Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

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

and 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 is 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 bout of work, okay?

So this would be like getting a pat on the head

if you’re a dog or 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 of a reward,

and that is the fuel for work.

And every once in a while, 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 counterintuitive.

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.

Our first sponsor is Athletic Greens.

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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 aficionados or those who are curious,

they’re called DRGs, dorsal root ganglia.

A ganglion is just a collection or a 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 and to 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.

Those are extremely long cells.

They can be a meter or more,

depending on how tall you happen to be.

So we have these cells that have wires

that go off in two different directions,

and the wire that’s within our skin

will respond to any number

of different categories of stimuli, okay?

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 fingertip or a feather,

and they respond very robustly.

Others respond to coarse pressure, to 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, okay?

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 hardwired 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 experience is required.

Other things, prior experience is required.

For instance, if you’re somebody

that has a 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.

They 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,

the 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 because you squeezed it like a pizza

and clumped and bunched it all up and put inside the skull.

So 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 courtesies

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, two 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 these 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-point 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 would 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 V5s or V7s, 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 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 that’s 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-3.

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, right?

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, 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 the 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 of 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.

Okay, 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 in 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, it’s 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 stimuli

that can evoke a pain response

and how we would rate that response is much lower at night.

And in particular, in the hours between 2 a.m. and 5 a.m.,

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 redheads,

people who have red 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 and 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

advanced 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 in 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 stub my toe against the corner of the bed,

it absolutely hurts.

But one thing that I’ve noticed

is that I have a 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 have 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 you aficionados.

That simple experiment revealed

that people experienced 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.

Others 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 nocera, 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, a 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, 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

according 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,

you know, I’m, yeah, I’m experiencing some pain in my back.

I’ve got the sciatica thing,

but it, you know, it’s, 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 a 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’s 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 neurobiological 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 it’s been very, very cold,

or has a snowpack going into it.

If it’s 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’s safe,

getting into a cold water

is always going to be easier to do quickly,

and it’s 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 cold 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-degree 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 learn to calm your breathing, et cetera,

lower your autonomic arousal.

Obviously, you don’t want to let your body temperature

go too high because if 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, you know,

up into that range or higher,

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

or get to the 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

or an 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 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,

provided you’re not pregnant, et cetera.

I’ve gone to the dentist, they put you in the chair,

they cover you with a lead blanket,

and then they run behind the screen to protect themselves,

and they beam you 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 experience 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 and 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 mention 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 in 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 and that I have, is very plastic.

It can change.

And so as a consequence,

areas of the map that are 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 describe this.

They feel as if it’s kind of cramped up.

It’s very uncomfortable for them.

Now, an absolutely creative,

and you could even say genius scientist

by the name of Ramachandran,

that’s actually his last name.

His complete name is a little bit more complicated.

So you 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.

He’s done a lot of work on this phantom limb phenomenon.

And Ramachandran 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 it 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,

reduce 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 is 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, Ramachandran 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 Ramachandran 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 innervation

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, right?

It can be because of a cut

to a particular location on the body,

or it can be because, excuse me,

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 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,

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 that 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 a aggregate of 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 or not it’s pain in your body

because 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.

And 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

firm understanding of at least one of the bases

for this whole body pain.

And that’s activation of a particular cell type called glia

and there’s a receptor on these glia,

for those of you that want to know,

called the TOL4 receptor.

And activation of the TOL4 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

relates 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 110th 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 TOL4 receptors on glia.

Okay, so this so-called syndrome

or this thing that previously was called a syndrome,

fibromyalgia, actually has a biological basis.

It was not just in patients’ 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 they’re 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 safe 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 acetyl L-carnitine.

Acetyl L-carnitine, as I mentioned,

is by prescription in most countries in Europe.

In the US, you can buy this over the counter.

There is evidence that acetyl L-carnitine

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, acetyl L-carnitine 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 acetyl L-carnitine

in this context, as well as for diabetic neuropathy.

And what’s interesting about acetyl L-carnitine

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 contexts

to improve peripheral nerve health generally.

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

I’ve also talked about acetyl L-carnitine

on here previously,

because it has robust effects

on things like sperm motility and health,

including the speeds at which sperm swim,

how straight they swim.

Turns out that swimming for sperm is more efficient

if they swim straight,

as opposed to like those kids on the swim team

that are 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 acetyl L-carnitine 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 acetyl L-carnitine 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 acetyl L-carnitine.

You can look those up on PubMed 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.

So M-A-H-D-A-V-I.

The title of the paper is

Effects of L-carnitine Supplementation

on Serum Inflammatory Markers

and Matrix Metalloprotease 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 acetyl L-carnitine.

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 your 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 long term, that’s bad.

And it can secrete anti-inflammatory cytokines like IL-10.

And these matrix metalloproteases, it’s kind of a mouthful,

but these matrix metalloproteases are very interesting.

Anytime you see A-S-E, ACE, that’s generally an enzyme,

which means that these compounds, in this case,

these matrix metalloproteases,

are used to break down certain elements around wounds

and scarring, 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 little ambulances,

like little 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-adenosylmethionine,

which is sometimes called SAMe.

Both of those have been shown to have some impact,

categorized on examiners, notable impact,

on various forms of pain due to osteoarthritis

or due to injury of various kinds

in different 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 dosages.

But it’s also been 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 naproxen

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 worse 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 cellular processes,

as we now do for things like acetyl L-carnitine,

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 contraindications

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 scientists,

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 realize 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 agmentine sulfate

on lumbar disc associated radiculopathy.

I’m not laughing at the condition.

It’s a painful condition that describes,

it’s kind of a range of symptoms

that relate to pinching of nerves in 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 agmentine sulfate is safe and efficacious

for treating and alleviating pain

and improving quality of life

in lumbar disc associated pain.

However, there were very specific dosage regimens,

excuse me, 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

is 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 will 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

experience 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 Chufu Ma’s lab at Harvard Medical School.

Chufu 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, do those Texan 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,

it gets red and inflamed, and they 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 prurogenic experience, okay?

So we have pain, which is nociception, essentially.

I know that the pain aficionados always get a little upset

because they say, oh, there’s no such thing

as a pain receptor, it’s nociceptive 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,

and that’s 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 purines.

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

Mucuna purines is a bean, it’s this 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 dopamined out.

I mean, 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 purines.

I personally don’t like taking it.

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, okay?

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, right?

And those little hairs contain a compound

which was actually used to study

and identify these itch 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 herb

that it’s not powerful.

There are very powerful plant and herb compounds,

mucunipurines 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, Chufu Ma’s lab has not just identified

the itch pathway, there’s pruritogens as they’re called,

which cause itch and the prurigenic 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, excuse me,

published in the journal Neuron, cell press journal,

excellent journal, very high stringency.

So what Chufu 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 involves

noradrenaline 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 in 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 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 atop your kidneys and caused 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 photobiomodulation,

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 would 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’s starting to emerge.

For instance, the National Institutes of Health

not only has a 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 happened 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.

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

or 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.

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 hundred 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 return 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

at 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 scripts

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 neuroimaging studies

showing the different brain areas are activated in hypnosis,

so-called default network,

kind of where your brain kind of idles

and the different circuits that are active at rest

shift with hypnosis and shift long-term

in ways that positively can serve 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 people will 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 called the gait 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 nociceptor information.

I want to say pain information,

but then the pain people,

believe it or not, they’re pain people.

Sometimes they’re a pain because what they tell me

is there aren’t pain receptors, okay, nociceptors.

That information comes in through the 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 innervate,

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.

When I say it inhibits it,

I don’t mean that it like shouts at it.

What it does is it releases,

it 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 is 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 gingers,

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-opio-melanocortin.

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 melanostimulating hormone

relate to pigmentation in the skin,

relate to sexual arousal, et cetera.

But it turns out that in redheads,

because of the fact that they have this gene,

this MC1R gene,

the POMC, pro-opio-melanocortin,

that’s cut into different hormones,

melanocyte-stimulating hormone,

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 redheads 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 redhead

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 redhead

and still is a redhead.

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 there’s one particular gathering,

as is often the case when Wim is 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,

takes some willpower,

and takes some overcoming that pain barrier

because 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, you know, 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 like 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 N of one,

what we call an anecdata example.

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

because it’s N of one anecdotes are just that,

they’re just anecdotes.

But it’s been described many times in various clinics

that were 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 could 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 colleague, 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 ensured pair 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 into something that’s pleasurable,

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 brainstem

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.

It 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 neurobiological 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

and 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 to 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 while 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 an 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 manufacture and make use of the molecule oxytocin.

Those chemicals together create sensations of warmth,

of wellbeing, 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 stands for phenol ethylamine,

sometimes also referred to as phenol ethylamine,

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 its release is 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 that 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 mucunipurines, 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 5-HTP or serotonin itself,

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

I’m not saying these things as recommendations

for increasing the 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 ahedonia.

This is also described as depression,

although it needn’t be long-term depression.

So certain drugs like antidepressants,

like Welbutrin, buprenorphine, as it’s commonly called,

or the so-called SSRIs,

the serotonin selective reuptake inhibitors, excuse me,

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

as 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 our tonic 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 neuroscience is so-called gain control.

It 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, you know,

maybe depending on where you live

and what’s going on in your area of the world right now,

like, you know, 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,

excuse me, spend time 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, okay?

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 a neurobiological 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,

a 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 its 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

that are associated with pleasure,

oftentimes you get a lack of motivation

to go seek things like food.

People don’t get much interest in food

because 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 are 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 is very brief.

The effect only lasts about 20 minutes or so.

Things like L-Dopa, mucunipurines,

lead to longer baseline increases in dopamine.

But remember, anytime 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, everything will start to seem exciting,

like my niece and seeing her friends for the first time,

everything’s exciting.

But then what will happen

is when your dopamine levels return to more normal levels,

it will take a much greater dopamine increase,

a much bigger event, more novel, more exciting,

in order to achieve the sense

that what you’re experiencing is pleasureful.

And this is because of the relationship

between pleasure and pain.

Now, in a future episode,

we are going to go deep into this relationship

between pleasure and pain.

But just briefly, as a precursor to that,

and because it’s relevant to the conversation

that we’ve been having,

you might want to be wary of any experience,

any experience, no matter how it arrives,

chemical, physical, emotional, or some combination,

you might want to be wary of letting your dopamine

go too high, and certainly you want to be wary

of it going too low,

because of the way that these circuits adjust.

Basically, every time that the pleasure system

is kicked in in high gear,

an absolutely spectacular event,

you cannot be more ecstatic.

There is a mirror symmetric activation of the pain system.

And this might seem like an evil curse of biology,

but it’s not.

This is actually a way to protect this whole system

of reward and motivation that I talked about

at the beginning of the episode.

It might sound great to just ingest substances

or engage in behaviors where it’s just dopamine,

dopamine, dopamine, and just constantly be motivated,

but the system will eventually crash.

And so what happens is when you have a big increase

in dopamine, you also will get a big increase

in the circuits that underlie our sense of disappointment

and readjusting the balance.

And with repeated exposure to high levels of dopamine,

not naturally occurring, wonderful events,

but really high chemically induced peaks in dopamine,

high magnitude, chemically induced peaks in dopamine,

what happens is those peaks in dopamine start to go down

and down and down in response to the same,

what ought to be incredible experience.

We start to what’s called habituate or attenuate,

and yet the pain increases in size.

And this has a preservative function in keeping us safe,

believe it or not.

But what I just described is actually the basis of most,

if not all forms of addiction,

something that we will deal with

in a future episode in depth.

So what should you think about all this?

How should you think about pleasure

and how should you think about pain?

What is too much pleasure?

Well, that’s going to differ from person to person,

but to the extent that one can access pleasure repeatedly

over time, ideally without chemical augmentation,

certainly not excessive chemical augmentation,

that means that this pleasure system is tuned up well

and can continue to experience pleasure.

However, if you find yourself engaging

in the same behavior over and over again,

but achieving less and less pleasure from it,

chances are you want to adjust down

how often you engage in that behavior

and or adjust down your expectation of reward

every time you engage in that behavior.

What do I mean by that?

Well, at the beginning of the episode,

I talked about how dopamine will allow us

to get into bouts of hard work.

We will work very hard to pursue a reward.

And that’s really what dopamine does.

And then when the reward comes,

that doesn’t increase our dopamine.

In fact, our dopamine levels go down.

One of the key things that we can all do

to adjust our ability to experience pleasure

is to engage in that intermittent reward schedule.

You can either adjust down the peak in dopamine,

meaning not let yourself ever get too happy,

but that’s no fun, right?

Life is about occasionally achieving

or experiencing ecstasy,

but every once in a while, remove the reward.

And of course, I don’t mean ecstasy the drug.

That’s a separate matter.

The MDMA trials are a separate matter.

Very interesting, I want to be clear.

I meant psychological and physical ecstasy

of the natural sort.

I have immense interest in what’s going on in the MDMA trials

but just for clarity purposes,

that’s a separate topic that we will cover

in an episode, excuse me, very soon.

So how do you adjust this dopamine system?

Well, every once in a while at random,

not in a predictable way, you remove the reward

and that will keep you and your dopamine system

tuned up in the proper ways.

The gain of the dopamine system, as we say,

will be adjusted so that you can continue

to experience dopamine and serotonin

when you actually get the reward.

This can be translated into a huge number

of different domains, but I want to give some examples

because I’m sure that many of you are asking,

wait, what does this actually mean?

Okay, let’s say you’re a student

or this could be a student in academia

or this could be a student of a physical practice.

Every once in a while, when you do something really well,

maybe that’s even just showing up to the practice

rather than pat yourself on the back,

just tell yourself, yeah,

that’s the minimum that’s expected of me.

When everyone’s excited about something that you’re doing,

maybe you’re excited about it,

try and adjust down your excitement a little bit.

I know this might seem counterintuitive,

but you’re preserving the ability

to experience excitement in a variety of contexts.

Let’s say you get a big monetary award.

Well, that’s great, I’m happy for you, and that’s wonderful.

However, you should be a little bit wary

if you care about your dopamine system

and you care about your ability

to get subsequent monetary rewards,

excuse me, awards, rewards, doesn’t matter which,

through effort, if you want to be able

to maintain the ability to exert effort,

well, then you probably wouldn’t want to run out

and immediately buy something with that monetary reward.

In other words, you wouldn’t want to layer on

more dopamine release, okay?

You might, but you might not, you might skip it.

What you’ll find then is that your motivation

is essentially infinite.

This is what I described at the beginning of the episode.

And again, it’s because dopamine is this currency.

It’s like, these days you hear a lot about Bitcoin

and Ethereum and Dogecoin and US dollars and euros

and all this other stuff,

but the currency that you use in your body

doesn’t matter what external currency those are.

In fact, as you watch the value of different currencies

go up, whether or not it’s cryptocurrency

or standard currency, the value is actually reflective

of the dopamine that exists inside of people, right?

So all the excitement about a particular currency,

crypto or otherwise, is really just dopamine.

That’s the currency that we all use.

And there’s no negotiating that.

That’s just the way that we’re built.

Now, to give yet other examples,

let’s say you’re teaching other people how to do something

and they do something exceptionally well.

If you reward them every single time,

and in particular, if you reward them with something

that’s even greater than the experience of what they did,

so let’s say kids win a soccer game and they’re ecstatic,

they’re jumping all over the place, they’re super excited,

and you reward them with an even bigger experience,

a celebration, you are actually inhibiting their ability

to perform the same set of activities

that led them to the win if,

and I really want to underscore if,

you reward them every time.

Of course, we should reward kids and each other

and ourselves for our accomplishments,

but you don’t want to do it every time.

And sure, there will be some disappointment

from suddenly removing the reward that you expected,

but that’s exactly the point.

That’s what keeps these circuits tuned up properly.

Now there’s the other form of pleasure,

which is the more immediate visceral

or sensory experience of pleasure.

This is distinct from goals and goal-directed behavior.

I’m talking about the immediate experience.

This is more of the serotonergic system.

There are other systems involved too,

but this is also the system that draws out

those endogenous opioids from a particular structure.

We have a structure in the back of our brain called PAG,

it’s the periaqueductal gray area.

Very interesting brain area that is associated with pain,

but also with pleasure because under certain conditions,

it deploys endogenous opioids

and gives us a kind of blissed out feeling.

Okay, this is not like the opioids

of the opioid epidemic sort that people take

and unfortunately have led to tremendous amounts

of suffering and abuse.

These are endogenously released opioids.

These are the kind of opioids that come out

from long distance bouts of physical exercise and running.

These are the opioids that are deployed

in response to giving birth

and overcoming the tremendous pain of childbirth.

So PAG is very contextual

and there are a few types of stimuli,

or I should say events in life.

I’m really showing my nerdy side.

There are a few types of stimuli,

I’m talking about experiences,

that evoke endogenous opioid release from PAG.

One is sexual activity.

Sexual activity can increase pain threshold.

And here I am not suggesting

or getting involved in anyone’s particular proclivities

or personal experiences.

You’re welcome to editorialize this however you like.

However, what I’m talking about are animal data

and yes, human data as well,

that show that pain thresholds are increased

anytime PAG is activated

because of the release of these endogenous opioids.

There’s also the immediate experience

of whether or not a particular form of touch

is pleasurable or not.

And there, there’s some very interesting biology

that relates to really how those little wires

from those DRGs innervate our skin.

Work studies, I should say,

done by David Ginty’s lab at Harvard Medical School.

The Ginty lab has spent years

working on the somatosensory system, the touch system,

has identified a particular category of neurons

that innervate the skin.

And then those neurons, of course,

send that information up to the brain too.

And they actually respond to direction of touch.

Now, some of you might be more sensitive to this than others,

but it turns out that certain hairs

like to be deflected one way versus another.

Whether or not you like cats or not,

you can do this experiment.

You can pet a cat in the direction that their fur lies.

So it lies down in a particular direction.

You’ll notice that there’s actually a gene

that dictates that the hairs lie down

in a particular direction.

And if you pet them in a way

that’s cooperating with that direction,

so not pushing the hairs up,

but rather stroking the hairs on the back of the cat,

what you’ll notice is they often like that.

Not all cats, some cats are pretty grouchy,

but if you stroke their hair, they will often purr,

they’ll often push into you.

If you were to stroke their hair in the opposite direction,

pushing the hairs up against the direction

that they want to lie down, cats do not like that.

And it turns out people don’t like that either.

Some people do like to have their hair pushed

in a direction against the direction

in which it wants to lay down,

but there is more typically a response

of feeling like it’s pleasurable for instance,

when someone brushes or combs their hair

in the direction that it wants to lay down.

And that’s because the way in which these neurons

that innervate these hairs sends information

up to the brain, bifurcates actually,

it splits into brain centers that evoke a sense of pleasure

or a sense of not pleasure, it’s not necessarily pain.

So you might find that certain people are very particular.

They like to be touched in a certain way, but not others.

You might be one of those people.

And areas of our skin that have high density of receptors

are very, very sensitive in a real way,

in a real sense of the word to patterns of touch

and whether or not a touch is too firm or too light.

And that will be modulated by overall levels of arousal.

And when I talk about arousal,

what I’m talking about is how alert or how sleepy we are.

It is impossible to experience pain

when we are deep in sleep.

I don’t mean sleeping like of the typical night sort,

I mean of the anesthesia sort.

That’s the purpose of anesthesia,

to bring the brain and body into a deep plane of rest,

very deep in fact.

And it’s very hard, if not impossible to achieve

or experience pleasure

when we are in a very low state of arousal as well.

When we are in heightened states of arousal,

we can achieve pain, we can experience pain

and we can experience pleasure, okay?

And under those heightened states of arousal,

we are more sensitive literally,

the passage of electrical signals

from those locations on the body

that have heightened degrees or higher degrees,

I should say of receptors, use your imagination.

They include the lips, the face, the feet and the genitals

and nearby areas, literally nearby areas.

Under conditions of high arousal, two things happen.

The ability to achieve or experience pleasure

at those locations goes up

and our tolerance and our threshold for pain also goes up.

So the principle here is that as our levels of arousal,

that foundation of arousal goes up or down,

so too goes up and down our ability

to achieve pleasure and pain.

And so these two extremes of being deep within anesthesia

or another extreme is asleep

or in heightened levels of arousal,

our ability to achieve pleasure and pain

are going to scale according to those.

And this is why, and I’m certainly not suggesting this,

but this is why some people will take stimulants

or drugs of abuse that increase arousal

in order to achieve pleasure of other kinds.

The problem is, is that those drugs

and particular things like cocaine and methamphetamine

and amphetamine become their own form of reinforcement,

so much so that the person doesn’t seek out

any other form of excitement or arousal, okay?

So today we weren’t talking about addiction.

We weren’t necessarily talking about motivation,

but we touched on those topics

as sort of a precursor of what’s to come.

We talked about the pathways in the skin and in the brain

and elsewhere in the body

that control our sense of pleasure and pain.

We described a number of different tools

ranging from hypnosis to different supplements

to electroacupuncture and various other tools

that one could use to modulate

your sense of pleasure or pain.

And of course, in thinking about pleasure,

we have to think about the dopamine system

and the serotonin system

and some of the related chemical systems.

I realized that today’s podcast

had a lot of scientific details.

We’ve timestamped everything for you

so that you don’t have to digest it all at once, of course.

I don’t expect that everyone would be able to understand

all these details all at once.

What’s more important really

is to understand the general principles

of how something like pleasure and pain work,

how they interact and the various cells and systems

within the brain and body that allow them to occur

and that modulate or change their ability to occur.

And of course, your subjective experience

of pleasure or pain.

So I do hope that this was on whole

more pleasurable than painful for you.

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and thank you for your interest in science.