month

in order to have the pain relieving effect.

Now, whether or not that makes them a better choice

or a worst choice really depends on your circumstances.

I'm certainly not recommending that anybody take anything,

but I do think it's interesting and important to point out

that things like agmatine, things like SAMe

have been shown under certain circumstances

to be beneficial for pain and they are outside the realm

of prescription drugs.

I think this is a growing area of

some people call them supplements,

some people call them nutraceuticals.

Look, at the end of the day these are compounds

that affect cellular processes.

And the more that we understand

how they affect those cellar processes

as we now do for things like acetylcarnitine,

I think the more trust that we can put into them,

or the more to which we might want to avoid them

because of some of the side effects

or contra-indications that those compounds could have.

If you're interested in those other compounds,

I do invite you as I always do to check out examine.com,

but also to do your research on those compounds

by simply putting them into Google

or putting them into PubMed, which would be even better.

And if you are going to go into PubMed,

if you're going to start playing scientist,

which I do encourage you to do,

I would encourage you to not just read abstracts,

but if you can, if the studies are freely available,

I realized not all of them are freely available

to try and read those studies

at least to the extent that you can.

There's a particularly nice study that you might look at

that was published in 2010 in Pain Medicine,

which is Keynan et al K-E-Y-N-A-N,

which looked at the safety and efficacy

of dietary agmatine sulfate

on lumbar disc associated radiculopathy

not laughing at the condition.

It's a painful condition that describes a,

it's a kind of a range of symptoms that relate

to pinching of nerves.

The spinal columns,

I was laughing at my pronunciation of it.

That particular study is quite good.

And the conclusion of that study that they drew was that

there were limited side effects

and that dietary agmatine sulfate is safe

and efficacious for treating and alleviating pain

and improving quality of life

and lumbar-disc associated pain.

However, there were very specific dosage regimens

that were described there and duration of treatment.

And so you should not take anything that I say or that study

to mean that you can just take this stuff willy-nilly

or at any concentration of course, or dose.

You always want to pay attention to what the science says.

That paper fortunately is freely available online.

And we will also provide a link to that study.

For those of you that are interested in SAMe

and its usage for the treatment of various types of pain,

and perhaps other benefits,

a number of companies have stopped making SAMe

instead what they're now focusing on is what they think

is a better or more bioavailable alternative,

which is 5-methyltetrahydrofolate or 5-MTHF.

This molecule is necessary for converting homocysteine

to methionine, which is then converted to SAMe

so rather than taking SAMe directly,

the idea is to take something that's upstream

of SAMe and make more SAMe endogenously available.

This is a different strategy.

I've talked about this strategy before

for increasing other things like growth hormone, et cetera.

There's always this question of whether or not

in trying to increase the amount of a particular molecule

in the body, whether or not taking that specific molecule

was the best thing or working further upstream

as it's referred to working on the precursor

or increasing the levels of the precursor

is the better way to go.

It appears that this 5-MTHF is the strategy

that people are now taking in place of taking SAMe directly.

So in other words, they're taking this

in order to get elevated levels of SAMe.

Now, I'd like to turn our attention

to a completely non drug, non supplement related approach

to dealing with pain.

And it's one that has existed for thousands of years.

And that only recently has the Western scientific community

started to pay serious attention to,

but they have started to pay serious attention to it.

And there is terrific mechanistic science to now explain

how and why acupuncture can work very well

for the treatment of certain forms of pain.

Now, first off, I want to tell you what was told to me

by our director or Chief of the Pain Division

at Stanford School of Medicine, Dr. Sean Mackey,

which was that some people respond very well

to acupuncture and others do not.

And the challenge is identifying who'll respond well

and who won't respond well.

Now, when I say won't respond well,

that doesn't necessarily mean that they responded

in a negative way, that it was bad for them,

but it does appear that a fraction of people

experienced tremendous pain relief from acupuncture

and others experience none at all or very little

to the point where they have to seek out

other forms of treatment.

The science on this is still ongoing.

There was actually an excellent paper published on this

in the Journal of the American Medical Association,

one of the premier medical clinical journals.

And it basically reinforced the idea

that you have responders and non-responders.

A number of laboratories have started to explore

how acupuncture works.

And one of the premier laboratories for this

is Qiufu Ma's lab at Harvard Medical School.

Qiufu has spent many years studying the pain system

and a system that's related to the pain system,

which is the system that controls our sensation of itch.

Just as a brief aside about itch,

itch and pain are often co associated with one another.

I was recently in Texas, and I will tell you,

they have some mean mosquitoes.

They're small, but whatever they're injecting

into your skin.

Well, here I am talking now about my subjective experience

of pain, whatever they injected into my skin

felt to me like the most extreme mosquito bites

I've ever had, not while they were biting me,

not while they were injecting the venom, but boy,

those Texas mosquitoes make me itch.

How do they do it?

Well, their venom creates little packets

of so-called histamine that travel around

those packets are called mast cells,

little packets of histamine that go to that location

and make me and presumably you

want to scratch those mosquito bites.

I scratch mine you scratch yours,

but we both scratch our mosquito bites.

And when we do that, the histamines are released.

That gets red and inflamed and the itch even worse.

The inflammation is actually caused by the histamine.

Well, that experience of inflammation and pain and itch

is what we call a pyrogenic experience.

So we we have pain which is nociception, essentially,

I know that the pain of aficionado

always get a little upset because they say, oh,

there's no such thing as as a pain receptor,

it's no susceptive receptors

and pain is subjective experience.

Yes, I acknowledge all that.

But for fluency, let's just think about pain

as a certain experience and itch as a separate experience,

but they often exist together because those mosquito bites

were what I would call painful, or at least not pleasant.

They didn't just itch, they were also painful nuts

because itch brings with it inflammation

and inflammation often brings with it pain relief,

but it can also bring with it the sensation of pain.

So itch and pain are two separate phenomenon.

It was actually discovered through a really interesting

phenomenon that relates to something

that is actually consumed in supplement form,

which is this tropical legume.

It's actually a bean called Mucuna pruriens.

That's M-U-C-U-N-A that's one word P-R-U-I-E-N-S

Mucuna pruriens is a bean, it's as legume that this bean

is 99% L-DOPA.

It's dopamine or rather it's the precursor to dopamine

and people buy this stuff and take it over the counter

as ways to increase their levels of dopamine.

It does make you feel really dopamine doubt,

meaning it makes you feel a little high and really motivated

and really energetic a lot like other drugs

that will do that.

I don't necessarily recommend taking Mucuna pruriens.

I personally don't like taking it.

Doesn't make me feel good.

I crash really hard when I take it.

But on the outside of this bean is a compound

that makes people itch.

So they remove this when you take it in supplement form.

In fact, it's usually in capsule form,

but the outside of this bean, it's like a hairy bean.

And those little hairs contain a compound,

which was actually used to study and identify

these itchy receptors in the skin.

So we don't have time to go into all the details of itch,

but it's pretty interesting that you have these compounds

out in nature that can make us itch.

Inside them they have dopamine.

I mean, this is really weird,

but plant compounds are really powerful.

So don't let anyone tell you that because something's

from a plant or an earth that it's not powerful.

There are very powerful plant and herb compounds.

Mucuna prurien being one of them with dopamine on the inside

and itchy stuff on the outside.

Now, what does this all have to do with acupuncture?

Well, Qiufu Ma's lab has not just identified

the itch pathway, this pruritus genes as they're called,

which causes itch and the pyrogenic phenomenon

of itch being separate from pain.

His lab has also studied how acupuncture causes relief of,

but also can exacerbate pain.

Now, the form of acupuncture that they explored

was one that's commonly in use called electroacupuncture.

So this isn't just putting little needles

into different parts of the body.

These needles are able to pass an electrical current,

not magically, but because they have

a little wire going back to a device

and you can pass electrical current.

Here's what they found.

This is a study published in the journal neuron

Cell Press journal, excellent journal, very high stringency.

So what Qiufu Ma's lab found was that if electroacupuncture

is provided to the abdomen, to the stomach area,

it creates activation of what are called

the sympathetic ganglia.

These have nothing to do with sympathy

in the emotional sense has to do with the stress response.

Sympa just means together.

So it activated a bunch of neurons along the spinal cord.

And the activation of these neurons evolves

neural adrenaline and something called NPY neuropeptide Y.

The long and short of it is that stimulating the abdomen

with electroacupuncture was either anti-inflammatory

or it could cause inflammation.

It could actually exacerbate inflammation depending

on whether or not it was of low or high intensity.

Now that makes it a very precarious technique.

And this may speak to some of the reason

why some people report relief from acupuncture

and others do not.

However, they went a step further and stimulated other areas

of the body using electroacupuncture.

And what they found is that stimulation of the legs

of the hind limbs, as it's called an animals,

and the legs in humans caused a circuit,

a neural circuit to be activated that goes

from the legs up to an area of the base of the brain

called the DMV not the DMH, which I mentioned earlier,

but the DMV like you go to the DMV,

which is a miserable experience for most people, forgive me,

DMV employees, but let's be honest

most people don't enjoy going to the DMV as patrons,

but we have to so we go.

The DMV and low intensity stimulation,

this electroacupuncture of the hind limbs activated the DMV

and activated the adrenal glands,

which sit at top of your kidneys and cause the release

of what are called catecholamines.

And those were strongly anti-inflammatory.

In other words, electroacupuncture of the legs and feet can,

if done correctly, be anti-inflammatory

and reduce symptoms of pain.

And can we think accelerate wound healing

because activations of these catecholaminergic pathways

can accelerate wound healing as well.

So the takeaway from this is that while there are thousands

of years and millions of subjects involved in explorations

of electroacupuncture and acupuncture,

Western medicine is starting to come into this

and start to explore underlying mechanism.

Now, for those of you that love acupuncture

and are real proponents of it,

it's worked for you, you might say,

well, why does Western medicine even need to come into this?

Why should they even be exploring this?

But we should all be relieved that they are

because what's starting to happen now

is that as the mechanistic basis for this

is starting to come to light,

insurance coverage of things like acupuncture

is starting to emerge as well.

And this is in contrast to other therapies

for which there's a lot of anecdotal evidence,

but very little mechanistic understanding.

One example of that would be laser photo biomodulation

the use of lasers of different types really

to treat pain and to accelerate wound healing.

A lot of people claim that this can really help them.

However, most places, at least in the States,

won't cover this with insurance

or don't perform this in standard clinics.

And the reason is the underlying mechanism isn't known.

I'm not going to get into the argument about whether or not

mechanistic understanding should or should not be required

in order to have insurance coverage of things that work.

That's not what this is about.

And that actually will be a boring discussion

because I'm shouting at a tunnel through you.

And I wouldn't be able to hear you shout back

no matter what your stance on that is,

but just trust me when I say that I am both relieved

and delighted to hear that excellent medical institutions

like Stanford are starting to think about electroacupuncture

and how it can work.

That places like Harvard Medical School are starting

to explore this at a mechanistic level.

And I do believe that there's an open-mindedness

that starting to emerge for instance,

the National Institutes of Health,

not only has an institute for mental health

and cancer research and an eye institute,

but now complementary health, the so-called NCCIH.

National Institutes of Complementary Health

that is exploring things like electroacupuncture,

meditation, various supplements and things of those sort.

I do think that we're entering a new realm in which things

like pain and pain management will be met with more openness

by all physicians, at least that's my hope.

So please take that into consideration right now.

The mechanistic evidence for laser photobiomodulation

is not strong.

One of the major issues or the barriers to that

is that most of the studies that are out there

were actually paid for by companies

that build devices for laser photobiomodulation.

And so we really need independent studies funded

by federal institutions that have no bias

or financial relationship in order to gain trust

in whatever data happen to emerge.

There is a technique that at one time

was considered alternative,

but now has a lot of mechanistic science

to explain how it works, and it does indeed work

for the treatment of chronic and also for acute pain.

And that treatment is hypnosis in particular self-hypnosis.

Now, my colleague at Stanford in fact, my collaborator,

Dr. David Spiegel, our Associate Chair of Psychiatry

has devoted his professional life

to developing hypnosis tools that people can use

to help them sleep better, focus better,

stay motivated, et cetera.

While most people hear hypnosis and they think,

oh, this is stage hypnosis.

People walking around like chickens

are being forced to laugh

or fall asleep on command, et cetera.

This is completely different than all that.

This is self hypnosis and there are now dozens,

if not more quality peer reviewed studies published

in excellent journals done by Dr. Spiegel

and others at other universities.

It really all has to do with how self-hypnosis

can modulate activity of the prefrontal cortex

and related structures like the insula.

The prefrontal cortex is involved in our executive function

as it's called, our planning, our decision making,

but also how we interpret context,

what the meaning of a given sensation is.

And that's extremely powerful.

I just want to remind everybody that the currency

of the brain and body has not changed

in hundreds of thousands of years.

It's always been dopamine, serotonin, glutamate,

GABA, testosterone, estrogen.

What's changed are the contingencies,

the events in the world that drive whether or not

we get an increase or decrease in testosterone or estrogen,

the events in the world that dictate whether or not

we get an increase or a decrease in dopamine.

Believe me, the events that drove those increases

and decreases were very different even a 100 years ago

than they are now.

And as we create new things and societies change, et cetera,

they will continue to exchange information

in the same currency, which is dopamine, serotonin,

and all these other neuromodulators and chemicals.

Hypnosis takes advantage of this

by allowing an individual, you, if you like

to change the way that you interpret particular events

and to actually experience what would be painful

as less painful or not painful.

And that's just the example of pain.

Hypnosis is powerful for other reasons too.

It actually can help rewire neural circuits

so that you don't experience as much pain

so that you can sleep faster, focus faster.

If this is all sounding very fantastical

well, it's supported by data.

The data are that when people do self-hypnosis

even brief self-hypnosis of 10 or 15 minutes,

a few times a week, maybe even returned to that hypnosis

by just using a one minute a day hypnosis,

they can achieve significant and often very impressive

degrees of pain relief in chronic pain

whether or not that chronic pain arises

through things like fibromyalgia or through other sources.

If you want to check this out,

there's a wonderful zero cost resource

that's grounded in this work.

It's the app reveri.com.

So R-E-V-E-R-I.com.

There you can download a zero cost app

for Apple phones or for Android phones.

And there are a variety of different hypnosis scripts.

These are actually self hypnosis scripts,

and you'll actually hear Dr. David Spiegel talking to you.

He can teach you about hypnosis and how it works.

There are links to scientific studies

that web address that I gave you before reveri.com.

You can see the various studies and the various write-ups

related to those studies and how this all works.

And they're simple protocols.

You just click on a tab and you listen to the self-hypnosis

and it will take you into hypnosis.

And several of those hypnosis grips have been shown

clinically to relieve certain patterns of chronic pain.

So it's a powerful tool, and I encourage you not

to write off the non-drug non supplement tools

as less than powerful because indeed many people

experience tremendous relief from them.

And of course, they also can be combined

with drug treatments if that's right for you

or with supplements and things of that sort to treat pain,

if that's right for you.

So again, electroacupuncture now often supported

by insurance, not always, but often.

Great mechanistic data starting to emerge.

Hypnosis, terrific tool.

There's even the self-hypnosis tool that one can access

through the zero cost app Reveri

and lots of great clinical data

and scientific mechanistic data.

There are neuro imaging studies showing

that different brain areas are activated in hypnosis

the so-called default network,

kind of where your brains is kind of idols

and the different circuits that are active in at rest

shift with hypnosis and shift long-term

in ways that positively conserve you.

And then these things like laser photobiomodulation

still more or less in that experimental medical community.

I should say, Western Medical Community, not so certain,

but hopefully there will be data soon,

and hopefully those data will point to mechanisms

that allow the insurance companies

and other sort of medical bodies to support them

if indeed they have a mechanistic basis.

I just want to briefly touch on a common method of pain relief

that speaks to a more general principle

of how things like electroacupuncture,

and also some of these new emerging techniques

of kind of like active tissue release

and this principle that you hear a lot about

in sports medicine now that when you have pain or injury

at one site, that you should provide pressure

above and below that site.

You may have seen this in the Olympics, which is ongoing now

where people will put tape on their body

at certain locations oftentimes.

The logic or what they're saying is that this is designed

to create relief in a joint or in a limb

that's below the tape, not necessarily under the tape,

but above or below.

So for instance, if there's pain in one shoulder,

sometimes we'll put it on the trapezius muscle

or things of that sort.

It turns out that there is a basis for this

because of the way that these different nerves run in

from the skin and from the muscles up into the spinal cord

and into the brainstem providing pressure

on one nerve pathway can often impact another pathway.

And the simplest and most common example of this is one

that we all do instinctually or intuitively

even animals do this.

This is something that in the textbooks is all is called

the Gate Theory of Pain developed by Melzack and Wall

kind of classic theory.

Basically we have receptors in our skin,

the so-called C fibers, that's just a name

for these little wires that come

from a particular class of DRGs that's very thin

that brings about certain kinds

of nasal scepter information.

I want to say pain information,

but then the pain people believe are not their pain people.

Sometimes they're a pain because what they tell me

is they're on pain receptors okay, nociceptors

That information comes in C fibers

and what happens when we injure something

well, provided that we won't damage it worse by touching it,

oftentimes what we will do is we will rub the source of pain

or the location in which we were experiencing pain.

And it turns out that's not an unuseful thing to do.

When we rub our skin or an area,

or we provide pressure nearby it,

we activate the so-called A fibers,

the bigger wires and neurons that innovate,

meaning they jut into that area of skin.

And those A fibers, the ones that respond

to mechanical pressure actually are able to inhibit

those C fibers, the ones that are carrying

that so-called pain information.

So rubbing an area or providing pressure above or below

an injury actually provides real pain relief support

for the location of that injury or that pain

because of the way that these different patterns

or these different types of neurons interact

with one another.

And when I say it inhibits it,

I don't mean that it like shouts at it,

what it does is it releases it's literally kind of

like vomits up a little bit of a neurotransmitter

called GABA.

And GABA is a neurotransmitter that inhibits

it quiets the activity of other neurons.

And so it's acting as kind of an analgesic, if you will,

it's acting as its own form of drug that you make

with your body to quiet the activity of these pain neurons.

So rubbing a wound provided it doesn't damage

the wound worse or providing pressure above or below

typically it's above a particular injury

can have a real effect in relieving some of the pain

of that injury.

And some people have speculated this as through fascia,

or this is through other bodily organs and tissues.

And it might be we're going to do a whole episode on fascia.

It's extremely interesting tissue,

but right now it seems that the main source

of that pain relief is through this A fiber inhibition

of these C fibers so-called Melzack and Wall

Gate Theory of Pain if you'd like to look it up

and learn about that further.

Now, let's talk about a phenomenon

that has long intrigued and perplexed people

for probably thousands of years.

And that's redheads.

You may have heard before that redheads have a higher pain

threshold than other individuals.

And indeed, that is true.

There's now a study that looked at this mechanistically.

There's a gene called the MC1R gene.

And this MC1R gene encodes

for a number of different proteins.

Some of those proteins of course are related

to the production of melanin.

This is why redheads often not always,

but often are very fair skinned.

Sometimes have freckles, not always.

And of course have red hair.

Some people are really intense ginger's

not psychologically or emotionally intense perhaps that too,

but meaning their hair is very, very red.

Others, it's a lighter red.

So of course there's variation here, but this gene,

this MC1R gene is associated with a pathway that relates

to something that I've talked about on this podcast before

during the episode on hunger and feeding and this is POMC.

POMC stands for pro-opiomelanocortin

and POMC is cut up.

It's cleaved into different hormones,

including one that enhances pain perception.

This is melanocyte stimulating hormone.

And another one that blocks pain beta endorphin.

Now, if you listen to the episodes on testosterone

and estrogen and the episodes on hunger and feeding,

some of these molecules will start to ring a bell.

Things like melano stimulating hormone relate

to pigmentation of the skin

relate to sexual arousal, et cetera,

but it turns out that in red heads,

because of the fact that they have this gene,

this MC1R gene, the POMC Pro-opiomelanocortin,

that's cut into different hormones,

melanocyte-stimulating hormones

and another one beta endorphin.

Beta endorphin should cue you to the fact

that this is in the pain pathway.

The endorphins are endogenously made,

meaning made within our body opioids.

They actually make us feel numb

in response to certain kinds of pain.

Now, not completely numb,

but they numb or reduce our perception of pain

because of the ways in which they are released

from certain brain centers.

We'll talk about those brain centers in a moment.

So what's really interesting is that this study showed

that the presence of these hormones is in everybody.

We all have melanocortin 4, we all have beta endorphins.

We all have POMC et cetera,

but red heads make more of these endogenous endorphins.

And that's interesting.

It allows them to buffer against the pain response.

I have a personal anecdote to share with you about

this red head and heightened levels

of pain tolerance phenomenon.

Obviously I'm not a redhead.

I don't dye my hair, but my partner for many years

was a red head and still is a red head.

She had bright red hair and had that since childhood.

Well, we had the fortunate experience

of becoming friends with Wim Hof and family.

They actually came out to visit us and did a series

of seminars in the bay area.

This was in 2016, as I recall.

And my partner, she had never done an ice bath.

She had never done any kind of real cold water exposure

experience before, but as one particular gathering

as is often the case when women's around,

there was an ice bath and a number of people were getting

into this thing.

This was actually before a dinner event.

And I think for most people who have never done an ice bath

getting in for 30 seconds or a minute is tolerable,

but it takes some effort.

It takes some willpower and take some overcoming

that pain barrier 'cause it is a little bit painful.

Not a lot.

Some people can stay in longer three minutes, five minutes

without much discomfort.

What was incredible is that without any desire

to compete with anybody else,

my partner redhead got into the ice bath

and just like sat there for 10 minutes.

In fact, at one point she just kind of turned to me

and said, "I don't really feel pain.

I'm not really in pain."

And Wim loved this.

Wim thought it was great.

He thought it was the most terrific thing in the world.

And he got back in the ice bath

and they became fast friends,

and I think they're probably still fast friends.

So in any event, that's an end of one.

What we call an anecdata example.

Anecdata is not really a term that we should use too much

'cause it's N of one anecdotes are just that.

They're just anecdotes.

But it's been described many times in various clinics

by anesthesiologists, by observation of coaches, et cetera,

that redheads men and women who are redheads

seem to have this higher pain threshold.

And it does seem to be because their body naturally produces

ways to counter the pain response.

They produce their own endogenous opioids.

Now this of course should not be taken to mean that redheads

can tolerate more pain and therefore should be subjected

to more pain, all it means is that their threshold

for pain on average, not all of them,

but on average is shifted higher

than that of other individuals.

And it remains to be determined whether or not

other light skin, light haired individuals

also have a heightened level of pain threshold.

And I should mention because I mentioned the ice bath

that of course pain threshold is something

that can be built up and provide you do that safely

in ways that aren't damaging your tissues

because of course, pain is a signal

that is designed to help you to keep from harming yourself,

but provided that you can do that in a way that's safe

and doesn't damage your tissues,

increasing your pain threshold through the use of things

like ice baths is something that really can be done.

It has a lot to do with these contextual

or top-down modulations of the experience.

You can tell yourself that this is good for me,

or I'm doing this by choice or whatever it is.

You can distract yourself.

There are a huge number of different ways

that one could do that.

One of the more interesting ways

for which there are actually really good scientific data

come from my colleagues, Sean Mackey's Lab.

And that actually looked at how love and in particular,

the experience of obsessive love could actually counter

the pain response, not just in redheads, but in everybody.

So that study I'll just briefly describe

it involved having people come into the laboratory

and experience any one or a number

of different painful stimuli,

but they had selectively recruited subjects

that were in new relationships

for which there was a high degree of infatuation

so much so that the people couldn't stop thinking about

or communicating with that new partner

up to 80% of their waking time, which is a lot.

That constant obsessing about that partner

was correlated with.

It wasn't causal necessarily, but was correlated with

the ability to sustain higher levels of pain

than people who were in more typical non obsessive

forms of love, longstanding relationships,

where there wasn't long obsessive love rather.

And of course in this study,

there were a lot of good control groups.

They included a distractor,

they included people obsessing about other things,

their pet, et cetera.

They included other forms of love and attachment,

but it does seem that certain patterns of thinking

can allow us to buffer ourselves against the pain response.

And that should not be surprising.

Certain forms of thinking are associated with the release

of particular neuromodulators in particular dopamine.

And dopamine, it may seem is kind of the thing

that underlies everything, but it's not.

Dopamine is a molecule that's associated

with novelty expectation, motivation, and reward.

We talked about this at the beginning of the episode,

that it's really the molecule of expectation and motivation

and hope and excitement more than it's associated

with the receival of the reward.

Well, dopamine is coursing throughout the brain

at heightened levels and coursing throughout the body

at heightened levels when we fall in love.

This probably has some adaptive mechanism

that ensure paired bonding between people

or who knows, maybe it ensured not bonding

to multiple people.

Nobody really knows how dopamine functions

in terms of pair bonding,

but it is known that when people fall in love,

new relationships create very high levels of dopamine.

And that's probably the mechanistic basis

by which these people were able to buffer the pain response

by thinking about their partner or this new relationship

that they're in almost obsessively or obsessively.

Now that raises a deeper question

we should always be asking.

Yeah, but how, how?

Well, the dopamine system can have powerful effects

on the inflammation system.

And it doesn't do this through mysterious ways.

It does this by interacting through the brainstem

and some of the neurons that innervate the spleen

and other areas of the body,

that deploy cells to go combat infection,

inflammation, and pain.

And the ways in which dopamine can modulate pain,

and in this case, this particular study

transform our experience of pain.

Maybe even to something that's pleasureful

is not mysterious.

It's really through the activation of brainstem neurons

that communicate with areas of our body,

that deploy things like immune cells.

So for instance, we have neurons in our brain stem

that can be modulated by the release of dopamine

and those neurons in the brainstem control the release

of immune cells from tissues like the spleen

or organs like the spleen.

And those immune cells can then go combat infection.

We've heard before that when we're happy,

we're better able to combat infection, deal with pain,

deal with all sorts of things

that essentially makes us more resilient.

And that's not because dopamine is some magic molecule,

it's because dopamine affects particular circuits

and tells in a very neuro-biological way

in a biochemical way tells those cells and circuits

that conditions are good.

Despite the fact that there's pain in the body

conditions are good.

You're in love or conditions are good.

You want to be in this experience.

Or conditions are good this is for a greater cause

that you're fighting or suffering for some larger purpose.

So all of that has existed largely in the realm

of psychology and even motivational literature

in this kind of thing,

but there's a real mechanistic basis for it.

Dopamine is a molecule that can bind to receptor sites

on these brain areas.

Those brain areas can then modulate the organs and tissues

of the body that can allow us to lean into challenge.

And those challenges can be infection,

it can be physical pain, it can be long bouts of effort

that are required of us.

And I think many people have described the feeling

of being newly in love as a heightened level of energy,

a capacity do anything.

I mean, the whole concept of a muse is one in which

some individual or some thing either imagined or real

enters our life and we can use that as fuel.

And that fuel is chemical fuel

and that chemical fuel is dopamine.

And it really does allow for more resilience

and can even transform the experience of pain

or what would otherwise be pain

into an experience of pleasure.

So, along those lines, let's talk about pleasure.

With all the cells and tissues and machinery related

to pain, you might think that our entire touch system

is designed to allow us to detect pain

and to avoid tissue damage and well,

a good percentage of it is devoted to that.

A good percentage of it is also devoted

to this thing that we call pleasure.

And that should come as no surprise.

Pleasure isn't just there for our pleasure.

It serves adaptive role,

and that adaptive role relates to the fact

that every species has a primary goal

which is to make more of itself

otherwise it would go extinct.

That process of making more of itself sexual reproduction

is closely associated with the sensation

and the perception of pleasure.

And it's no surprise that not only is the highest density

of sensory receptors in and on and around the genitalia,

but the process of reproduction evokes sensations

and molecules and perceptions associated with pleasure.

And the currency of pleasure exists

in multiple chemical systems

but the primary ones are the dopamine system,

which is the anticipation of pleasure

and the work required to achieve the ability

to experience that pleasure, and the serotonin system

which is more closely related to the immediate experience

of that pleasure.

And from dopamine and serotonin stem out other hormones

and molecules, things like oxytocin,

which are associated with pair bonding.

Oxytocin is more closely associated

with the serotonin system biochemically

and at the circuit level meaning the areas of the brain

and body that manufacture a lot of serotonin,

usually not always, but usually contain neurons

that also manufacturer and make use

of the molecule oxytocin.

Those chemicals together create sensations of warmth,

of well being, of safety.

The dopamine molecule is more closely associated

with hormones like testosterone

and other molecules involved with pursuit

and further effort in order to get more of whatever

could potentially cause more release of dopamine.

So this is a very broad strokes,

no pun intended description of the pleasure system.

There are of course, other molecules as well.

One in particular that's very interesting

is something called PEA.

PEA, it stands for Phenethylamine

sometimes also referred to as Phenethylamine

depending on who you are and where you live,

how you pronounce it doesn't really matter.

PEA is a molecule, which is incredibly potent

at augmenting or increasing the activity

of certain cells and neural circuits

that relate to the pleasure system.

PEA has purportedly been thought to be released

in response to ingestion of things like certain forms

of dark chocolate.

Some people take it in supplement form.

It's a bit of a stimulant,

but it also seems to heighten the perception of pleasure

in response to a particular amount of dopamine

and or serotonin.

So for instance, in a kind of a arbitrary experiment

and units type example,

if a given experience evokes a particular

amount of serotonin and dopamine

and gives rise to a subjective experience of pleasure

of say level three out of 10,

the ingestion of PEA prior to that experience can increase

the rating of that experience as more pleasureful.

Maybe a four or a five, or even a six.

And PEA is known to be present in

or I should say it's releases stimulated

by a number of different compounds, such as dark chocolate,

certain things like aspartame and certain people

can actually increase the amount of PEA released.

Some of these glutamate related molecules like aspartame

or things are in the glutamate pathway

can increase PEA release.

And then some people will actually take PEA

in supplement form for its mild stimulant properties

as well as for increasing the perception of,

or the ability to experience pleasure.

It's not a sledgehammer.

It's not like dopamine itself.

People that take things like Mucuna pruriens, L-DOPA

or drugs of abuse, which I certainly don't recommend

things like cocaine or amphetamine

experience tremendous increases in dopamine,

not so much increases in serotonin.

Some people will take serotonin in precursor form

like 5HTP or serotonin itself,

or they'll take the amino acid precursor like tryptophan.

I'm not saying these things as recommendations

for increasingly one sense of pleasure,

I'm describing them because of what they do

generally falls into two categories.

The first category is to raise the foundation,

what we call the tonic level of dopamine and serotonin.

So if levels of serotonin and dopamine are too low,

it becomes almost impossible to experience pleasure.

There's a so-called anhedonia.

This is also described as depression.

Although it needn't be long-term depression.

So certain drugs like antidepressants

like Wellbutrin Bupropion as it's commonly called

or the so-called SSRI,

the serotonin selective re-uptake inhibitors

like Prozac, Zoloft and similar will increase dopamine

and serotonin respectively.

They're not increasing the peaks in those molecules.

What we call the acute release of those molecules,

what they're doing is they're raising the overall levels

of those molecules.

They're raising the sort of foundation

or the tide if you will,

think about it as your mood or your pleasure rather

is like a boat, and if it's on the shore

and it can't get out to sea,

unless that tide is high enough,

that's kind of the way to think about these tonic levels

of dopamine and serotonin.

Now, most of us fortunately,

do not have problems with our baseline or autonic levels

of dopamine and serotonin release.

Things like PEA in that case will cause a slight increase

in that tide and make the ability of certain experiences

to increase dopamine further more available.

What we call this in neurosciences so-called gain control.

I can kind of turn up the volume,

bring us closer to the threshold

to activate certain circuits.

And this is really what we mean

when we say a neuromodulator, okay?

This is why when you are very happy about something,

let's say you're out with your friends.

You're really excited.

Maybe depending on where you live and what's going on

in your area of the world right now,

like I have a niece and she's been locked up in quarantine

for a long time recently because it was deemed safe.

She got to go to summer camp.

I have never seen that kid so happy

to spend with her friends.

She was so excited and it was really amazing

to see how excited she was.

Her baseline levels of dopamine were clearly up

so much so that when she saw her friends,

she literally started squealing.

They were squealing, she was squealing.

Everyone was squealing.

I wasn't squealing.

I would admit it if I was squealing.

I wasn't squealing, but it was such a delight to see

and I'm sure that made my dopamine levels go up,

which was, she was just so excited such that anything

and everything felt like an exciting stimulus.

This is pleasure, right?

And I don't want to write off the experience

from an neuro-biological reductionist standpoint,

quite the opposite.

It's really beautiful to see again this principle

that different experiences and the experience of pleasure

from different things.

Seeing your friends for the first time,

summer camp for a kid,

whatever it might happen to be use the same currency,

dopamine use the same currency serotonin.

And this is a principle that I hope

in listening to this podcast

and even some of it's repetitive features

from one episode to the next.

I'm hoping that those will start to embed in your mind

that the brain and body use these common currencies

for different experiences.

So yes, if your dopamine and serotonin, or I should say

if your dopamine and or serotonin levels are too low,

it will be very hard to achieve pleasure

to experience physical pleasure or emotional pleasure

of any kind.

That's why treatments of the sort

that I described a minute ago might be right for you.

Obviously we can't determine if they're right for you.

It's also why they have side effects.

If you artificially increase these molecules

they're associated with pleasure,

oftentimes you get a lack of motivation

to go seek things like food.

People don't get much interest in food 'cause

why should they if their serotonin levels are already up.

Again, there's a ton of individual variation.

I don't want to say that these antidepressants

are always bad.

Sometimes they've saved lives.

They've saved millions of lives.

Sometimes people have side effects

that make them not the right choice.

So it has to be determined for the individual.

Things like PEA or a more subtle effect.

I should mention PEA supplementation is something

that a number of people use but it's very short-lived.

Because of the half-life of this molecule was very brief,

the effect only lasts about 20 minutes or so.

Things like L-dopa, Mucuna pruriens

lead to longer baseline increases in dopamine.

But remember, any time you raise a baseline,

you reduce the so-called signal to noise.

What it means is if you're riding around

at really high dopamine, at first,