How to Control Your Sense of Pain & Pleasure

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science and science-based tools

00:00:04.900 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.540 | and I'm a professor of neurobiology and ophthalmology

00:00:13.060 | at Stanford School of Medicine.

00:00:15.200 | Today, we continue our discussion of the senses,

00:00:18.660 | and the senses we are going to discuss

00:00:20.880 | are pain and pleasure.

00:00:23.500 | Pain and pleasure reflect two opposite ends of a continuum,

00:00:27.380 | a continuum that involves detection of things in our skin,

00:00:32.180 | and the perception, the understanding

00:00:34.740 | of what those events are.

00:00:37.260 | Our skin is our largest sensory organ,

00:00:40.460 | and our largest organ indeed.

00:00:42.620 | It is much larger than any of the other organs in our body,

00:00:46.180 | and it's an odd organ if you think about it.

00:00:48.340 | It has so many functions.

00:00:50.160 | It acts as a barrier between our organs

00:00:52.380 | and the outside world.

00:00:54.180 | It harbors neurons, nerve cells,

00:00:56.580 | that allow us to detect things like light touch,

00:01:00.220 | or temperature, or pressure of various kinds.

00:01:03.860 | And it's an organ that we hang ornaments on.

00:01:06.860 | People put earrings in their ears.

00:01:09.200 | People decorate their skin

00:01:11.060 | with tattoos and inks and other things.

00:01:14.720 | And it's an organ that allows us to experience

00:01:17.900 | either great pain or great pleasure.

00:01:21.720 | So it's a multifaceted organ,

00:01:23.800 | and it's one that our brain needs to make sense of

00:01:26.580 | in a multifaceted way.

00:01:27.980 | So today we're going to discuss all that,

00:01:29.900 | and most importantly, how you can experience more pleasure

00:01:34.520 | and less pain by understanding these pathways.

00:01:37.520 | We will also discuss things you can do,

00:01:40.140 | and if you wish, things you can take

00:01:42.760 | that will allow you to experience more pleasure

00:01:45.700 | and less pain in response

00:01:47.180 | to a variety of different experiences.

00:01:49.980 | Before I go any further,

00:01:51.300 | I want to highlight a particularly exciting area of science

00:01:54.780 | that relates to the skin

00:01:56.280 | and to sensing of pleasure and pain,

00:01:58.580 | but has everything to do with motivation.

00:02:01.980 | Motivation is something that many people struggle with.

00:02:05.520 | Not everybody, but most people experience dips

00:02:10.260 | and peaks in their motivation,

00:02:12.420 | even if they really want something.

00:02:14.340 | How should we think about these changes in motivation?

00:02:16.900 | What do they reflect?

00:02:18.520 | Well, at a very basic level,

00:02:20.120 | they reflect fluctuations,

00:02:22.300 | changes in the levels of a chemical called dopamine.

00:02:26.200 | Most of us have heard of dopamine.

00:02:28.420 | Dopamine is a neuromodulator,

00:02:30.300 | meaning it modulates or changes the way

00:02:32.720 | that neurons, nerve cells work.

00:02:35.400 | Most of us have heard that dopamine

00:02:37.560 | is the molecule of pleasure.

00:02:39.800 | However, that is incorrect.

00:02:41.860 | Dopamine is a molecule of motivation and anticipation.

00:02:46.660 | To illustrate how dopamine works,

00:02:49.740 | I want to highlight some very important work,

00:02:52.180 | largely carried out by the laboratory

00:02:54.400 | of a guy named Wolfram Schultz.

00:02:56.360 | The Schultz Laboratory has done dozens

00:02:59.400 | of excellent experiments on the dopamine system

00:03:03.060 | and have identified something called

00:03:04.720 | reward prediction error.

00:03:07.360 | Although in some sense,

00:03:08.200 | you can think about it as reward prediction variance,

00:03:12.080 | changes in the levels of dopamine,

00:03:13.780 | depending on whether or not you expect a reward

00:03:16.920 | and whether or not you get the reward.

00:03:18.660 | So I'm going to make this very simple.

00:03:20.560 | Dopamine is released into the brain and body

00:03:25.380 | and generally makes us feel activated and motivated

00:03:28.860 | and as if we have energy to pursue a goal.

00:03:32.380 | And it is released into the brain and body

00:03:34.800 | in anticipation of a reward.

00:03:37.380 | Measurements of dopamine have been made

00:03:39.040 | in animals and humans.

00:03:40.560 | What you find is that when we anticipate a reward,

00:03:44.900 | dopamine is released.

00:03:46.640 | We will put in the work to achieve that reward.

00:03:49.300 | That work could be mental work or physical work,

00:03:51.720 | but when the reward arrives,

00:03:54.460 | dopamine levels drop back down to baseline.

00:03:57.320 | That's right.

00:03:58.160 | When we receive a reward,

00:03:59.200 | dopamine levels go back down to baseline.

00:04:02.440 | So the way to envision this,

00:04:03.800 | as you can just imagine a sort of increase in dopamine

00:04:06.780 | as we anticipate something,

00:04:08.000 | we're working towards it,

00:04:09.320 | we're working towards a goal,

00:04:10.640 | we're excited about seeing somebody or meeting somebody

00:04:13.440 | or receiving some reward,

00:04:15.400 | and then the reward comes and dopamine goes down.

00:04:18.520 | Now that's all fine and good,

00:04:20.040 | but there is a way to get much more dopamine

00:04:23.400 | out of that process

00:04:25.000 | and therefore a way to have much more motivation,

00:04:28.120 | energy and focus

00:04:29.280 | because those are the consequences of elevated dopamine.

00:04:33.380 | The way to do that is to not deliver the reward

00:04:38.000 | on an expected schedule.

00:04:40.080 | So experiments have been done

00:04:41.580 | where there's an anticipation of a reward,

00:04:44.280 | there's work and then the reward only arrives every other

00:04:47.940 | or every third bout of work.

00:04:50.640 | So this would be like getting a pat on the head

00:04:53.600 | if you're a dog or perhaps a child or an adult,

00:04:56.920 | or getting a monetary reward only for every third project

00:05:00.920 | or every third race that you win.

00:05:03.520 | Pick any kind of goal, it doesn't matter.

00:05:05.360 | These molecules don't care about what you're pursuing.

00:05:07.600 | They are a common currency of different types of activities.

00:05:11.720 | That's a regular reward schedule

00:05:14.160 | and it will not alter the pattern of dopamine release

00:05:17.000 | that I described before.

00:05:18.660 | However, if the reward arrives intermittently,

00:05:23.420 | almost randomly, so you anticipate a reward as a maybe,

00:05:28.020 | it might come, it might come.

00:05:29.680 | Then you work, work, work, work, work, no reward.

00:05:32.900 | You repeat the work, work, work, work, work, work

00:05:35.240 | and then you get a reward.

00:05:36.260 | So some trials you do, some trials you don't

00:05:38.580 | and it's completely random.

00:05:41.140 | Under those conditions, the amplitude,

00:05:43.640 | the amount of dopamine that's released into your system

00:05:46.560 | and the motivation to continue working hard

00:05:49.880 | or playing whatever kind of game you're playing,

00:05:52.500 | doubles or triples.

00:05:54.180 | And this is the basis of things

00:05:55.480 | like slot machines and gambling.

00:05:56.920 | And this is why so many people will give so much

00:05:59.680 | of their money up to casinos and the casinos always win.

00:06:04.680 | Sometimes people walk away with more money

00:06:07.680 | than they came to the casino with,

00:06:09.400 | but the vast majority of the time,

00:06:11.740 | the house wins, as they say.

00:06:13.560 | And it's because they understand

00:06:15.100 | intermittent reward schedules.

00:06:16.560 | And you can apply this to stay motivated

00:06:19.040 | in your own pursuits.

00:06:21.080 | Rather than thinking about the pleasure of a reward,

00:06:24.480 | understand that dopamine is released

00:06:27.440 | in response to anticipation of a reward.

00:06:30.340 | And that is the fuel for work.

00:06:33.320 | And every once in a while at random, remove the reward.

00:06:37.980 | That's the way to continue to stay motivated,

00:06:40.080 | not to reward every action or every goal.

00:06:43.480 | And this is also true if you're trying to train up children

00:06:47.120 | or train up players on a team,

00:06:49.720 | you should not celebrate every win.

00:06:52.260 | I know that's a little counterintuitive.

00:06:53.880 | We're going to go more into the biology of dopamine

00:06:57.700 | and how it relates to the pleasure system

00:06:59.640 | later on in the podcast.

00:07:01.100 | But for now, understand intermittent reward schedules,

00:07:05.080 | harness the biology of dopamine

00:07:07.180 | in ways that can allow you

00:07:08.800 | essentially infinite motivation over time.

00:07:12.440 | Before I go any further,

00:07:13.560 | I want to acknowledge that this podcast

00:07:15.200 | is separate from my teaching and research roles at Stanford.

00:07:18.040 | It is however, part of my desire and effort

00:07:20.160 | to bring zero cost to consumer information

00:07:22.520 | about science and science-related tools

00:07:24.700 | to the general public.

00:07:26.160 | In keeping with that theme,

00:07:27.300 | I'd like to thank the sponsors of today's podcast.

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00:12:02.300 | So let's talk about pleasure and pain.

00:12:05.480 | I think we all intuitively understand

00:12:07.360 | what pleasure and pain are.

00:12:09.520 | Pleasure generally is a sensation in the body

00:12:12.180 | and in the mind that leads us to pursue more

00:12:16.260 | of whatever is bringing about that sensation.

00:12:19.460 | And pain is also a sensation in the body and in the mind

00:12:24.920 | that in general leads us to want to withdraw

00:12:28.120 | or move away from some activity or interaction.

00:12:31.840 | That's not always the case.

00:12:33.080 | Some people actively seek out pain.

00:12:35.440 | Some people somehow can't seem to engage with

00:12:39.380 | or experience pleasure.

00:12:40.860 | But most people operate on this basis of pleasure and pain.

00:12:45.080 | Scientists would call this a pettative behaviors,

00:12:48.280 | meaning behaviors that lead us to create an appetite

00:12:51.680 | for more of those behaviors and aversive behaviors,

00:12:55.560 | behaviors that make us want to move away from something.

00:12:58.760 | The simplest example of that would be putting your hand

00:13:01.520 | near a hot flame.

00:13:02.840 | At some point, there would be a reflex

00:13:05.160 | or a deep desire to withdraw your hand.

00:13:08.720 | Tasting something delicious in general

00:13:10.680 | makes us want to eat more of that thing.

00:13:13.080 | Interactions with other people that we find delicious

00:13:16.000 | also make us want to interact with those people more.

00:13:18.720 | None of this is complicated or sophisticated.

00:13:21.280 | This is simply to illustrate the fact that pleasure and pain

00:13:25.600 | tend to evoke opposite responses,

00:13:27.680 | opposite behavioral responses

00:13:29.320 | and opposite emotional responses.

00:13:31.440 | So how does that come about?

00:13:33.160 | Well, it really comes about by an interaction

00:13:36.080 | that starts at one end of our body, meaning our skin,

00:13:40.180 | and the other end of the organs of our body,

00:13:42.920 | which is deep within the brain.

00:13:44.640 | So let's consider these two ends of the spectrum

00:13:47.480 | of pleasure and pain and what they contribute

00:13:50.420 | to those experiences of pleasure and pain.

00:13:52.720 | The organ that we call the skin, as I mentioned earlier,

00:13:56.600 | is the largest organ in our body.

00:13:58.880 | And throughout that organ, we have neurons,

00:14:02.160 | little nerve cells.

00:14:03.260 | Now, to be really technical about it,

00:14:05.000 | and the way I'd like you to understand it,

00:14:07.020 | is that the so-called cell body,

00:14:09.220 | meaning the location of a cell in which the DNA

00:14:12.280 | and other goodies, the kind of central factory of the cell,

00:14:15.480 | that actually sits right outside your spinal cord.

00:14:18.320 | So all up and down your spinal cord on either side

00:14:22.140 | are these little blobs of neurons,

00:14:24.440 | little collections of neurons.

00:14:25.940 | They have a name, if you'd like to know,

00:14:27.320 | for you aficionados or those who are curious,

00:14:29.340 | they're called DRGs, dorsal root ganglia.

00:14:33.200 | A ganglion is just a collection or a clump of cells.

00:14:37.160 | And those DRGs are really interesting

00:14:39.620 | because they send one branch that we call an axon,

00:14:43.400 | a little wire, out to our skin,

00:14:46.060 | also to our muscles and to our organs.

00:14:48.060 | But here we're talking about the skin.

00:14:49.500 | They send a wire out to our skin,

00:14:51.160 | and that wire literally reaches up into the skin.

00:14:55.260 | It's actually in our skin.

00:14:57.160 | And they have another wire from that same cell body

00:15:00.320 | that goes in the opposite direction,

00:15:01.560 | which is up to our brain,

00:15:03.520 | and creates connections within our brain

00:15:06.740 | in the so-called brainstem.

00:15:08.480 | What this means is that the neuron in your body

00:15:13.480 | that we call the DRG that sends a wire, an axon,

00:15:17.960 | to sense what's going on in your big toe,

00:15:21.460 | and then sends another axon in the opposite direction

00:15:24.180 | into the base of your brain.

00:15:25.680 | That is the largest cell in your entire body of any kind,

00:15:29.860 | fat cell, muscle cell, nerve cell, et cetera.

00:15:33.040 | Those are extremely long cells.

00:15:34.720 | They can be a meter or more,

00:15:36.220 | depending on how tall you happen to be.

00:15:38.160 | So we have these cells that have wires

00:15:39.980 | that go off in two different directions,

00:15:41.360 | and the wire that's within our skin

00:15:44.040 | will respond to any number of different categories

00:15:48.400 | of stimuli, okay?

00:15:50.000 | These wires are positioned within the skin

00:15:52.980 | to respond to mechanical forces, so maybe light touch.

00:15:57.080 | Some will only send electrical activity

00:16:00.520 | up toward the brain in response to light touch,

00:16:04.440 | meaning if you press on the skin really hard,

00:16:06.600 | they don't respond.

00:16:07.760 | You stroke the skin lightly with your fingertip or a feather,

00:16:10.800 | and they respond very robustly.

00:16:13.600 | Others respond to course pressure, to hard pressure,

00:16:17.080 | but they won't respond to a light feather.

00:16:20.240 | For instance, others respond to temperature.

00:16:23.360 | So they will respond to the presence of heat

00:16:26.280 | or the presence of cold or changes in heat and cold.

00:16:30.000 | And still others respond to other types of stimuli,

00:16:33.140 | like certain chemicals on our skin.

00:16:35.820 | Many of you have probably experienced the sensation

00:16:38.320 | of eating a hot pepper.

00:16:40.140 | Well, I don't recommend doing this,

00:16:41.600 | but were you to take a little slice of jalapeno

00:16:44.160 | or other hot pepper, habanero pepper or something like that,

00:16:47.040 | and rub it on your skin,

00:16:48.480 | you would actually feel something at that location.

00:16:52.140 | And that's because that pepper

00:16:54.120 | doesn't just create a sensation within your mouth,

00:16:56.600 | it will create a similar sensation on your skin.

00:17:00.000 | So these neurons are amazing.

00:17:01.320 | They're collecting information of particular kinds

00:17:04.320 | from the skin throughout the entire body

00:17:06.840 | and sending that information up toward the brain.

00:17:10.100 | And what's really incredible,

00:17:11.960 | I just want you to ponder this for a second.

00:17:14.040 | What's really incredible is that the language

00:17:15.920 | that those neurons use is exactly the same.

00:17:18.820 | The neuron that responds to light touch

00:17:21.300 | sends electrical signals up toward the brain.

00:17:23.760 | The neurons that respond to cold or to heat

00:17:27.220 | or to habanero pepper,

00:17:29.500 | they only respond to the particular thing

00:17:33.080 | that evokes the electrical response.

00:17:36.840 | I should say that they only respond

00:17:38.900 | to the particular stimulus,

00:17:40.780 | the pepper, the cold, the heat, et cetera,

00:17:42.800 | that will evoke an electrical signal.

00:17:45.440 | But the electrical signals are a common language

00:17:48.040 | that all neurons use.

00:17:49.340 | And yet if something cold is presented to your skin

00:17:53.080 | like an ice cube,

00:17:54.440 | even if you don't see that ice cube,

00:17:56.360 | if your eyes are closed or someone comes up behind you

00:17:58.720 | and puts an ice cube against your bare skinned back,

00:18:02.480 | you know that that sensation, that thing is cold.

00:18:05.920 | You don't misperceive it as heat

00:18:08.000 | or as a habanero pepper, okay?

00:18:10.400 | So that's amazing.

00:18:11.340 | What that means is that there must be another element

00:18:14.640 | in the equation of what creates pleasure or pain.

00:18:17.900 | And that element is your brain.

00:18:20.680 | Your brain takes these electrical signals

00:18:22.440 | and interprets them partially based on experience,

00:18:25.740 | but also there are some innate,

00:18:27.620 | meaning some hardwired aspects of pain and pleasure sensing

00:18:31.560 | that require no experience whatsoever.

00:18:33.880 | A child doesn't have to fall down,

00:18:36.340 | but wants to know on that first fall that hurt.

00:18:40.160 | They don't have to touch a flame, but once,

00:18:42.160 | and the very first time they will withdraw their hand

00:18:44.340 | from the flame.

00:18:45.880 | So no prior experience is required.

00:18:48.520 | Other things, prior experience is required.

00:18:51.160 | For instance, if you're somebody that has

00:18:53.060 | a intense aversion to spicy foods,

00:18:56.900 | that's probably because you've tasted spicy foods before.

00:19:00.400 | Likewise, if you really like sweet foods,

00:19:03.020 | it's probably because you've tasted them before.

00:19:05.420 | So you can start to make predictions

00:19:06.720 | based on prior experience,

00:19:07.920 | but the pain and pleasure system

00:19:09.240 | don't need prior experience.

00:19:11.560 | What they need is a brain that can interpret

00:19:13.640 | these electrical signals.

00:19:14.660 | They can take these electrical signals

00:19:16.080 | and somehow create what we call pleasure

00:19:19.080 | and pain out of them.

00:19:21.100 | So what parts of the brain?

00:19:22.720 | Well, mainly it's the so-called somatosensory cortex,

00:19:26.280 | the portion of our neocortex,

00:19:28.680 | which is on the outside of our brain,

00:19:30.040 | the kind of bumpy part, not kind of,

00:19:31.960 | if you have a normally formed brain, it will be bumpy.

00:19:34.880 | If you have a smooth brain, that's not good.

00:19:36.960 | Some animals just have a smooth brain.

00:19:38.700 | Humans have a bumpy brain,

00:19:40.020 | which means it has a very large surface area.

00:19:41.580 | And those bumps are 'cause you squeezed it like a pizza

00:19:44.180 | and bunched it all up and put inside the skull.

00:19:47.220 | So that's good.

00:19:48.060 | That means you have a lot of neurons.

00:19:49.940 | And in your somatosensory cortex,

00:19:52.260 | you have a map of your entire body surface.

00:19:54.640 | That map is called a homunculus.

00:19:57.600 | And if we were to take your cortex and lay it out on a table,

00:20:01.500 | I've actually done this with the cortices

00:20:03.340 | of various animals and humans included.

00:20:07.040 | What you would find is that there's literally a map

00:20:10.040 | of your entire body surface,

00:20:12.500 | but it wouldn't look exactly like you.

00:20:14.960 | This map would be very distorted.

00:20:17.080 | Why would it be distorted?

00:20:19.320 | Well, certain areas of your body

00:20:21.660 | have a much denser innervation as we call it,

00:20:24.940 | or put simply many more of the sensory wires

00:20:28.880 | from these DRGs within your skin.

00:20:31.260 | So this map of you that exists in your brain,

00:20:33.660 | and you do have one of these on each side of your brain.

00:20:36.260 | So you have two of these maps, two homunculi.

00:20:39.620 | That is you.

00:20:40.460 | It's your representation of touch,

00:20:42.340 | including pleasure and pain.

00:20:44.180 | And in that map, your lips are enormous

00:20:48.700 | and your back is very, very small.

00:20:51.720 | And the area around your eyes

00:20:53.400 | and the area representing your face is absolutely enormous.

00:20:57.420 | So you would look like some sort of odd, weird clay doll

00:21:00.420 | from some sort of bizarre late night animation thing.

00:21:03.380 | And just imagine the psychedelic experience

00:21:05.860 | of that character of you,

00:21:08.640 | and that's what it would look like.

00:21:10.460 | But it's not randomly organized.

00:21:12.520 | To the contrary, it's highly organized

00:21:15.200 | in a very particular way,

00:21:17.060 | which is that the areas of your skin

00:21:19.540 | that have the highest density of these sensory receptors

00:21:23.960 | are magnified in your brain.

00:21:26.620 | So it's sort of like having more pixels in a certain part

00:21:30.700 | of a camera than others.

00:21:32.820 | And in doing that, allowing higher resolution,

00:21:35.900 | in this case of touch, not a vision,

00:21:38.460 | but of touch sensation in certain parts of your body.

00:21:42.340 | What are the areas that are magnified?

00:21:44.340 | Well, the lips, the face, the tips of the fingers,

00:21:48.580 | the feet, and the genitals.

00:21:51.060 | And so this map of you has very large lips, face,

00:21:55.420 | tips of fingers, bottoms of feet, and genitals.

00:21:58.420 | And that's because the innervation, the number of wires

00:22:02.660 | that go into those regions of your body

00:22:05.180 | far exceeds the number of wires for sensation of touch

00:22:09.300 | that go to other areas of your body.

00:22:12.400 | You can actually experience this in real time right now

00:22:16.460 | by doing a simple experiment

00:22:17.820 | that we call two-point discrimination.

00:22:20.420 | Two-point discrimination is your ability

00:22:22.980 | to know whether or not two points of pressure

00:22:26.380 | are far apart, near each other,

00:22:29.880 | or you actually could perceive incorrectly

00:22:33.220 | as one point of pressure.

00:22:35.320 | You might want a second person to do this experiment.

00:22:38.580 | Here's how you would do it.

00:22:39.620 | You would close your eyes.

00:22:40.940 | That person would take two fine points.

00:22:43.420 | Don't make them too sharp, please.

00:22:44.780 | So it could be two pencils or pens or the backs of pens.

00:22:47.760 | Two pens I'm holding in my hands.

00:22:49.160 | If you're just listening to this, I'm just holding two pens.

00:22:52.200 | My favorite pens, these Pilot V5s or V7s, which I love.

00:22:56.100 | If you were to close your eyes

00:22:58.160 | and I were to take these two pens

00:23:00.560 | and put their points close together about a centimeter apart

00:23:03.720 | and present them to the top of your hand,

00:23:05.660 | I'm just going to do that now to myself,

00:23:07.380 | you, even though your eyes were closed,

00:23:09.160 | you would be able to perceive

00:23:10.220 | that that was two points of pressure

00:23:12.340 | presented simultaneously to the top of your hand.

00:23:15.260 | However, if I were to do this to the middle of your back,

00:23:18.880 | you would not experience them as two points of pressure.

00:23:21.660 | You would experience them as one single point of pressure.

00:23:25.060 | In other words, your two point discrimination is better,

00:23:27.860 | is higher on areas of your body,

00:23:30.860 | which have many, many more sensory receptors.

00:23:33.700 | You are more sensitive at those locations.

00:23:36.580 | Now this makes perfect sense once you experience it

00:23:39.020 | or you hear about it.

00:23:40.420 | However, most of us don't really appreciate how important

00:23:44.020 | and what a profound influence this change in density

00:23:47.280 | of receptors across our body surface has.

00:23:50.060 | And we can go a step further and describe another feature

00:23:52.600 | of the way that you're built

00:23:53.780 | and the way that you experience pleasure and pain,

00:23:56.020 | which is called the dermatome.

00:23:58.140 | The dermatome is literally the way in which your body surface

00:24:02.740 | is carved up into different territories,

00:24:06.140 | much like a map of the United States

00:24:08.280 | is carved up into different territories

00:24:09.900 | of states and counties, et cetera.

00:24:12.220 | The dermatome is the way in which neurons

00:24:16.020 | connect to different parts of your body.

00:24:18.500 | Now you've actually experienced the dermatome before.

00:24:21.500 | The dermatome is when you have a neuron

00:24:24.120 | that connects to a particular area of the body.

00:24:26.540 | And that neuron doesn't just send one little wire out,

00:24:29.680 | like one little line and go up into the skin

00:24:31.940 | to detect mechanical or thermal or chemical stimuli.

00:24:34.900 | It actually sends many branches out like a tree.

00:24:37.760 | But remember those branches of the tree

00:24:39.860 | come from one single neuron.

00:24:42.420 | Now, occasionally what will happen is you will experience

00:24:45.760 | something like cold or heat or pain or tingling

00:24:50.700 | on a patch of your body.

00:24:52.640 | And occasionally that patch of body

00:24:54.640 | will actually have a very cleanly demarcated boundary,

00:24:58.420 | a very stark boundary with the areas around it.

00:25:02.040 | A good example of this would be the herpes simplex 1 virus,

00:25:05.540 | which if one has this virus,

00:25:07.680 | and I should mention that somewhere between 80 and 90%

00:25:10.660 | of people have this virus.

00:25:12.120 | This is not a sexually transmitted virus.

00:25:14.100 | This is a virus that's transmitted very easily

00:25:16.100 | between people through various forms of contact,

00:25:19.240 | non-sexual contact.

00:25:20.660 | It's present in children, it's present in adults.

00:25:22.840 | And most people get it.

00:25:24.600 | Some get symptoms and some don't.

00:25:26.180 | Some get recurring symptoms, some don't.

00:25:28.080 | We can talk about that at the end if you like.

00:25:30.680 | But this virus lives on what's called

00:25:33.440 | the fifth cranial nerve, also called the trigeminal nerve.

00:25:36.140 | The trigeminal nerve sends branches out to the lips,

00:25:40.540 | to the eyes and to certain portions of the face.

00:25:43.060 | So for those of you listening,

00:25:44.080 | I've just kind of put my right hand across my face

00:25:46.800 | and to sort of simulate the three branches,

00:25:49.240 | the trigeminal aspect of this nerve.

00:25:52.500 | So try three.

00:25:54.160 | Now, when the herpes virus flares up, as they say,

00:25:57.880 | in response to stress or other factors,

00:26:00.920 | the virus inflames that nerve

00:26:03.560 | and people experience tingling and pain on the nerve.

00:26:07.920 | Sometimes they'll get a cold sore or a blister

00:26:10.200 | on their lip or near their mouth.

00:26:11.840 | Sometimes they'll get a collection of those.

00:26:13.620 | And that's because that dermatome is actually inflamed.

00:26:17.840 | Now, other people will experience something like shingles.

00:26:21.720 | It's a fairly common viral infection.

00:26:25.660 | And what they'll notice is they'll get a rash

00:26:27.840 | that has a boundary.

00:26:28.860 | It's like, they'll get a bunch of bumps,

00:26:30.280 | sometimes blisters, and it'll have a sharp boundary.

00:26:33.200 | That boundary exists because the virus exists on the nerve.

00:26:38.000 | And so it actually is boundaried with the neighboring area

00:26:42.200 | of the body that's receiving input from another nerve.

00:26:46.720 | And that one doesn't have the virus living on it.

00:26:49.160 | So anytime you see a rash or a pattern on the body surface,

00:26:53.160 | on the skin, that has a pretty stark boundary,

00:26:55.680 | chances are that's an event that's impacting the dermatome.

00:27:00.320 | I've experienced this before,

00:27:01.720 | not through herpes simplex,

00:27:03.080 | but through the experience of having a lot of blood

00:27:07.600 | sort of aggregating in a kind of a segment

00:27:09.860 | across the front of my face.

00:27:11.040 | It was really bizarre.

00:27:11.880 | I looked in the mirror and I thought,

00:27:12.700 | what is going on here?

00:27:13.540 | I was having an allergic reaction to something I'd eaten.

00:27:16.400 | And that allergic reaction clearly was affecting

00:27:19.480 | one of the nerves and therefore the dermatome.

00:27:21.800 | And what it showed up was,

00:27:23.160 | it was almost like someone had drawn lines on my face

00:27:25.900 | that said, okay, this rash or this reaction rather

00:27:29.100 | can happen here, but not in the region right next to it.

00:27:32.460 | Whenever you see that,

00:27:33.560 | chances are it's a reaction of the nerves of the dermatome.

00:27:37.780 | So you'll start to see these things more and more

00:27:40.060 | when you start to look for them.

00:27:41.700 | You don't always have to have a viral infection

00:27:43.340 | to experience this.

00:27:44.180 | Sometimes you'll just experience tingling

00:27:46.100 | or even a pleasant sensation,

00:27:47.980 | and it will be restricted in kind of a strict boundary

00:27:51.300 | on one location of your body surface and not another,

00:27:54.460 | not corresponding to an organ like, okay, this arm

00:27:58.580 | or just your feet or something like that,

00:28:01.600 | but just a segment.

00:28:02.700 | It's almost like someone outlined a particular area

00:28:05.020 | of your body surface.

00:28:06.180 | That's the dermatome.

00:28:07.500 | Okay, so you've got sensors in the skin

00:28:10.520 | and you've got a brain that's going to interpret

00:28:12.660 | what's going on with those sensors.

00:28:14.980 | In fact, we can take an example of a sudden rash

00:28:18.120 | or inflammation at one location in the dermatome

00:28:20.740 | and we can ask, what would make it hurt?

00:28:24.100 | What would make it worse?

00:28:25.920 | What would make it go away?

00:28:27.940 | And believe it or not, your subjective interpretation

00:28:31.180 | of what's happening has a profound influence

00:28:34.660 | on your experience of pleasure or pain.

00:28:38.020 | There are several things that can impact these experiences,

00:28:41.140 | but the main categories are expectation.

00:28:44.820 | So sort of whether or not you thought or could expect

00:28:47.860 | that this thing was going to happen, right?

00:28:50.600 | If someone tells you this is going to hurt,

00:28:52.500 | I'm going to give you an injection right here.

00:28:54.220 | It might hurt for a second.

00:28:55.540 | That's very different and your experience of that pain

00:28:57.500 | will be very different than if it happened suddenly

00:28:59.440 | out of the blue.

00:29:00.900 | There's also anxiety, how anxious or how high

00:29:03.740 | or low your level of arousal, autonomic arousal.

00:29:07.260 | That's going to impact your experience of pleasure or pain.

00:29:11.540 | How well you slept and where you are

00:29:14.820 | in the so-called circadian or 24-hour cycle.

00:29:17.520 | Our ability to tolerate pain changes dramatically

00:29:22.360 | across the 24-hour cycle.

00:29:24.140 | And as you can imagine, it's during the daylight

00:29:26.420 | waking hours that we are better able to tolerate.

00:29:29.740 | We are more resilient to pain

00:29:32.000 | and we are better able to experience pleasure.

00:29:35.940 | At night, our threshold for pain is much lower.

00:29:39.940 | In other words, the amount of mechanical or chemical

00:29:43.960 | or thermal, meaning temperature stimulated

00:29:45.940 | that can evoke a pain response

00:29:47.380 | and how we would rate that response is much lower at night.

00:29:52.380 | And in particular, in the hours between 2 a.m. and 5 a.m.

00:29:57.340 | if you're on a kind of standard circadian schedule.

00:30:00.100 | And then the last one is our genes.

00:30:02.800 | Pain threshold and how long a pain response lasts

00:30:07.160 | is in part dictated by our genes.

00:30:09.460 | And later I'm going to discuss this myth

00:30:12.500 | or whether or not it's really a myth

00:30:15.160 | as to whether or not certain people in particular redheads,

00:30:18.280 | people who have red pigmented hair and fair skin,

00:30:22.900 | whether or not their pain thresholds differ.

00:30:24.940 | And to just give you a little sneak peek into that,

00:30:27.460 | indeed they do and it's because of a genetic difference

00:30:30.580 | in a particular gene and a particular pattern of receptors

00:30:34.120 | in the skin that are related

00:30:36.300 | to the pigmentation of hair and skin.

00:30:40.100 | So we have expectation, anxiety, how well we've slept,

00:30:43.400 | where we are in the so-called 24 hour circadian time

00:30:47.260 | and our genes.

00:30:48.840 | So let's talk about expectation and anxiety

00:30:52.620 | because those two factors can powerfully modulate

00:30:55.860 | our experience of both pleasure and pain

00:30:58.160 | in ways that will allow us to dial up pleasure if we like

00:31:03.160 | and to dial down pain if indeed that's what we want to do.

00:31:07.300 | So let's talk about expectation and anxiety

00:31:09.820 | because those two things are somewhat tethered.

00:31:12.180 | There are now a number of solid experiments

00:31:15.420 | both in animal models and in humans that point to the fact

00:31:19.700 | that if we know a painful stimulus is coming,

00:31:23.500 | that we can better prepare for it mentally

00:31:26.440 | and therefore buffer or reduce the pain response.

00:31:30.420 | However, the timing in which that anticipation occurs

00:31:35.120 | is vital for this to happen.

00:31:37.580 | And if that timing isn't quite right,

00:31:40.000 | it actually can make the experience of pain far worse.

00:31:43.580 | So here I'm summarizing a large amount of literature,

00:31:46.740 | but essentially if subjects are warned

00:31:49.460 | that a painful stimulus is coming,

00:31:51.800 | their subjective experience of that pain is vastly reduced.

00:31:56.800 | However, if they are warned just two seconds

00:32:01.200 | before that pain arrives, it does not help.

00:32:04.480 | It actually makes it worse.

00:32:06.100 | And the reason is they can't do anything mentally

00:32:08.280 | to prepare for it in that brief two second window.

00:32:11.240 | Similarly, if they are warned about pain that's coming

00:32:15.860 | two minutes before a painful stimulus is coming,

00:32:18.640 | electric shock or a poke or cold stimulus

00:32:21.500 | or heat stimulus that's pretty extreme,

00:32:23.740 | that also makes it worse because their expectation ramps up

00:32:28.660 | the autonomic arousal, the level of alertness

00:32:31.820 | is all funneled toward that negative experience

00:32:35.180 | that's coming.

00:32:36.640 | So how soon before a painful stimulus

00:32:40.640 | should we know about it if the goal

00:32:42.940 | is to reduce our level of pain?

00:32:45.900 | And the answer is somewhere between 20 seconds

00:32:49.660 | and 40 seconds is about right.

00:32:52.040 | Now I'm averaging across a number of different studies,

00:32:54.660 | but if you have about 20 seconds or 40 seconds

00:32:58.700 | advance warning that something bad is coming,

00:33:01.100 | you can prepare yourself for that.

00:33:03.220 | But the preparation itself and the arousal

00:33:05.580 | that comes with it, the kind of leaning in,

00:33:07.040 | okay, I'm either going to relax myself

00:33:09.440 | or I'm going to really kind of dig my heels in

00:33:11.780 | and kind of meet the pain head on,

00:33:13.720 | that seems to be the optimal window.

00:33:16.620 | This can come in useful in a variety of contexts,

00:33:19.360 | but I think it's important because what it illustrates

00:33:23.320 | is that it absolutely cannot be just the pattern of signals

00:33:27.420 | that are arriving from the skin, from these DRGs,

00:33:31.560 | these neurons that connect to skin

00:33:33.520 | that dictates our experience of pain or pleasure.

00:33:36.840 | There has to be a subjective interpretation component.

00:33:40.440 | And indeed that's the case.

00:33:41.980 | So let's talk about the range of pain experiences.

00:33:46.300 | And from that, we will understand better

00:33:48.120 | what the range of pleasure experiences are

00:33:50.620 | that different people have,

00:33:52.020 | because we are all different in terms of our pain threshold.

00:33:55.060 | First of all, what is pain threshold?

00:33:57.180 | Pain threshold has two dimensions.

00:33:59.360 | The first dimension is the amount of mechanical

00:34:03.560 | or chemical or thermal stimulation that it takes

00:34:06.500 | for you or me or somebody else to say,

00:34:09.180 | I can't take that anymore, I'm done.

00:34:11.580 | But there's another element as well,

00:34:13.160 | which is how long the pain persists.

00:34:16.100 | I'll just describe myself, for example,

00:34:18.340 | I don't consider myself somebody

00:34:20.120 | who has a particularly high pain threshold.

00:34:22.500 | I don't think it's particularly low either,

00:34:24.200 | but I wouldn't consider myself somebody

00:34:25.620 | that has a particularly high pain threshold.

00:34:28.260 | When I stub my toe against the corner of the bed,

00:34:30.940 | it absolutely hurts.

00:34:32.820 | But one thing that I've noticed

00:34:34.000 | is that I have very sharp inflections,

00:34:36.020 | very high inflections in my perception of pain,

00:34:39.620 | and then they go away quickly.

00:34:41.420 | I don't know if that's adaptive or not, it's probably not.

00:34:44.140 | But my experience of pain is very intense, but very brief.

00:34:48.380 | Other people experience pain

00:34:50.260 | in a much kind of slower rising, but longer lasting manner.

00:34:54.660 | And to just really point out how varied we all are

00:34:57.700 | in terms of our experience of pain,

00:34:59.660 | let's look to an experiment.

00:35:01.860 | There have been experiments done

00:35:03.280 | at Stanford School of Medicine and elsewhere,

00:35:06.180 | which involved having subjects put their hand

00:35:08.460 | into a very cold vat of water

00:35:10.860 | and measuring the amount of time

00:35:12.420 | that they kept their hand in that water.

00:35:14.300 | And then they would tell the experimenter, very quietly,

00:35:17.940 | how painful that particular stimulus was

00:35:20.940 | on a scale of one to 10,

00:35:22.300 | so-called Likert scale for you aficionados.

00:35:24.800 | That simple experiment revealed

00:35:28.340 | that people experience the same thermal,

00:35:32.420 | in this case cold, stimulus, vastly different.

00:35:36.420 | Some people would rate it as a 10 out of 10, extreme pain.

00:35:40.260 | Other people would rate it as barely painful at all,

00:35:42.980 | like a one.

00:35:43.860 | Other people, a three.

00:35:44.980 | Other people, a five, et cetera.

00:35:47.340 | Now what's interesting is that the same thing is true

00:35:50.280 | for experience of a hot painful stimulus,

00:35:53.540 | 120 degree hot plate where you have to put your hand on it.

00:35:56.860 | And then at some point you remove your hand.

00:35:58.740 | Some people are able to keep their hand

00:36:00.140 | on there the whole time.

00:36:01.700 | But people rate that experience as very painful,

00:36:05.480 | a little bit painful, or moderately painful,

00:36:07.780 | depending on who they are.

00:36:09.560 | Now that's interesting.

00:36:11.740 | Probably not that surprising, however.

00:36:14.360 | But what is very interesting is that

00:36:16.100 | when the same experiment was done on medical doctors

00:36:19.680 | or medical doctors in training,

00:36:21.640 | they too, of course, experienced pain

00:36:24.520 | through a range of subjective experiences.

00:36:27.200 | Some of them, just like any other person off the street,

00:36:30.940 | said a particular stimulus of a particular temperature

00:36:33.760 | was very painful.

00:36:34.760 | Others said it wasn't painful at all.

00:36:36.040 | And some said it was moderately painful.

00:36:38.440 | And that turns out to be vitally important

00:36:40.600 | for the treatment of pain.

00:36:43.100 | Because pain is not an event in the skin.

00:36:45.820 | Pain is a subjective emotional experience.

00:36:49.200 | You may have heard that we have a particular category

00:36:52.240 | of these DRGs that innervate the skin,

00:36:54.400 | which are called nociceptors.

00:36:56.360 | Nociceptor comes from the word nocera, I believe it is,

00:37:01.040 | which means to harm.

00:37:02.640 | However, nociceptors don't carry information about pain.

00:37:06.120 | They carry information about particular types of stimuli

00:37:09.000 | impacting the skin.

00:37:10.520 | And then the brain assigns a value, a valence to it,

00:37:14.120 | a label, and says that's painful.

00:37:16.620 | And where people draw the line

00:37:18.040 | between not painful and painful varies.

00:37:20.400 | Now, because physicians are people

00:37:23.200 | and because physicians treat pain,

00:37:25.600 | what we know from a lot of data now

00:37:28.720 | is that if someone comes into the clinic

00:37:30.940 | and says they're experiencing chronic pain

00:37:32.960 | or whole body pain or acute pain after an injury

00:37:35.560 | or one location, it doesn't really matter what the cause is,

00:37:38.280 | or even if there's a cause at all,

00:37:40.160 | how the doctor reacts to that report of the patient's pain

00:37:46.560 | will dictate in many cases the course of treatment.

00:37:49.480 | And of course, doctors, their goal is to treat the patient

00:37:52.600 | according to the patient's needs, not their own.

00:37:54.720 | And that's what good doctors do.

00:37:56.980 | However, it's been found,

00:37:59.120 | and I think now there is work being done

00:38:01.080 | to try and change this,

00:38:03.280 | but if a doctor has a very high threshold for pain,

00:38:07.540 | their interpretation of somebody else's report of pain

00:38:10.240 | is going to be different.

00:38:11.260 | They might not discount the patient, right?

00:38:13.640 | This doesn't necessarily mean that they think,

00:38:15.080 | oh, this person, you know, their pain is irrelevant.

00:38:17.720 | Probably not.

00:38:18.840 | In fact, from having a high threshold for pain,

00:38:21.540 | if someone comes in and says, I'm in extreme pain,

00:38:24.360 | that doctor probably thinks, wow,

00:38:26.160 | this has to be really, really extreme,

00:38:28.200 | but they can be talking about two different experiences.

00:38:31.780 | Similarly, if a physician has a very low threshold for pain

00:38:35.400 | and someone comes in and says,

00:38:37.620 | you know, I'm, yeah, I'm experiencing some pain in my back.

00:38:41.180 | I've got the sciatica thing, but it, you know, it's, yeah,

00:38:43.420 | it's a little bit uncomfortable.

00:38:44.820 | It's like a, I don't know, like a four out of 10.

00:38:47.540 | Well, that physician might interpret that four out of 10

00:38:50.660 | as a pretty extreme sense of pain

00:38:54.040 | or a pretty extreme experience of pain.

00:38:56.180 | And so you can start to see

00:38:57.440 | how the subjective nature of pain

00:38:59.700 | can start to have real impact on the treatment of pain

00:39:02.740 | because treatment of pain is carried out by physicians.

00:39:05.720 | In fact, there is no objective measure of pain.

00:39:09.920 | We can ask how long somebody can keep their hand

00:39:11.780 | on a hot plate or in a cold bath.

00:39:13.800 | You can do various experiments.

00:39:15.600 | They even have some extreme experiments

00:39:17.440 | where they'll shave a portion of the leg

00:39:20.160 | and they'll put on a very painful chemical compound

00:39:23.780 | and see how long people can tolerate that.

00:39:25.480 | These are very uncomfortable experiments as you can imagine.

00:39:28.420 | But in general, we don't have a way of measuring

00:39:31.100 | somebody else's subjective experience of pain.

00:39:34.040 | There's no blood pressure measure.

00:39:35.760 | There's no heart rate beats per minute measure of pain.

00:39:39.020 | So one of the great efforts of neuroscience and of medicine

00:39:42.400 | is to try and come up with more objective measures of pain.

00:39:46.000 | Similarly, pleasure is something that we all talk about.

00:39:49.220 | Ooh, that feels so good, or I love that,

00:39:51.260 | or more of that, please, or less of that.

00:39:54.020 | But we have no way of gauging

00:39:56.360 | what other people are experiencing

00:39:57.820 | except what they report through language.

00:40:00.900 | And so this is really just to illustrate

00:40:02.980 | that this whole thing around pain isn't a black box.

00:40:05.660 | We do have an understanding of the elements.

00:40:07.860 | There are elements in the skin.

00:40:08.700 | There's elements of the brain.

00:40:09.840 | There's expectation, anxiety, sleep, and genes,

00:40:12.540 | but that it is very complicated.

00:40:15.400 | And yet there are certain principles

00:40:17.260 | that fall out of that complicated picture

00:40:19.720 | that can allow us to better understand and navigate

00:40:22.460 | this axis that we call the pleasure pain axis.

00:40:25.520 | So rather than focus on just the subjective nature of pain,

00:40:28.800 | let's talk about the absolute qualities of pain

00:40:32.240 | and the absolute qualities of pleasure

00:40:35.080 | so that we can learn how to navigate those two experiences

00:40:38.640 | in ways that serve us each better.

00:40:41.000 | First of all, I want to talk about heat and cold.

00:40:44.760 | We do indeed have sensors in our skin

00:40:46.480 | that respond to heat and cold.

00:40:48.480 | And for any of you that have entered a cold shower

00:40:52.040 | or a cold body of water of any kind or ice bath, et cetera,

00:40:56.920 | you will realize that getting into cold

00:41:00.180 | is much harder if you do it slowly.

00:41:03.200 | Now, despite that, people tend to do it very slowly.

00:41:06.900 | I have noticed an enormous variation

00:41:09.320 | with which people can embrace the experience of cold.

00:41:13.400 | I noticed it because I do some work with athletes

00:41:16.400 | and I do some work with military

00:41:17.600 | and I do some work with the general public.

00:41:19.480 | And one of the best tests of how somebody can handle pain

00:41:23.920 | is to ask them to just get into an ice bath.

00:41:27.180 | It's not a very sophisticated experience,

00:41:28.960 | but it really gets into the core of the kind of circuitry

00:41:31.280 | that we're talking about, both in the skin and in the brain.

00:41:35.200 | Some people, regardless of sex, regardless of age,

00:41:39.820 | and regardless of physical ability,

00:41:42.860 | can just get into the cold.

00:41:44.740 | They're somehow able to do it.

00:41:46.800 | Now, I don't know what their experience of the cold is

00:41:48.800 | and neither do you, you only know your experience,

00:41:51.520 | but they're able to do that.

00:41:53.360 | Some do it quickly, some do it slowly.

00:41:55.960 | Others find the experience of cold to be so aversive

00:41:59.560 | that they somehow cannot get themselves in.

00:42:01.760 | They start quaking, they start complaining,

00:42:04.460 | and many of them just simply get out.

00:42:06.820 | They can't do it.

00:42:07.660 | Some don't even get in past their knees.

00:42:09.840 | This isn't necessarily about pain threshold,

00:42:12.040 | but it's related to that.

00:42:13.500 | I think it can be helpful to everyone to know

00:42:17.040 | that even though it feels better at a mental level

00:42:20.400 | to get into the cold slowly and people ask,

00:42:23.240 | oh, I just want to get in slowly, I want to take my time,

00:42:26.640 | it is actually much worse

00:42:27.920 | from a neurobiological perspective.

00:42:30.280 | The neurons that sense cold respond

00:42:32.840 | to what are called relative drops in temperature.

00:42:36.260 | So it's not about the absolute temperature of the water.

00:42:39.780 | It's about the relative change in temperature.

00:42:43.480 | So as you move from a particular temperature,

00:42:46.240 | whether or not it's in the air next to an ice bath

00:42:48.320 | or cold shower, or from a body of water that's warm

00:42:51.320 | to a body of water that's colder,

00:42:53.120 | or sometimes in the ocean, you'll notice it's warm.

00:42:55.140 | And then as you swim out further,

00:42:56.640 | you'll get into a pocket of water where it's much colder.

00:42:59.300 | That's when the cold receptors in your skin start firing

00:43:02.320 | and sending signals up to your brain.

00:43:04.760 | Therefore, you can bypass these signals

00:43:08.640 | going up to the brain with each relative change,

00:43:11.200 | one degree change, two degrees change, et cetera,

00:43:14.580 | by simply getting in all at once.

00:43:17.080 | In fact, it is true.

00:43:18.200 | And maybe you've been told this before,

00:43:19.900 | and it is true that if you get into cold water

00:43:22.480 | up to your neck, it's actually much more comfortable

00:43:25.320 | than if you're halfway in and halfway out.

00:43:27.360 | And that's because of the difference in the signals

00:43:29.760 | that are being sent from the cold receptors

00:43:31.920 | on your upper torso,

00:43:32.880 | which is out of the water in your lower torso.

00:43:34.960 | Now, I wouldn't want anyone to take this to mean

00:43:37.580 | that they should just jump into an unknown body of water.

00:43:39.800 | There are all sorts of factors like currents.

00:43:41.900 | And if it's very, very cold, yes, indeed,

00:43:44.280 | you can stop the heart.

00:43:45.260 | People can have heart attacks

00:43:46.440 | from getting into extremely cold water,

00:43:48.520 | like a melted mountain stream that's been frozen all winter

00:43:53.520 | or has been very, very cold or has a snowpack going into it.

00:43:57.460 | If it's very cold, you can indeed have a heart attack.

00:43:59.580 | So please be smart about how cold

00:44:02.040 | and what bodies of cold water

00:44:03.920 | you happen to put yourself into.

00:44:05.600 | But it is absolutely true that provided it's safe,

00:44:08.120 | getting into a cold water is always going to be easier

00:44:11.180 | to do quickly and is going to be easier

00:44:13.360 | to do up to your neck.

00:44:15.020 | In fact, you actually want to get your shoulders submerged.

00:44:17.960 | There are a number of other things you can do.

00:44:19.660 | If you really want, and it's safe to do,

00:44:21.360 | you can put your face under

00:44:22.800 | and activate the so-called dive reflex,

00:44:24.780 | which also makes the tolerance of cold easier,

00:44:27.960 | believe it or not.

00:44:28.960 | So it's very counterintuitive.

00:44:30.160 | It's like getting into cold water faster

00:44:32.280 | and more completely, you will experience

00:44:34.400 | as less uncomfortable, less cold.

00:44:36.680 | And indeed that's the case.

00:44:38.320 | And that's because these cold receptors

00:44:40.580 | are measuring every relative drop in temperature.

00:44:43.820 | So every single one is graded, as we say in biology,

00:44:47.340 | it's not absolute.

00:44:48.760 | As an additional point,

00:44:51.220 | if you're sitting in a body of cold water

00:44:53.060 | and it's not circulating,

00:44:54.340 | you'll notice that you start to warm up a little bit,

00:44:57.060 | or even if you feel like you're freezing cold,

00:44:59.460 | if you move and that water around you moves, of course,

00:45:02.820 | then you'll notice it's got even colder.

00:45:04.880 | And that's because there's a thermal layer.

00:45:06.460 | You're actually heating up the water

00:45:08.220 | that surrounds your body like a halo

00:45:10.780 | around every aspect of your body,

00:45:12.840 | a sort of silhouette of you of heat

00:45:14.740 | where you're heating that water.

00:45:16.060 | When you move, you disrupt that thermal layer.

00:45:19.780 | Now, heat is the opposite.

00:45:22.060 | Heat and the heat receptors in your skin

00:45:24.260 | respond to absolute changes in temperature.

00:45:26.820 | And this is probably because our body and our brain

00:45:29.940 | can tolerate drops in temperature much better

00:45:32.620 | than it can tolerate increases in temperature safely.

00:45:36.540 | So when you move from say a standard outdoor environment,

00:45:40.220 | I mean, here in the States we measure

00:45:41.420 | in terms of Fahrenheit,

00:45:42.660 | so maybe it's a 75 or an 80 degree or even 90 degree day,

00:45:46.300 | and you get into a 100 degree sauna,

00:45:48.740 | or if you're in a cool air conditioned building

00:45:50.660 | and you go outside and it's very warm outside,

00:45:53.300 | you sort of feel like the heat hits you all at once.

00:45:55.860 | Boom, hits you all at once,

00:45:57.380 | kind of like a slap in the face.

00:45:59.700 | But then it will just stay at that level.

00:46:01.620 | Your body will acclimate to that particular temperature.

00:46:05.460 | However, if that temperature is very, very high,

00:46:08.340 | you'll notice that your experience of that heat

00:46:11.100 | and your experience of kind of pain and discomfort

00:46:13.600 | and your desire to get out of that heat will tend to persist.

00:46:17.220 | You don't really adapt in the same way.

00:46:19.620 | And certain people who are really good at handling

00:46:21.700 | very hot sauna get better at this.

00:46:23.580 | You learn to calm your breathing, et cetera,

00:46:26.100 | lower your autonomic arousal.

00:46:28.180 | Obviously you don't want to let your body temperature

00:46:29.900 | go too high because if neurons cook, they die.

00:46:32.620 | If neurons die, they don't come back and that's bad.

00:46:35.660 | Many people unfortunately harm themselves with hyperthermia.

00:46:39.340 | Everyone has a different threshold for this,

00:46:40.860 | but in general,

00:46:42.580 | you don't want your body temperature to go up too high.

00:46:44.620 | That's why a fever of like 103 starts to become worrisome.

00:46:47.460 | 104, you really get concerned if it goes, you know,

00:46:50.940 | up into that range or higher,

00:46:52.460 | that's when you need to really cool down the body

00:46:54.620 | or get to the hospital so they can cool you down.

00:46:57.020 | Heat is measured in absolute terms by the neurons.

00:47:02.400 | So gradually moving into heat makes sense

00:47:05.620 | and finding that threshold,

00:47:06.860 | which is safe and comfortable for you,

00:47:09.000 | or if it's uncomfortable at least resides

00:47:11.300 | within that realm of safety.

00:47:13.680 | So that's heat and cold.

00:47:14.980 | And those are sort of non-negotiables.

00:47:17.220 | You can try and lower your level of arousal.

00:47:19.620 | In fact, many people who will get into a cold shower

00:47:22.020 | and ice bath, I think the recommendation that I always give

00:47:24.920 | is that you have two possible approaches to that.

00:47:27.900 | You can either try and relax yourself,

00:47:29.580 | kind of just stay calm within the cold,

00:47:32.560 | or you can lean into it.

00:47:33.760 | You can actually take mental steps

00:47:37.800 | to generate more adrenaline

00:47:39.720 | to kind of meet the demands of that cold.

00:47:42.920 | And at some point we'll do a whole episode

00:47:44.640 | on how to use cold and heat to certain advantages.

00:47:47.760 | We've done a little bit of this in past episodes,

00:47:50.560 | using the cold to supercharge human performance

00:47:53.020 | and things of that sort.

00:47:54.240 | But in general, cold is measured in relative terms

00:47:58.040 | and therefore getting in all at once is a good idea

00:48:00.760 | provided you can do it safely.

00:48:02.100 | And heat is measured in absolute levels

00:48:04.760 | by your brain and body.

00:48:05.660 | And therefore you want to actually move into it gradually.

00:48:08.100 | So it's the kind of the inverse of what you might think.

00:48:11.360 | One of the most important things to understand

00:48:13.660 | about the experience of pain

00:48:15.100 | and to really illustrate just how subjective pain really is

00:48:19.640 | is that our experience of pain

00:48:22.060 | and the degree of damage to our body

00:48:24.520 | are not always correlated.

00:48:25.960 | And in fact, sometimes can be in opposite directions.

00:48:29.360 | A good example of this would be x-rays.

00:48:31.780 | We all occasionally get x-rays,

00:48:33.360 | at least in the US we get x-rays

00:48:35.040 | when we go to the dentist from time to time.

00:48:36.840 | And the occasional x-ray might be safe

00:48:39.240 | depending on who you are,

00:48:40.240 | provided you're not pregnant, et cetera.

00:48:42.400 | I've gone to the dentist,

00:48:43.760 | they put you in the chair,

00:48:44.600 | they cover you with a lead blanket,

00:48:45.720 | and then they run behind the screen to protect themselves

00:48:49.800 | and they beam you with the x-rays

00:48:51.160 | to get a picture of your teeth and your jaws

00:48:52.800 | and your skull, et cetera.

00:48:54.540 | Well, if you were to get too many x-rays,

00:48:57.280 | you could severely damage the tissues of your body,

00:49:00.360 | but you don't experience any pain during the x-ray itself.

00:49:03.760 | In contrast, you can think that your body is damaged

00:49:09.980 | and experience extreme pain,

00:49:12.760 | and yet your body can have no damage.

00:49:16.720 | A classic example of this was published

00:49:18.840 | in the British Journal of Medicine

00:49:20.840 | in which a construction worker fell from,

00:49:24.080 | I think it was a second story which he was working,

00:49:27.440 | and a nail went up and through his boot.

00:49:31.980 | And he looked down and he saw the nail

00:49:35.020 | going through his boot,

00:49:36.520 | and he was in absolute excruciating pain.

00:49:39.820 | They took him to the hospital,

00:49:42.880 | and because the nail was so long

00:49:44.880 | and because of where it had entered and exited the boot,

00:49:47.660 | they had to cut away the boot in order to get to the nail.

00:49:52.160 | And when they did that,

00:49:53.240 | they revealed that the nail had passed

00:49:55.080 | between two of his toes.

00:49:56.840 | It had actually failed to impale his body in any way.

00:50:01.840 | And yet the view, the perception of that nail

00:50:04.880 | entering his boot at one end

00:50:06.920 | and exiting the boot at the other

00:50:08.460 | was sufficient to create the experience of a nail

00:50:12.360 | that had gone through his foot.

00:50:14.320 | And the moment he realized

00:50:16.040 | that that nail had not gone through his foot,

00:50:18.740 | the pain completely evaporated.

00:50:20.760 | And this has been demonstrated numerous times.

00:50:22.980 | People that work in emergency rooms

00:50:24.560 | actually see variations on this, not always that extreme,

00:50:28.000 | but many times what we see

00:50:30.520 | and how we perceive that wound or that event

00:50:33.700 | has a profound influence on how we experience pain.

00:50:36.560 | And I mention this not just because

00:50:38.720 | it's a kind of sensational and fantastic example

00:50:41.160 | of this extreme subjective nature of pain,

00:50:43.580 | but also because it brings us back to this element,

00:50:46.280 | which is we don't know how other people feel,

00:50:49.520 | not just about pain, but about pleasure.

00:50:51.680 | We think we do.

00:50:53.500 | We have some general sense of whether or not an event

00:50:56.440 | ought to be painful or pleasurable,

00:50:58.780 | but actually we barely understand how we feel,

00:51:01.960 | let alone how other people feel.

00:51:03.660 | And we can be badly wrong about how we feel,

00:51:07.260 | meaning we can misinterpret our own sense of pain

00:51:11.020 | or our own sense of pleasure

00:51:12.800 | depending on what we see with our eyes

00:51:15.400 | and what we hear with our ears.

00:51:17.340 | So we hear a scream, like a shrill scream,

00:51:20.800 | and we think it must be pain.

00:51:22.840 | And if we look at something that's happening to somebody

00:51:24.880 | and it fits a prior category or a prior representation

00:51:28.460 | of what we would consider painful stimulus,

00:51:31.140 | well, then we think that they're in extreme pain,

00:51:34.200 | but actually they might not be in pain at all.

00:51:36.600 | Now, this highly subjective nature of pain

00:51:39.280 | and the way in which we use our visual system

00:51:41.600 | to interpret other people's pain and our own pain

00:51:45.040 | has actually been leveraged

00:51:46.840 | to treat a very extreme form of chronic pain.

00:51:50.880 | And it's an absolutely fascinating area

00:51:53.120 | of biology and neuroscience.

00:51:54.640 | And it's one that we can actually all leverage

00:51:57.200 | toward reducing our own levels of pain

00:52:00.000 | whenever we are injured,

00:52:01.400 | or believe it or not, even in chronic pain.

00:52:04.580 | To describe this area of science

00:52:06.120 | requires a kind of extreme example,

00:52:08.840 | but I want to be clear that even if you don't suffer

00:52:11.400 | from this extreme example,

00:52:13.520 | there's relevance and a tool to extract for you.

00:52:17.160 | The extreme example is that of an amputated digit,

00:52:20.880 | meaning one of your fingers or your toes,

00:52:23.680 | or of an amputated limb.

00:52:25.980 | So people that have digits or limbs that are gone,

00:52:30.980 | missing from an injury or surgical removal,

00:52:34.800 | will often have the experience that it's still there,

00:52:37.800 | the so-called phantom limb phenomenon.

00:52:41.100 | Now, why would that be?

00:52:42.720 | Well, when you remove a particular finger or limb,

00:52:46.980 | obviously that finger and limb is gone,

00:52:50.200 | and the dorsal root ganglion neuron

00:52:52.600 | that would normally send a wire

00:52:54.640 | out to that particular region of the body,

00:52:57.140 | that wire is no longer there

00:52:58.420 | because that portion of the body is no longer there.

00:53:00.820 | And in some cases, those neurons die,

00:53:03.500 | almost always, but not always.

00:53:05.840 | However, the map, your so-called homunculus,

00:53:08.600 | your representation of yourself in the brain

00:53:12.300 | is still there.

00:53:13.340 | And this map, the so-called homunculus map

00:53:17.640 | that you have and that I have is very plastic.

00:53:20.500 | It can change.

00:53:21.600 | And so as a consequence,

00:53:23.840 | areas of the map that are adjacent to one another

00:53:26.680 | can actually start to invade other areas of the map.

00:53:31.300 | So for instance, there are neuroimaging studies

00:53:34.840 | that have documented that somebody that has, say,

00:53:37.400 | a complete removal of their left arm,

00:53:40.800 | the representation of their left arm

00:53:43.320 | still exists in the cortex.

00:53:45.880 | And experimentally, if one is to stimulate

00:53:48.960 | that area of the cortex, that person,

00:53:52.180 | and if that person were you,

00:53:53.620 | would experience having that arm,

00:53:55.900 | that it were being stimulated, even though it's not there.

00:53:59.060 | Now, someone who has an amputated arm

00:54:00.920 | doesn't need to have their brain stimulated

00:54:03.280 | in order to have the experience

00:54:04.960 | of that phantom limb being present.

00:54:06.920 | In fact, many people who have limbs that were amputated

00:54:10.840 | feel as if that limb is still present,

00:54:13.600 | even though obviously it's not.

00:54:15.520 | And no matter how many times they look to the stump

00:54:18.120 | and just see a stump, somehow it doesn't reorganize

00:54:21.820 | that homunculus so-called central brain map.

00:54:25.060 | Now, that would be fine.

00:54:28.560 | You might even think that would be better,

00:54:29.880 | better to think you have the arm there

00:54:31.920 | than to feel as if it's missing.

00:54:34.200 | And yet many people who have amputated limbs

00:54:36.880 | report phantom limb pain.

00:54:39.180 | They don't feel that the arm

00:54:40.400 | is just casually draped next to them.

00:54:42.500 | They feel as if it's bunched up and it's an extreme pain.

00:54:45.520 | In fact, this kind of contorted stance

00:54:49.440 | that I'm taking right here in my chair

00:54:50.940 | is not unlike the way that these patients describe this.

00:54:53.240 | They feel as if it's kind of cramped up.

00:54:55.240 | It's very uncomfortable for them.

00:54:57.600 | Now, an absolutely creative,

00:55:01.360 | and you could even say genius scientists

00:55:04.280 | by the name of Ramachandran, that's actually his last name.

00:55:07.660 | His complete name is a little bit more complicated.

00:55:09.940 | So you all almost always hear Ramachandran

00:55:12.680 | referred to as Ramachandran or VS Ramachandran

00:55:15.560 | because his full name is Vilayanur Subramanian Ramachandran.

00:55:20.560 | So a lot of letters in there, a lot of vowels.

00:55:23.320 | But Ramachandran is a neuroscientist.

00:55:26.960 | He was actually a colleague of mine

00:55:28.320 | when my lab was formerly

00:55:29.920 | at the University of California, San Diego.

00:55:32.000 | He's done a lot of work on this phantom limb phenomenon.

00:55:34.720 | And Ramachandran actually started off as a vision scientist.

00:55:37.460 | And he understood the power of the visual system

00:55:40.560 | in dictating our experience of things like pain and pleasure.

00:55:44.480 | And so what he developed was a very low technology

00:55:48.440 | yet neuroscientifically sophisticated treatment

00:55:52.020 | for phantom limb.

00:55:53.800 | It consisted of a box, literally a box

00:55:57.240 | that had mirrors inside of it.

00:55:59.440 | And the patient would put the intact hand or limb

00:56:03.320 | into one side.

00:56:05.000 | And obviously they couldn't put the amputated limb

00:56:07.300 | into the other side,

00:56:08.140 | but because of the configuration of the mirrors,

00:56:10.520 | it appeared as though they had two symmetric limbs

00:56:14.020 | inside the box.

00:56:15.440 | And then he would have them look at that limb

00:56:18.420 | and move it around.

00:56:20.220 | And as they would do this,

00:56:21.600 | they would report real-time movement,

00:56:25.080 | or I should say real-time perception of movement

00:56:27.480 | in the phantom limb.

00:56:29.120 | Now, this is absolutely incredible,

00:56:30.400 | but it makes total sense

00:56:31.720 | when you think about the so-called top-down

00:56:33.960 | or contextual modulation of our sensory experience.

00:56:37.440 | Remember, it's anticipation, it's anxiety,

00:56:39.960 | it's interpretation of what's happening

00:56:42.240 | that drives our perception of what's happening.

00:56:45.360 | And so as he would have these patients

00:56:48.680 | move their intact limb to a more relaxed position,

00:56:52.160 | the patients would feel as if the phantom limb

00:56:54.480 | were relaxing.

00:56:56.120 | And this was used successfully to treat phantom limb pain

00:56:59.120 | in a number of different people.

00:57:01.000 | It didn't always work.

00:57:02.200 | And you can imagine sometimes it might be a little trickier

00:57:04.120 | like for a leg,

00:57:04.960 | although there have been leg boxes

00:57:06.960 | that have been developed and arranged for this purpose.

00:57:11.480 | And what was remarkable

00:57:12.980 | is that they could finish these experiments

00:57:14.680 | and have the patient, the person,

00:57:17.640 | enter a state of relaxation,

00:57:19.480 | reduce the pain in the phantom limb,

00:57:21.240 | and it would stay there,

00:57:22.280 | even though, of course, as they exited the mirror box,

00:57:25.980 | they would go about their life

00:57:27.360 | and use their intact limb for its various purposes.

00:57:30.600 | I love this experiment because it really speaks

00:57:32.640 | to the subjective nature of pain and pleasure.

00:57:35.480 | It speaks to the power of the visual system,

00:57:37.500 | like what we see,

00:57:38.560 | just like the nail-through-the-boot experiment,

00:57:40.220 | what we see profoundly impacts our experience

00:57:44.340 | of pleasure and pain, in this case, pain.

00:57:47.120 | Now, there's another aspect to the phantom limb experience

00:57:52.040 | and of these maps, the so-called homunculus maps

00:57:54.740 | in the cortex that Ramachandran worked on,

00:57:57.840 | which is very interesting

00:57:59.480 | and reveals the degree to which these maps are plastic

00:58:02.860 | or can change in response to experience.

00:58:06.400 | Turns out that because of the locations

00:58:10.520 | of different body part representations within these maps,

00:58:14.860 | certain parts of our body

00:58:16.280 | that normally we don't think of as related

00:58:18.880 | can start to create merged experiences.

00:58:23.000 | What do I mean by that?

00:58:24.220 | Well, Ramachandran described a patient

00:58:27.400 | who had a somewhat odd experience

00:58:31.120 | of having lost their foot.

00:58:33.160 | So they actually had their foot amputated

00:58:35.760 | about midway up the Achilles,

00:58:37.340 | so lower portion of the calf and foot.

00:58:41.080 | I don't recall what the reason was for having it removed.

00:58:44.240 | And fortunately for this patient,

00:58:45.960 | they did not experience pain in that portion of their body,

00:58:50.240 | but rather they confided in him

00:58:53.240 | that whenever they would have sex,

00:58:56.780 | they would experience their orgasm in their phantom foot

00:59:01.160 | in addition to in their genitals, of course.

00:59:03.780 | And Ramachandran understood the homunculus map

00:59:07.220 | and he understood that this was because

00:59:09.660 | the representation of the foot within the homunculus

00:59:12.800 | actually lies adjacent to

00:59:14.720 | and is somewhat interdigitated with,

00:59:17.140 | it actually kind of merges with

00:59:20.020 | the representation of the genitalia.

00:59:22.840 | Now, that's a weird situation.

00:59:26.440 | And yet you now know that the density of innervation

00:59:30.920 | of the feet and the genitalia,

00:59:32.680 | as well as the lips and the face,

00:59:34.260 | are actually the highest sensory innervation

00:59:37.840 | that you have in your entire body.

00:59:39.600 | And this speaks to, I think,

00:59:41.480 | a more important general principle for all people

00:59:44.480 | of the experience of pleasure or pain,

00:59:46.800 | which is that an aspect of our pain or pleasure

00:59:50.160 | can be highly localized, right?

00:59:52.680 | It can be because of a cut to a particular location

00:59:54.840 | on the body, or it can be because, excuse me,

00:59:58.940 | of a fall injury or a kind of bruise

01:00:02.760 | on one side of our body.

01:00:04.080 | And yet our experience of pleasure and pain

01:00:06.940 | can also be an almost body-wide experience.

01:00:11.160 | And yet it's always most rich,

01:00:13.800 | it's always most heightened in these regions of our body

01:00:16.400 | that have dense sensory innervation.

01:00:19.140 | So we experience pain and pleasure

01:00:20.900 | according to local phenomenon, receptors in the skin

01:00:23.760 | and this homunculus map

01:00:24.960 | that has all these different territories.

01:00:26.960 | But because of the way that those territories are related,

01:00:29.900 | this kind of wild example of somebody experiencing orgasm

01:00:33.440 | in their phantom foot speaks to the larger experience,

01:00:36.620 | the more typical, rather, experience that I should say,

01:00:39.540 | that all people have,

01:00:41.120 | which is that pleasure can be body-wide,

01:00:44.120 | or we can experience it in our face,

01:00:46.520 | the bottoms of our feet and other areas of the body

01:00:49.100 | that we experience pleasure.

01:00:50.360 | And similarly with pain.

01:00:52.080 | And that brings us to the topic of whole body pain,

01:00:55.220 | not just localized pain,

01:00:56.880 | as well as whole body pleasure, not just localized pleasure.

01:01:01.420 | There are a number of examples of whole body pain

01:01:05.160 | that people suffer from.

01:01:06.360 | And one common one is called fibromyalgia.

01:01:09.760 | I want to just first share with you

01:01:12.240 | a little bit of medical insight.

01:01:14.120 | A few months back, I did an Instagram Live

01:01:17.000 | with Dr. Sean Mackey, who's an MD, medical doctor,

01:01:20.940 | and a PhD at Stanford School of Medicine.

01:01:23.640 | That was recorded and placed on my Instagram.

01:01:26.180 | If you want to check it out,

01:01:27.440 | we can provide a link to that in the show notes.

01:01:30.140 | Dr. Mackey is the chief of the division of pain

01:01:34.060 | at Stanford School of Medicine.

01:01:35.900 | So he's a scientist, he studies pain,

01:01:38.280 | and he treats patients dealing with various forms of pain,

01:01:41.380 | whole body pain like fibromyalgia, acute pain, et cetera.

01:01:45.200 | And he shared with me something very interesting,

01:01:47.120 | which is that anytime you hear or see the word syndrome,

01:01:52.120 | that means that the medical establishment

01:01:54.680 | does not understand what's going on.

01:01:56.560 | A syndrome is a constellation of symptoms

01:01:58.920 | that point in a particular direction

01:02:02.200 | or some general set of directions

01:02:03.820 | about what could be going on,

01:02:05.480 | but it doesn't reveal a true underlying disease necessarily.

01:02:10.480 | It could be a aggregate of diseases,

01:02:12.840 | or it could be something else entirely.

01:02:15.320 | And I want to make sure that I emphasize

01:02:18.660 | the so-called psychosomatic phenomenon.

01:02:21.360 | I think sometimes we hear psychosomatic

01:02:23.560 | and we interpret that as meaning all in one's head,

01:02:26.580 | but I think it's important to remember

01:02:28.360 | that everything is neural,

01:02:29.560 | whether or not it's pain in your body

01:02:31.360 | 'cause you have a gaping wound

01:02:33.640 | and you're hemorrhaging out of that wound,

01:02:35.600 | or whether or not it's pain for which you cannot explain it

01:02:40.120 | on the basis of any kind of injury, it's all neural.

01:02:42.640 | So saying body, brain, or psychosomatic,

01:02:45.920 | it's kind of irrelevant,

01:02:47.320 | and I hope someday we move past that language.

01:02:49.680 | Psychosomatic is interesting.

01:02:53.100 | There was a paper that was published in 2015,

01:02:57.200 | and then again in 2020, a different paper

01:03:00.480 | focused on the so-called psychogenic fevers

01:03:03.760 | or psychosomatic effects.

01:03:05.000 | I just briefly want to mention this

01:03:06.380 | because it relates back to pain.

01:03:08.660 | These studies have shown that there are areas

01:03:11.760 | of the so-called thalamus,

01:03:13.000 | which integrates and filters sensory information

01:03:15.720 | of different kinds,

01:03:17.200 | and within the brainstem, an area called the DMH,

01:03:21.460 | and I can also provide a link to this study if you like,

01:03:24.020 | that shows that there is a true neurological basis.

01:03:28.080 | There are brain areas and circuits

01:03:30.220 | that are related to what's called psychogenic fever.

01:03:32.920 | When we are stressed,

01:03:34.420 | and in particular, if we think that we were injured

01:03:37.580 | or that we were infected by something,

01:03:39.780 | we can actually generate a true fever.

01:03:43.060 | It is not an imagined fever.

01:03:45.220 | It is our thinking generating an increase

01:03:48.880 | in body temperature.

01:03:50.620 | And so this has been called psychosomatic,

01:03:52.600 | it's been called psychogenic,

01:03:54.260 | but it has a neural basis, okay?

01:03:56.740 | So when we hear syndrome

01:03:59.100 | and a patient comes into a clinic

01:04:01.420 | and says that they suffer, for instance,

01:04:03.660 | from something which is very controversial, frankly,

01:04:06.120 | like chronic fatigue syndrome,

01:04:07.700 | some physicians believe that it reflects

01:04:10.020 | a real underlying medical condition, others don't.

01:04:13.820 | However, syndrome means we don't understand,

01:04:18.180 | and that doesn't mean something doesn't exist.

01:04:21.260 | Fibromyalgia or whole body pain for a long time

01:04:25.300 | was written off or kind of explained away

01:04:28.580 | by physicians and scientists, frankly,

01:04:30.920 | my community, as one of these syndromes.

01:04:34.340 | It couldn't be explained.

01:04:35.480 | However, now there is what I would consider,

01:04:38.720 | and I think others would and should consider,

01:04:41.840 | firm understanding of at least one of the bases

01:04:45.060 | for this whole body pain.

01:04:46.860 | And that's activation of a particular cell type called glia.

01:04:51.860 | And there's a receptor on these glia,

01:04:53.740 | for those of you that want to know,

01:04:54.700 | called the toll-4 receptor.

01:04:57.060 | And activation of the toll-4 receptor

01:05:00.200 | is related to certain forms of whole body pain

01:05:03.020 | and fibromyalgia.

01:05:04.920 | Now, what treatments exist for fibromyalgia?

01:05:08.440 | And even if you don't suffer from fibromyalgia,

01:05:10.740 | and even if you don't know anyone who does,

01:05:13.140 | this is important information,

01:05:14.440 | because what I'm about to tell you

01:05:15.660 | relates to how you and your body, which is you, of course,

01:05:20.660 | can deal with pain of any kind.

01:05:23.060 | And there are actually things that one can do and take

01:05:26.520 | that can encourage nerve health in general,

01:05:29.540 | in other conditions like diabetic neuropathy,

01:05:31.740 | but in all individuals.

01:05:34.100 | So there are clinical data using a prescription drug.

01:05:39.100 | This is work that actually was done

01:05:41.520 | by Dr. Mackey and colleagues.

01:05:43.900 | The drug is called naltrexone.

01:05:45.340 | Naltrexone is actually used for the treatment

01:05:47.480 | of various opioid addictions and things of that sort.

01:05:51.740 | But it turns out that a very low dose,

01:05:54.460 | I believe it was a 1/10 the size of the typical dose

01:05:58.760 | of naltrexone, has been shown to have some success

01:06:03.320 | in dealing with and treating certain forms of fibromyalgia.

01:06:06.620 | And it has that success because of its ability

01:06:09.480 | to bind to and block these TOL4 receptors on glia.

01:06:14.160 | Okay, so this so-called syndrome,

01:06:16.180 | or this thing that previously was called a syndrome,

01:06:18.020 | fibromyalgia, actually has a biological basis.

01:06:21.180 | It was not just in patients' heads.

01:06:23.620 | And I really tip my hat to the medical establishment,

01:06:26.540 | including Dr. Mackey and others,

01:06:28.420 | who explored the potential underlying biologies

01:06:32.020 | of things like fibromyalgia,

01:06:33.220 | and they're starting to arrive at treatments.

01:06:34.980 | Now, I'm not a physician, I'm a professor,

01:06:37.040 | so I'm not prescribing anything.

01:06:38.560 | You should talk to your doctor, of course,

01:06:39.940 | if you have fibromyalgia or other forms of chronic

01:06:43.120 | or whole body pain to explore whether or not

01:06:45.460 | these low dose naltrexone treatments are right for you.

01:06:48.820 | But I think it's a beautiful case study, if you will,

01:06:51.600 | not a case study of an individual patient,

01:06:53.300 | but a case in study of linking up the patient's self-report

01:06:58.300 | of these experiences and using science

01:07:00.740 | to trying to establish clinical treatments.

01:07:03.460 | There's another treatment, or I should say,

01:07:05.800 | there's another approach that one could take.

01:07:07.720 | And again, I'm not recommending people do this necessarily.

01:07:10.180 | You have to determine what's right and safe for you.

01:07:12.260 | I cannot do that.

01:07:13.420 | There's no way, your situation's very far too much,

01:07:15.940 | and it would be outside of my wheelhouse

01:07:18.260 | to prescribe anything.

01:07:19.680 | But there's a particular compound,

01:07:22.820 | which in the United States is sold over the counter,

01:07:25.140 | and in Europe is prescription.

01:07:26.700 | It's one that I've talked about on this podcast before

01:07:28.940 | for other purposes, and that compound is acetyll-carnitine.

01:07:33.940 | Acetyll-carnitine, as I mentioned,

01:07:35.980 | is by prescription in most countries in Europe.

01:07:38.500 | In the US, you can buy this over the counter.

01:07:41.220 | There is evidence that acetyll-carnitine

01:07:44.180 | can reduce the symptoms of chronic whole body pain

01:07:46.900 | and other certain forms of acute pain

01:07:49.940 | at dosages of somewhere between one to three

01:07:53.100 | and sometimes four grams per day.

01:07:55.440 | Now, acetyll-carnitine can be taken orally.

01:07:58.020 | It's found in 500 milligram capsules,

01:08:00.740 | as well as by injection.

01:08:03.260 | By injection in the States, in the United States that is,

01:08:06.620 | also requires a prescription,

01:08:08.320 | or requires a prescription, I should say.

01:08:10.900 | The over the counter forms are generally capsules

01:08:13.220 | or powders.

01:08:14.500 | Those apparently do not require a prescription.

01:08:17.580 | There are several studies exploring acetyll-carnitine

01:08:20.460 | in this context, as well as for diabetic neuropathy.

01:08:23.940 | And what's interesting about acetyll-carnitine

01:08:25.860 | is it's one of the few compounds that isn't just used

01:08:30.020 | for the treatment of pain,

01:08:31.620 | but has also been shown in certain contexts

01:08:34.180 | to improve peripheral nerve health generally.

01:08:37.760 | And for that reason, it's an interesting compound.

01:08:40.460 | I've also talked about acetyll-carnitine on here previously

01:08:43.660 | because it has robust effects on things like

01:08:46.820 | sperm motility and health,

01:08:49.460 | including the speeds at which sperm swim,

01:08:52.920 | how straight they swim.

01:08:54.000 | Turns out that swimming for sperm is more efficient

01:08:57.440 | if they swim straight, as opposed to like those,

01:09:00.420 | you know, like those kids on the swim team,

01:09:02.420 | they're like banging up against the lane lines

01:09:04.080 | and zigzagging all over the place.

01:09:06.180 | So it does turn out to be the case that the quickest route

01:09:10.680 | between any two places is a straight line.

01:09:12.880 | And the good sperm know that,

01:09:14.440 | and the less good sperm don't seem to know that.

01:09:16.440 | And acetyll-carnitine seems to facilitate

01:09:18.740 | straight swimming trajectories,

01:09:20.540 | as well as speed of swimming and overall sperm health.

01:09:23.140 | And there is evidence from quality peer-reviewed studies

01:09:26.740 | showing that acetyll-carnitine supplementation

01:09:29.460 | can also be beneficial for women's fertility

01:09:32.260 | in ways that it affects perhaps,

01:09:34.460 | we don't really know the mechanism,

01:09:36.580 | health and status of the egg or egg implantation.

01:09:39.740 | There are a large number of studies on acetyll-carnitine.

01:09:42.180 | You can look those up on PubMed, if you like,

01:09:44.660 | or on examine.com.

01:09:46.660 | There are some studies that I don't think are included there

01:09:49.180 | which are particularly interesting.

01:09:50.380 | One that I just would like to reference.

01:09:53.140 | The last name of the first author is Mahdavi,

01:09:58.140 | so M-A-H-D-A-V-I.

01:10:01.260 | The title of the paper is

01:10:02.540 | effects of L-carnitine supplementation

01:10:04.780 | on serum inflammatory markers

01:10:07.020 | and matrix metalloprotease enzymes

01:10:09.740 | in females with knee osteoarthritis.

01:10:12.100 | So this is a randomized, double-blind,

01:10:13.860 | placebo-controlled pilot study

01:10:15.540 | that showed really interesting effects

01:10:17.680 | of short-term supplementation of acetyll-carnitine.

01:10:21.420 | Longer term, the effects were less impressive.

01:10:24.200 | So it's pretty interesting that this compound

01:10:26.180 | has so many different effects.

01:10:27.220 | How could it have these effects?

01:10:28.340 | Well, it appears that it's having these effects

01:10:30.360 | through its impact on the so-called inflammatory cytokines.

01:10:35.040 | Inflammatory cytokines, for those of you that don't know,

01:10:38.000 | are secreted by the immune system

01:10:39.720 | in response to different stressors,

01:10:42.060 | physical stressors, mental stressors too,

01:10:44.660 | food that you eat that isn't good for you.

01:10:47.740 | The so-called hidden sugars, yes,

01:10:49.520 | will increase inflammation if they're ingested too often

01:10:53.240 | or in amounts that are too high in quantity.

01:10:55.720 | Things like interleukin-1 beta,

01:10:57.920 | things like C-reactive protein,

01:10:59.720 | things like interleukin-6.

01:11:01.240 | Interleukin-6 is kind of the generic inflammatory marker

01:11:04.240 | that all studies refer to.

01:11:05.480 | And yet there are other interleukins.

01:11:07.460 | Please note that there are other interleukins

01:11:09.920 | like interleukin-10 that are anti-inflammatory.

01:11:13.400 | So your immune system can secrete inflammatory molecules

01:11:16.520 | to deal with wounds and stress and things.

01:11:18.720 | And in the short term, that's good.

01:11:19.920 | And in the long term, that's bad.

01:11:21.600 | And it can secrete anti-inflammatory cytokines like IL-10.

01:11:26.600 | And these matrix metalloproteases, it's kind of a mouthful,

01:11:30.660 | but these matrix metalloproteases are very interesting.

01:11:33.000 | Anytime you see ACE, that's generally an enzyme,

01:11:37.360 | which means that these compounds, in this case,

01:11:40.840 | these matrix metalloproteases are used to break down

01:11:43.960 | certain elements around wounds and scarring,

01:11:48.480 | which might sound like a bad thing,

01:11:49.760 | but in some cases is good because it allows certain cells,

01:11:53.140 | like glial cells, so-called microglia,

01:11:55.040 | to come in like little ambulances,

01:11:56.520 | like little paramedics, and clean up wounds.

01:11:59.360 | So scarring and inflammation is kind of a double-edged sword.

01:12:02.580 | It can be good, but too much scarring,

01:12:05.100 | if it contains a wound too much,

01:12:06.820 | doesn't allow the infiltration of cell types

01:12:09.000 | to move in and take care of that wound and heal it up.

01:12:11.720 | So it appears that L-carnitine is impacting

01:12:14.200 | a number of different processes, both to impact pain

01:12:17.040 | and perhaps, and I want to underscore perhaps,

01:12:19.160 | but there are good studies happening now,

01:12:21.240 | perhaps accelerate wound healing as well.

01:12:25.640 | As long as we're talking about acute pain and chronic pain

01:12:28.200 | and supplementation and non-prescription drugs,

01:12:31.000 | at least in the United States, that people can take

01:12:32.760 | to deal with pain of various kinds,

01:12:34.940 | I'd be remiss if I didn't mention the two

01:12:36.880 | that I get asked most often about, which are Agmatine

01:12:40.680 | and S-adenosylmethionine, which is sometimes called SAMe.

01:12:46.960 | Both of those have been shown to have some impact,

01:12:50.340 | categorized on examine as notable impact

01:12:54.480 | on various forms of pain due to osteoarthritis

01:12:58.160 | or due to injury of various kinds

01:13:00.800 | in different subject population, men, women,

01:13:03.120 | people of different ages, et cetera.

01:13:05.320 | SAMe in particular has been interesting

01:13:07.660 | because it's been shown head-to-head with drugs

01:13:10.880 | like naproxen and other drugs of that sort,

01:13:14.300 | which are well established and sold over the counter

01:13:17.820 | in the US to work at least as well

01:13:20.980 | as some of those compounds at certain dosages.

01:13:23.980 | But it's also been shown that SAMe

01:13:27.020 | and some of those things take more time

01:13:29.220 | in order to have those effects.

01:13:31.500 | In fact, head-to-head with things like naproxen

01:13:34.580 | have been shown that they can take up to a month

01:13:37.060 | in order to have the pain relieving effect.

01:13:39.260 | Now, whether or not that makes them a better choice

01:13:40.940 | or a worse choice really depends on your circumstances.

01:13:43.620 | I'm certainly not recommending that anybody take anything,

01:13:46.300 | but I do think it's interesting and important to point out

01:13:48.900 | that things like agmatine, things like SAMe

01:13:51.340 | have been shown under certain circumstances

01:13:54.040 | to be beneficial for pain

01:13:55.600 | and they are outside the realm of prescription drugs.

01:13:57.980 | And I think this is a growing area of,

01:14:00.220 | some people call them supplements,

01:14:01.300 | some people call them nutraceuticals.

01:14:03.460 | Look, at the end of the day,

01:14:04.400 | these are compounds that affect cellular processes

01:14:06.920 | and the more that we understand

01:14:07.900 | how they affect those cellular processes

01:14:09.980 | as we now do for things like acetyl-L-carnitine,

01:14:13.060 | I think the more trust that we can put into them

01:14:15.420 | or the more to which we might want to avoid them

01:14:19.100 | because of some of the side effects or contraindications

01:14:21.700 | that those compounds could have.

01:14:23.320 | If you're interested in those other compounds,

01:14:25.680 | I do invite you, as I always do, to check out examine.com,

01:14:28.760 | but also to do your research on those compounds

01:14:31.400 | by simply putting them into Google

01:14:33.020 | or putting them into PubMed, which would be even better.

01:14:35.340 | And if you are going to go into PubMed,

01:14:37.180 | if you're going to start playing scientist,

01:14:39.120 | which I do encourage you to do,

01:14:41.220 | I would encourage you to not just read abstracts,

01:14:43.580 | but if you can, if the studies are freely available,

01:14:45.820 | I realize not all of them are freely available,

01:14:48.040 | to try and read those studies,

01:14:49.220 | at least to the extent that you can.

01:14:51.660 | There's a particularly nice study that you might look at

01:14:54.020 | that was published in 2010 in Pain Medicine,

01:14:57.420 | which is K-Nan et al., K-E-Y-N-A-N,

01:15:01.420 | which looked at the safety and efficacy

01:15:03.300 | of dietary-agmentine sulfate

01:15:05.460 | on lumbar disc-associated radiculopathy.

01:15:10.760 | I'm not laughing at the condition.

01:15:12.880 | It's a painful condition that describes,

01:15:16.880 | it's kind of a range of symptoms

01:15:18.420 | that relate to pinching of nerves.

01:15:20.160 | The spinal columns, I was laughing at my pronunciation of it.

01:15:23.120 | That particular study is quite good.

01:15:25.520 | And the conclusion of that study that they drew

01:15:28.520 | was that there were limited side effects

01:15:31.520 | and that dietary-agmentine sulfate

01:15:33.680 | is safe and efficacious for treating and alleviating pain

01:15:36.620 | and improving quality of life in lumbar disc-associated pain.

01:15:40.840 | However, there were very specific dosage regimens, excuse me,

01:15:45.840 | that were described there and duration of treatment.

01:15:48.220 | And so you should not take anything that I say

01:15:50.360 | or that study to mean that you can just take this stuff

01:15:52.460 | willy-nilly or at any concentration, of course, or dose.

01:15:55.980 | You always want to pay attention to what the science says.

01:15:59.280 | That paper, fortunately, is freely available online

01:16:02.000 | and we will also provide a link to that study.

01:16:04.220 | For those of you that are interested in SAM-E

01:16:06.460 | and its usage for the treatment of various types of pain

01:16:10.140 | and perhaps other benefits,

01:16:11.840 | a number of companies have stopped making SAM-E.

01:16:15.860 | Instead, what they're now focusing on

01:16:18.280 | is what they think is a better

01:16:20.180 | or more bioavailable alternative,

01:16:22.700 | which is 5-methyl tetrahydrofolate or 5-MTHF.

01:16:27.700 | This molecule is necessary for converting homocysteine

01:16:33.520 | to methionine, which is then converted to SAM-E.

01:16:37.280 | So rather than taking SAM-E directly,

01:16:40.560 | the idea is to take something that's upstream of SAM-E

01:16:43.640 | and make more SAM-E endogenously available.

01:16:46.540 | This is a different strategy.

01:16:47.960 | I've talked about this strategy before

01:16:49.840 | for increasing other things like growth hormone, et cetera.

01:16:53.240 | There's always this question of whether or not

01:16:55.400 | in trying to increase the amount

01:16:56.920 | of a particular molecule in the body,

01:16:58.560 | whether or not taking that specific molecule

01:17:00.440 | is the best thing or working further upstream

01:17:03.600 | as it's referred to, working on the precursor

01:17:07.240 | or increasing the levels of the precursor

01:17:09.040 | is the better way to go.

01:17:10.240 | It appears that this 5-MTHF is the strategy

01:17:16.100 | that people are now taking

01:17:18.240 | in place of taking SAM-E directly.

01:17:21.180 | So in other words, they're taking this

01:17:22.360 | in order to get elevated levels of SAM-E.

01:17:25.400 | Now I'd like to turn our attention

01:17:26.780 | to a completely non-drug, non-supplement related approach

01:17:31.540 | to dealing with pain.

01:17:33.060 | And it's one that has existed for thousands of years.

01:17:36.920 | And that only recently has the Western scientific community

01:17:41.140 | started to pay serious attention to,

01:17:43.780 | but they have started to pay serious attention to it.

01:17:46.800 | And there is terrific mechanistic science

01:17:49.980 | to now explain how and why acupuncture can work very well

01:17:55.560 | for the treatment of certain forms of pain.

01:17:58.060 | Now, first off, I want to tell you what was told to me

01:18:01.560 | by our director or chief of the pain division

01:18:04.440 | at Stanford School of Medicine, Dr. Sean Mackey,

01:18:06.980 | which was that some people respond very well to acupuncture

01:18:11.740 | and others do not.

01:18:13.540 | And the challenge is identifying who will respond well

01:18:17.440 | and who won't respond well.

01:18:19.720 | Now, when I say won't respond well,

01:18:21.240 | that doesn't necessarily mean that they responded

01:18:23.800 | in a negative way, that it was bad for them.

01:18:26.460 | But it does appear that a fraction of people

01:18:29.860 | experience tremendous pain relief from acupuncture

01:18:32.980 | and others experience none at all or very little

01:18:35.860 | to the point where they have to seek out

01:18:37.360 | other forms of treatment.

01:18:38.640 | The science on this is still ongoing.

01:18:42.620 | There's actually an excellent paper published on this

01:18:44.760 | in the Journal of the American Medical Association,

01:18:47.020 | one of the premier medical clinical journals.

01:18:50.580 | And it basically reinforced the idea

01:18:52.740 | that you have responders and non-responders.

01:18:55.200 | A number of laboratories have started to explore

01:18:59.000 | how acupuncture works.

01:19:01.220 | And one of the premier laboratories for this

01:19:03.700 | is Chufu Ma's lab at Harvard Medical School.

01:19:07.720 | Chufu has spent many years studying the pain system

01:19:11.440 | and a system that's related to the pain system,

01:19:13.920 | which is the system that controls our sensation of itch.

01:19:17.580 | Just as a brief aside about itch,

01:19:21.180 | itch and pain are often co-associated with one another.

01:19:25.440 | I was recently in Texas and I will tell you,

01:19:27.620 | they have some mean mosquitoes.

01:19:29.960 | They're small, but whatever they're injecting

01:19:32.540 | into your skin, well, here I am talking now

01:19:34.700 | about my subjective experience of pain.

01:19:36.140 | Whatever they injected into my skin felt to me

01:19:39.380 | like the most extreme mosquito bites I've ever had.

01:19:43.140 | Not while they were biting me,

01:19:44.780 | not while they were injecting the venom,

01:19:46.160 | but boy, do those Texan mosquitoes make me itch.

01:19:50.580 | How do they do it?

01:19:51.420 | Well, their venom creates little packets

01:19:55.500 | of so-called histamine that travel around.

01:19:58.400 | Those packets are called mast cells,

01:20:01.040 | little packets of histamine that go to that location

01:20:03.340 | and make me, and presumably you,

01:20:05.580 | want to scratch those mosquito bites.

01:20:07.820 | I scratch mine, you scratch yours,

01:20:09.040 | but we both scratch our mosquito bites.

01:20:10.980 | And when we do that, the histamines are released,

01:20:13.140 | it gets red and inflamed and they itch even worse.

01:20:16.460 | The inflammation is actually caused by the histamine.

01:20:19.180 | Well, that experience of inflammation and pain and itch

01:20:24.180 | is what we call a pre-rogenic experience, okay?

01:20:30.020 | So we have pain, which is nociception, essentially.

01:20:33.660 | I know that the pain aficionados always get a little upset

01:20:36.220 | 'cause they say, oh, there's no such thing

01:20:37.520 | as a pain receptor.

01:20:38.700 | It's nociceptive receptors

01:20:40.100 | and pain is subjective experience.

01:20:41.740 | Yes, I acknowledge all that, but for fluency,

01:20:44.800 | let's just think about pain as a certain experience

01:20:47.520 | and itch as a separate experience,

01:20:49.060 | but they often exist together

01:20:50.420 | because those mosquito bites were what I would call painful,

01:20:54.860 | or at least not pleasant.

01:20:55.900 | They didn't just itch, they were also painful.

01:20:58.380 | And that's because itch brings with it inflammation

01:21:01.740 | and inflammation often brings with it pain relief,

01:21:04.780 | but it can also bring with it the sensation of pain.

01:21:07.660 | So itch and pain are two separate phenomenon.

01:21:10.620 | It was actually discovered

01:21:12.420 | through a really interesting phenomenon

01:21:14.300 | that relates to something that is actually consumed

01:21:16.640 | in supplement form, which is this tropical legume.

01:21:20.440 | It's actually a bean called mucuna purines.

01:21:23.640 | That's M-U-C-U-N-A, that's one word, P-R-U-I-E-N-S.

01:21:28.640 | Mucuna purines is a bean.

01:21:32.420 | It's this legume that this bean is 99% L-DOPA.

01:21:37.260 | It's dopamine, or rather it's the precursor to dopamine.

01:21:40.020 | And people buy this stuff and take it over the counter

01:21:42.400 | as ways to increase their levels of dopamine.

01:21:44.640 | It does make you feel really dopamine doubt.

01:21:47.820 | I mean, it makes you feel a little high

01:21:49.620 | and really motivated and really energetic,

01:21:52.360 | a lot like other drugs that will do that.

01:21:55.100 | I don't necessarily recommend taking mucuna purines.

01:21:57.780 | I personally don't like taking it.

01:21:59.980 | It doesn't make me feel good.

01:22:01.140 | I crash really hard when I take it.

01:22:03.840 | But on the outside of this bean is a compound

01:22:07.860 | that makes people itch, okay?

01:22:10.500 | So they remove this when you take it in supplement form.

01:22:12.620 | In fact, it's usually in capsule form.

01:22:14.540 | But the outside of this bean, it's like a hairy bean, right?

01:22:18.020 | And those little hairs contain a compound

01:22:21.360 | which was actually used to study

01:22:23.940 | and identify these itch receptors in the skin.

01:22:27.060 | So we don't have time to go into all the details of itch,

01:22:30.020 | but it's pretty interesting that you have these compounds

01:22:32.380 | out in nature that can make us itch.

01:22:33.980 | Inside them, they have dopamine.

01:22:35.520 | I mean, this is really weird,

01:22:36.500 | but plant compounds are really powerful.

01:22:38.860 | So don't let anyone tell you that

01:22:40.940 | because something's from a plant or an herb

01:22:42.820 | that it's not powerful.

01:22:44.340 | There are very powerful plant and herb compounds.

01:22:47.420 | Mucuna purines being one of them with dopamine on the inside

01:22:50.180 | and itchy stuff on the outside.

01:22:52.240 | Now, what does this all have to do with acupuncture?

01:22:54.580 | Well, Chufu Ma's lab has not just identified

01:22:58.720 | the itch pathway, these puridogens as they're called,

01:23:01.940 | which cause itch and the purigenic phenomenon

01:23:04.900 | of itch being separate from pain.

01:23:07.180 | His lab has also studied how acupuncture causes relief of,

01:23:12.740 | but also can exacerbate pain.

01:23:16.060 | Now, the form of acupuncture that they explored

01:23:18.040 | was one that's commonly in use called electroacupuncture.

01:23:20.660 | So this isn't just putting little needles

01:23:23.060 | into different parts of the body.

01:23:24.940 | These needles are able to pass an electrical current,

01:23:28.700 | not magically, but because they have a little wire

01:23:30.460 | going back to a device and you can pass electrical current.

01:23:32.740 | Here's what they found.

01:23:33.900 | There's a public, this is a study, excuse me,

01:23:36.020 | published in the journal Neuron, cell press journal,

01:23:38.300 | excellent journal, very high stringency.

01:23:40.460 | So what Chufu Ma's lab found was that

01:23:42.740 | if electroacupuncture is provided to the abdomen,

01:23:47.060 | to the stomach area, it creates activation

01:23:51.660 | of what are called the sympathetic ganglia.

01:23:53.380 | These have nothing to do with sympathy

01:23:55.020 | in the emotional sense, has to do with the stress response.

01:23:58.300 | Simpa just means together.

01:23:59.580 | So it activated a bunch of neurons along the spinal cord

01:24:02.580 | and the activation of these neurons involves noradrenaline

01:24:08.380 | and something called NPY, neuropeptide Y.

01:24:12.960 | The long and short of it is that stimulating the abdomen

01:24:15.580 | with electroacupuncture was either anti-inflammatory

01:24:20.580 | or it could cause inflammation.

01:24:22.600 | It could actually exacerbate inflammation

01:24:24.660 | depending on whether or not it was of low or high intensity.

01:24:28.780 | Now that makes it a very precarious technique

01:24:30.980 | and this may speak to some of the reason

01:24:33.340 | why some people report relief from acupuncture

01:24:36.280 | and others do not.

01:24:37.740 | However, they went a step further

01:24:39.660 | and stimulated other areas of the body

01:24:42.020 | using electroacupuncture.

01:24:43.220 | And what they found is that stimulation of the legs,

01:24:46.060 | of the hind limbs as it's called in animals

01:24:47.900 | and the legs in humans caused a circuit,

01:24:51.340 | a neural circuit to be activated that goes from the legs

01:24:55.120 | up to an area of the base of the brain called the DMV,

01:24:59.500 | not the DMH, which I mentioned earlier,

01:25:01.280 | but the DMV, like you go to the DMV,

01:25:04.340 | which is a miserable experience for most people,

01:25:06.220 | forgive me, DMV employees, but let's be honest,

01:25:09.280 | most people don't enjoy going to the DMV as patrons,

01:25:13.120 | but we have to, so we go.

01:25:14.980 | The DMV and low intensity stimulation,

01:25:19.420 | this electroacupuncture of the hind limbs,

01:25:22.100 | activated the DMV and activated the adrenal glands,

01:25:25.800 | which sit atop your kidneys

01:25:27.860 | and cause the release of what are called catecholamines.

01:25:31.820 | And those were strongly anti-inflammatory.

01:25:35.300 | In other words, electroacupuncture of the legs and feet

01:25:39.900 | can if done correctly be anti-inflammatory

01:25:43.060 | and reduce symptoms of pain.

01:25:45.100 | And can we think accelerate wound healing

01:25:48.380 | because activations of these catecholaminergic pathways

01:25:51.860 | can accelerate wound healing as well.

01:25:54.100 | So the takeaway from this is that

01:25:56.700 | while there are thousands of years

01:25:58.980 | and millions of subjects involved in

01:26:02.100 | explorations of electroacupuncture and acupuncture,

01:26:06.180 | Western medicine is starting to come into this

01:26:08.980 | and start to explore underlying mechanism.

01:26:11.020 | Now, for those of you that love acupuncture

01:26:13.260 | and are real proponents of it, it's worked for you.

01:26:17.060 | You might say, well, why does Western medicine

01:26:19.260 | even need to come into this?

01:26:20.300 | Why should they even be exploring this?

01:26:22.340 | But we should all be relieved that they are

01:26:24.360 | because what's starting to happen now

01:26:26.840 | is that as the mechanistic basis for this

01:26:29.500 | is starting to come to light, insurance coverage

01:26:33.900 | of things like acupuncture is starting to emerge as well.

01:26:38.100 | And this is in contrast to other therapies

01:26:40.340 | for which there's a lot of anecdotal evidence

01:26:42.980 | but very little mechanistic understanding.

01:26:45.140 | One example of that would be laser photobiomodulation,

01:26:48.600 | the use of lasers of different types really

01:26:52.360 | to treat pain and to accelerate wound healing.

01:26:54.660 | A lot of people claim that this can really help them.

01:26:57.540 | However, most places, at least in the States,

01:27:00.480 | won't cover this with insurance

01:27:01.760 | or don't perform this in standard clinics.

01:27:04.540 | And the reason is the underlying mechanism isn't known.

01:27:08.300 | I'm not going to get into the argument

01:27:09.660 | about whether or not mechanistic understanding

01:27:12.060 | should or should not be required

01:27:14.620 | in order to have insurance coverage of things that work.

01:27:17.760 | That's not what this is about.

01:27:19.080 | And that actually would be a boring discussion

01:27:21.300 | because I'm shouting at a tunnel through you

01:27:23.640 | and I wouldn't be able to hear you shout back

01:27:25.280 | no matter what your stance on that is.

01:27:27.180 | But just trust me when I say that I am both relieved

01:27:31.260 | and delighted to hear

01:27:32.860 | that excellent medical institutions like Stanford

01:27:35.980 | are starting to think about electro-acupuncture

01:27:38.820 | and how it can work,

01:27:39.720 | that places like Harvard Medical School

01:27:41.700 | are starting to explore this at a mechanistic level.

01:27:44.220 | And I do believe that there's an open-mindedness

01:27:46.800 | that's starting to emerge.

01:27:48.620 | For instance, the National Institutes of Health

01:27:51.980 | not only has an Institute for Mental Health

01:27:54.060 | and Cancer Research and an Eye Institute,

01:27:55.740 | but now Complementary Health, the so-called NCCIH,

01:27:59.660 | National Institutes of Complementary Health

01:28:01.940 | that is exploring things like electro-acupuncture,

01:28:04.600 | meditation, various supplements and things of those sort.

01:28:08.040 | I do think that we're entering a new realm

01:28:09.580 | in which things like pain and pain management

01:28:11.660 | will be met with more openness by all physicians.

01:28:14.780 | At least that's my hope.

01:28:15.940 | So please take that into consideration.

01:28:17.840 | Right now, the mechanistic evidence

01:28:20.500 | for laser photobiomodulation is not strong.

01:28:23.140 | One of the major issues or the barriers to that

01:28:27.260 | is that most of the studies that are out there

01:28:30.440 | were actually paid for by companies that build devices

01:28:35.440 | for laser photobiomodulation.

01:28:38.140 | And so we really need independent studies

01:28:40.340 | funded by federal institutions

01:28:41.900 | that have no bias or financial relationship

01:28:44.500 | in order to gain trust in whatever data happened to emerge.

01:28:48.740 | There is a technique that at one time

01:28:51.600 | was considered alternative,

01:28:53.020 | but now has a lot of mechanistic science

01:28:55.860 | to explain how it works.

01:28:57.260 | And it does indeed work for the treatment of chronic

01:29:01.300 | and also for acute pain.

01:29:03.820 | And that treatment is hypnosis, in particular, self-hypnosis.

01:29:08.700 | My colleague at Stanford, in fact, my collaborator,

01:29:12.140 | Dr. David Spiegel, our associate chair of psychiatry,

01:29:14.900 | has devoted his professional life

01:29:16.620 | to developing hypnosis tools that people can use

01:29:20.260 | to help them sleep better, focus better,

01:29:22.460 | stay motivated, et cetera.

01:29:24.700 | While most people hear hypnosis and they think,

01:29:26.620 | oh, this is staged hypnosis,

01:29:28.060 | people walking around like chickens

01:29:29.440 | or being forced to laugh or fall asleep on command, et cetera,

01:29:33.100 | this is completely different than all that.

01:29:34.580 | This is self-hypnosis.

01:29:35.900 | And there are now dozens, if not more,

01:29:39.580 | quality peer-reviewed studies

01:29:41.240 | published in excellent journals done by Dr. Spiegel

01:29:44.940 | and others at other universities.

01:29:47.540 | It really all has to do with how self-hypnosis

01:29:50.620 | can modulate activity of the prefrontal cortex

01:29:54.540 | and related structures like the insula.

01:29:57.180 | The prefrontal cortex is involved in our executive function,

01:30:02.180 | as it's called, our planning, our decision-making,

01:30:04.260 | but also how we interpret context,

01:30:07.140 | what the meaning of a given sensation is.

01:30:10.120 | And that's extremely powerful.

01:30:12.120 | Just want to remind everybody that the currency

01:30:14.980 | of the brain and body has not changed

01:30:16.980 | in hundreds of thousands of years.

01:30:18.660 | It's always been dopamine, serotonin, glutamate, GABA,

01:30:21.780 | testosterone, estrogen.

01:30:23.300 | What's changed are the contingencies,

01:30:25.540 | the events in the world that drive whether or not

01:30:28.020 | we get an increase or decrease in testosterone or estrogen,

01:30:31.060 | the events in the world that dictate whether or not

01:30:33.400 | we get an increase or a decrease in dopamine.

01:30:36.000 | Believe me, the events that drove those increases

01:30:38.720 | and decreases were very different

01:30:40.020 | even a hundred years ago than they are now.

01:30:42.460 | And as we create new things and societies change, et cetera,

01:30:45.860 | they will continue to exchange information

01:30:50.380 | in the same currency, which is dopamine, serotonin,

01:30:52.980 | and all these other neuromodulators and chemicals.

01:30:55.380 | Hypnosis takes advantage of this

01:30:58.020 | by allowing an individual, you if you like,

01:31:01.980 | to change the way that you interpret particular events

01:31:04.560 | and to actually experience what would be painful

01:31:06.940 | as less painful or not painful.

01:31:09.180 | And that's just the example of pain.

01:31:10.500 | Hypnosis is powerful for other reasons too.

01:31:12.860 | It actually can help rewire neural circuits

01:31:15.640 | so that you don't experience as much pain

01:31:18.120 | so that you can sleep faster, focus faster.

01:31:20.180 | If this is all sounding very fantastical,

01:31:23.500 | well, it's supported by data.

01:31:26.060 | The data are that when people do self-hypnosis,

01:31:30.020 | even brief self-hypnosis of 10 or 15 minutes

01:31:33.220 | a few times a week, maybe even return to that hypnosis

01:31:36.620 | by just using a one minute a day hypnosis,

01:31:39.340 | they can achieve significant and often very impressive

01:31:43.340 | degrees of pain relief and chronic pain,

01:31:46.180 | whether or not that chronic pain arises

01:31:47.720 | through things like fibromyalgia or through other sources.

01:31:50.620 | If you want to check this out,

01:31:52.120 | there's a wonderful zero cost resource

01:31:54.140 | that's grounded in this work.

01:31:56.220 | It's the app reveri.com.

01:31:59.760 | So R-E-V-E-R-I.com.

01:32:03.640 | There you can download a zero cost app

01:32:05.960 | for Apple phones or for Android phones.

01:32:10.300 | And there are a variety of different hypnosis scripts.

01:32:12.640 | These are actually self-hypnosis scripts,

01:32:14.240 | and you'll actually hear Dr. David Spiegel talking to you.

01:32:17.140 | He can teach you about hypnosis and how it works.

01:32:19.640 | There are links to scientific studies at that web address

01:32:22.500 | that I gave you before, reveri.com.

01:32:24.900 | You can see the various studies and the various writeups

01:32:27.260 | related to those studies and how this all works.

01:32:29.540 | And they're simple protocols.

01:32:31.280 | You just click on a tab and you listen to the self-hypnosis

01:32:33.740 | and it will take you into hypnosis.

01:32:36.140 | And several of those hypnosis scripts

01:32:38.540 | have been shown clinically to relieve certain patterns

01:32:42.780 | of chronic pain.

01:32:44.200 | So it's a powerful tool.

01:32:45.680 | And I encourage you not to write off the non-drug,

01:32:48.760 | non-supplement tools as less than powerful,

01:32:51.540 | because indeed many people experience

01:32:53.760 | tremendous relief from them.

01:32:55.260 | And of course they also can be combined with drug treatments

01:32:59.020 | if that's right for you or with supplements

01:33:01.640 | and things of that sort to treat pain

01:33:03.180 | if that's right for you.

01:33:04.680 | So again, electro-acupuncture now often supported

01:33:08.840 | by insurance, not always, but often.

01:33:11.200 | Great mechanistic data starting to emerge.

01:33:13.840 | Hypnosis, terrific tool.

01:33:17.280 | There's even the self-hypnosis tool that one can access

01:33:19.940 | through the zero cost app, Reverie,

01:33:21.920 | and lots of great clinical data

01:33:24.920 | and scientific mechanistic data.

01:33:26.640 | There are neuroimaging studies showing

01:33:28.120 | that different brain areas are activated in hypnosis,

01:33:30.520 | so-called default network,

01:33:32.320 | kind of where your brain's kind of idols

01:33:35.180 | and the different circuits that are active at rest

01:33:37.980 | shift with hypnosis and shift long-term

01:33:40.220 | in ways that positively conserve you.

01:33:42.320 | And then these things like laser photobiomodulation,

01:33:45.200 | still more or less in that experimental medical community,

01:33:48.660 | I should say Western medical community, not so certain,

01:33:51.320 | but hopefully there will be data soon.

01:33:53.520 | And hopefully those data will point to mechanisms

01:33:55.920 | that allow the insurance companies

01:33:58.400 | and other sort of medical bodies

01:34:01.360 | to support them if indeed they have a mechanistic basis.

01:34:06.080 | I just want to briefly touch on a common method

01:34:08.560 | of pain relief that speaks to a more general principle

01:34:12.140 | of how things like electroacupuncture

01:34:14.400 | and also some of these new emerging techniques

01:34:17.120 | of kind of like active tissue release

01:34:19.980 | and this principle that you hear a lot about

01:34:21.840 | in sports medicine now,

01:34:22.880 | that when you have pain or injury at one site,

01:34:25.200 | that you should provide pressure above and below that site.

01:34:28.000 | You may have seen this in the Olympics,

01:34:29.940 | which is ongoing now,

01:34:31.760 | where people will put tape on their body

01:34:34.680 | at certain locations.

01:34:35.700 | Oftentimes the logic or what they're saying

01:34:38.900 | is that this is designed to create relief in a joint

01:34:42.120 | or in a limb that's below the tape,

01:34:45.080 | not necessarily under the tape, but above or below.

01:34:48.180 | So for instance, if there's pain in one shoulder,

01:34:50.020 | sometimes they will put it on the trapezius muscle

01:34:53.000 | or things of that sort.

01:34:53.840 | It turns out that there is a basis for this

01:34:56.000 | because of the way that these different nerves run in

01:34:58.700 | from the skin and from the muscles

01:35:01.160 | up into the spinal cord and into the brainstem,

01:35:04.320 | providing pressure on one nerve pathway

01:35:06.360 | can often impact another pathway.

01:35:07.880 | And the simplest and most common example of this

01:35:10.500 | is one that we all do instinctually or intuitively,

01:35:12.980 | even animals do this.

01:35:14.760 | This is something that in the textbooks

01:35:17.240 | is called the GATE theory of pain

01:35:19.000 | developed by Melzack and Wall, kind of classic theory.

01:35:22.320 | Basically we have receptors in our skin,

01:35:25.960 | the so-called C fibers.

01:35:27.200 | That's just a name for these little wires

01:35:29.920 | that come from a particular class of DRGs that's very thin

01:35:33.800 | that brings about certain kinds of nociceptor information.

01:35:37.460 | I want to say pain information, but then the pain people,

01:35:40.380 | believe it or not, they're pain people.

01:35:42.200 | Sometimes they're a pain because what they tell me

01:35:44.460 | is there aren't pain receptors, okay, nociceptors.

01:35:46.880 | That information comes in through the C fibers.

01:35:50.340 | And what happens when we injure something?

01:35:53.920 | Well, provided that we won't damage it worse by touching it,

01:35:57.360 | oftentimes what we will do is we will rub the source of pain

01:36:01.440 | or the location in which we were experiencing pain.

01:36:05.480 | And it turns out that's not an useful thing to do.

01:36:10.480 | When we rub our skin or an area,

01:36:14.380 | or we provide pressure nearby it,

01:36:16.540 | we activate the so-called A fibers,

01:36:18.360 | the bigger wires and neurons that innervate,

01:36:22.120 | meaning they jut into that area of skin.

01:36:24.520 | And those A fibers,

01:36:26.560 | the ones that respond to mechanical pressure

01:36:29.200 | actually are able to inhibit those C fibers,

01:36:32.240 | the ones that are carrying that so-called pain information.

01:36:35.120 | So rubbing an area or providing pressure above

01:36:38.460 | or below an injury actually provides

01:36:40.580 | real pain relief support for the location of that injury

01:36:45.160 | or that pain because of the way that these different

01:36:48.360 | patterns or these different types of neurons interact

01:36:51.560 | with one another.

01:36:52.460 | When I say it inhibits it,

01:36:53.760 | I don't mean that it like shouts at it.

01:36:55.760 | What it does is it releases it's literally kind of like,

01:36:58.520 | vomits up a little bit of a neurotransmitter called GABA.

01:37:02.240 | And GABA is a neurotransmitter that inhibits,

01:37:04.920 | it quiets the activity of other neurons.

01:37:08.200 | And so it's acting as kind of an analgesic, if you will,

01:37:11.860 | it's acting as its own form of drug that you make

01:37:15.640 | with your body to quiet the activity of these pain neurons.

01:37:19.040 | So rubbing a wound provided it doesn't damage the wound

01:37:22.080 | worse or providing pressure above or below,

01:37:25.300 | typically it's above a particular injury,

01:37:28.240 | can have a real effect in relieving some of the pain

01:37:30.720 | of that injury.

01:37:31.560 | And some people have speculated this is through fascia

01:37:34.020 | or this is through other bodily organs and tissues.

01:37:36.960 | And it might be, we're going to do a whole episode on fascia,

01:37:39.320 | it's extremely interesting tissue.

01:37:41.120 | But right now it seems that the main source

01:37:43.100 | of that pain relief is through this A fiber inhibition

01:37:47.400 | of these C fibers, so-called Melzack and Wahl gate theory

01:37:51.480 | of pain, if you'd like to look it up

01:37:52.980 | and learn about that further.

01:37:55.120 | Now let's talk about a phenomenon that has long intrigued

01:37:58.640 | and perplexed people for probably thousands of years,

01:38:02.600 | and that's redheads.

01:38:05.160 | You may have heard before that redheads have a higher pain

01:38:07.720 | threshold than other individuals.

01:38:10.040 | And indeed that is true.

01:38:11.840 | There's now a study that looked at this mechanistically.

01:38:16.060 | There's a gene called the MC1R gene,

01:38:20.580 | and this MC1R gene encodes

01:38:22.960 | for a number of different proteins.

01:38:25.440 | Some of those proteins, of course,

01:38:27.060 | are related to the production of melanin.

01:38:29.320 | This is why redheads often, not always,

01:38:31.640 | but often are very fair skinned,

01:38:33.720 | sometimes have freckles, not always,

01:38:35.820 | and of course have red hair.

01:38:37.480 | Some people are really intense gingers,

01:38:40.060 | not psychologically or emotionally intense,

01:38:42.620 | perhaps that too, but meaning their hair is very,

01:38:45.460 | very red, others it's a lighter red.

01:38:47.440 | So of course there's variation here, but this gene,

01:38:50.560 | this MC1R gene is associated with a pathway that relates

01:38:55.560 | to something that I've talked about on this podcast before

01:38:58.840 | during the episode on hunger and feeding.

01:39:01.640 | And this is POMC, POMC stands for pro-opiomelanocortin,

01:39:06.640 | and POMC is cut up, it's cleaved into different hormones,

01:39:13.360 | including one that enhances pain perception.

01:39:16.680 | This is melanocyte stimulating hormone.

01:39:19.340 | And another one that blocks pain, beta endorphin.

01:39:23.120 | Now, if you listen to the episodes on testosterone

01:39:25.720 | and estrogen and the episodes on hunger and feeding,

01:39:29.280 | some of these molecules will start to ring a bell.

01:39:32.180 | Things like melanostimulating hormone relate

01:39:34.480 | to pigmentation in the skin,

01:39:35.940 | relate to sexual arousal, et cetera.

01:39:38.200 | But it turns out that in redheads,

01:39:40.900 | the because of the fact that they have this gene,

01:39:43.460 | this MC1R gene, the POMC, pro-opiomelanocortin,

01:39:48.460 | that's cut into different hormones,

01:39:51.260 | melanocyte stimulating hormone,

01:39:52.900 | and another one, beta endorphin.

01:39:56.000 | Beta endorphin should cue you to the fact

01:39:59.380 | that this is in the pain pathway.

01:40:00.980 | The endorphins are endogenously made,

01:40:03.620 | meaning made within our body opioids.

01:40:06.500 | They actually make us feel numb

01:40:09.880 | in response to certain kinds of pain.

01:40:11.420 | Now, not completely numb,

01:40:12.780 | but they numb or reduce our perception of pain

01:40:16.960 | because of the ways in which they are released

01:40:19.420 | from certain brain centers.

01:40:20.820 | We'll talk about those brain centers in a moment.

01:40:23.300 | So what's really interesting is that this study showed

01:40:27.460 | that the presence of these hormones is in everybody.

01:40:31.500 | We all have melanocortin-4, we all have beta endorphins,

01:40:35.380 | we all have POMC, et cetera.

01:40:37.560 | But redheads make more of these endogenous endorphins.

01:40:41.700 | And that's interesting.

01:40:42.780 | It allows them to buffer against the pain response.

01:40:46.140 | I have a personal anecdote to share with you

01:40:47.940 | about this redhead and heightened levels

01:40:50.860 | of pain tolerance phenomenon.

01:40:52.860 | Obviously, I'm not a redhead, I don't dye my hair,

01:40:55.940 | but my partner for many years was a redhead

01:40:59.260 | and still is a redhead.

01:41:00.540 | She had bright red hair and had that since childhood.

01:41:05.060 | Well, we had the fortunate experience of becoming friends

01:41:08.740 | with Wim Hof and family.

01:41:10.880 | They actually came out to visit us

01:41:12.500 | and did a series of seminars in the Bay Area.

01:41:15.500 | This was in 2016, as I recall.

01:41:18.400 | And my partner, she had never done an ice bath.

01:41:22.740 | She had never done any kind of real cold water

01:41:25.400 | exposure experience before,

01:41:27.100 | but it is one particular gathering,

01:41:28.680 | as is often the case when Wim is around,

01:41:30.540 | there was an ice bath and a number of people

01:41:32.080 | were getting into this thing.

01:41:32.980 | This was actually before a dinner event.

01:41:34.900 | And I think for most people who have never done an ice bath

01:41:38.020 | getting in for 30 seconds or a minute is tolerable,

01:41:41.860 | but it takes some effort,

01:41:43.220 | it takes some willpower and takes some overcoming

01:41:45.420 | that pain barrier 'cause it is a little bit painful,

01:41:47.780 | not a lot.

01:41:48.620 | Some people can stay in longer, three minutes,

01:41:51.980 | five minutes without much discomfort.

01:41:54.740 | What was incredible is that without any desire

01:41:57.680 | to compete with anybody else, my partner, redhead,

01:42:01.220 | got into the ice bath and just like sat there for 10 minutes.

01:42:04.580 | In fact, at one point, she just kind of turned to me

01:42:06.260 | and said, "I don't really feel pain.

01:42:10.780 | I'm not really in pain."

01:42:12.100 | And Wim loved this.

01:42:13.220 | Wim thought it was great.

01:42:14.140 | He thought it was like the most terrific thing in the world.

01:42:15.900 | And he got back in the ice bath and they became fast friends

01:42:18.220 | and I think they're probably still fast friends.

01:42:20.820 | So in any event, that's an N of one,

01:42:23.280 | what we call an anecdotal example.

01:42:25.860 | Anecdotal is not really a term that we should use too much

01:42:28.220 | 'cause it's N of one anecdotes are just that,

01:42:31.380 | they're just anecdotes.

01:42:32.720 | But it's been described many times in various clinics

01:42:36.840 | that were by anesthesiologists,

01:42:38.840 | by observation of coaches, et cetera,

01:42:41.320 | that redheads, men and women who are redheads,

01:42:45.140 | seem to have this higher pain threshold.

01:42:47.140 | And it does seem to be because their body

01:42:49.220 | naturally produces ways to counter the pain response.

01:42:53.920 | They produce their own endogenous opioids.

01:42:56.760 | Now this of course should not be taken to mean

01:42:59.120 | that redheads can tolerate more pain

01:43:01.620 | and therefore should be subjected to more pain.

01:43:03.940 | All it means is that their threshold for pain on average,

01:43:07.780 | not all of them, but on average is shifted higher

01:43:11.040 | than that of other individuals.

01:43:12.960 | And it remains to be determined whether or not

01:43:15.760 | other light-skinned, light-haired individuals

01:43:18.460 | also have a heightened level of pain threshold.

01:43:20.980 | And I should mention because I mentioned the ice bath

01:43:23.440 | that of course pain threshold is something

01:43:26.160 | that can be built up and provide you to do that safely

01:43:28.920 | in ways that aren't damaging your tissues

01:43:31.100 | because of course pain is a signal that is designed

01:43:33.560 | to help you to keep from harming yourself.

01:43:36.280 | But provided that you can do that in a way that's safe

01:43:38.580 | and doesn't damage your tissues,

01:43:41.120 | increasing your pain threshold through the use of things

01:43:43.320 | like ice baths is something that really can be done.

01:43:45.960 | It has a lot to do with these contextual

01:43:48.380 | or top-down modulations of the experience.

01:43:51.360 | You can tell yourself that this is good for me

01:43:55.040 | or I'm doing this by choice or whatever it is,

01:43:57.360 | you could distract yourself.

01:43:58.440 | There are a huge number of different ways

01:43:59.920 | that one could do that.

01:44:01.140 | One of the more interesting ways

01:44:03.200 | for which there are actually really good scientific data

01:44:06.040 | come from my colleague, Sean Mackey's lab.

01:44:08.800 | And that actually looked at how love

01:44:12.040 | and in particular the experience of obsessive love

01:44:16.000 | could actually counter the pain response,

01:44:18.640 | not just in redheads, but in everybody.

01:44:21.400 | So that study I'll just briefly describe.

01:44:24.640 | It involved having people come into the laboratory

01:44:26.640 | and experience any one or a number

01:44:28.740 | of different painful stimuli,

01:44:30.580 | but they had selectively recruited subjects

01:44:33.380 | that were in new relationships

01:44:35.220 | for which there was a high degree of infatuation.

01:44:38.080 | So much so that the people couldn't stop thinking about

01:44:40.680 | or communicating with that new partner

01:44:43.640 | up to 80% of their waking time, which is a lot.

01:44:47.240 | That constant obsessing about that partner

01:44:51.560 | was correlated with, it wasn't causal necessarily,

01:44:54.160 | but was correlated with the ability

01:44:57.020 | to sustain higher levels of pain

01:44:59.400 | than people who were in more typical

01:45:02.720 | non-obsessive forms of love,

01:45:05.820 | longstanding relationships

01:45:07.400 | where there wasn't long obsessive love rather.

01:45:10.480 | And of course, in this study,

01:45:12.040 | there were a lot of good control groups.

01:45:13.960 | They included a distractor.

01:45:15.960 | They included people obsessing about other things,

01:45:18.780 | their pet, et cetera.

01:45:19.720 | They included other forms of love and attachment,

01:45:23.720 | but it does seem that certain patterns of thinking

01:45:26.380 | can allow us to buffer ourselves against the pain response.

01:45:30.020 | And that should not be surprising.

01:45:32.520 | Certain forms of thinking are associated

01:45:34.520 | with the release of particular neuromodulators,

01:45:36.800 | in particular dopamine.

01:45:38.480 | And dopamine, it may seem is kind of the thing

01:45:42.240 | that underlies everything, but it's not.

01:45:44.160 | Dopamine is a molecule that's associated

01:45:46.800 | with novelty, expectation, motivation, and reward.

01:45:49.740 | We talked about this at the beginning of the episode,

01:45:52.200 | that it's really the molecule of expectation

01:45:55.280 | and motivation and hope and excitement

01:45:58.440 | more than it's associated with the receival of the reward.

01:46:02.100 | Well, dopamine is coursing throughout the brain

01:46:05.840 | at heightened levels and coursing throughout the body

01:46:08.200 | at heightened levels when we fall in love.

01:46:11.160 | This probably has some adaptive mechanism

01:46:13.580 | that ensured pair bonding between people or who knows,

01:46:17.080 | maybe it ensured not bonding to multiple people.

01:46:19.280 | Nobody really knows how dopamine functions

01:46:22.400 | in terms of pair bonding,

01:46:24.800 | but it is known that when people fall in love,

01:46:28.100 | new relationships create very high levels of dopamine.

01:46:31.600 | And that's probably the mechanistic basis

01:46:34.440 | by which these people were able to buffer the pain response

01:46:37.600 | by thinking about their partner

01:46:40.160 | or this new relationship that they're in

01:46:41.920 | almost obsessively or obsessively.

01:46:44.600 | Now that raises a deeper question.

01:46:46.440 | We should always be asking, yeah, but how, how?

01:46:48.680 | Well, the dopamine system can have powerful effects

01:46:52.840 | on the inflammation system.

01:46:54.760 | And it doesn't do this through mysterious ways.

01:46:57.060 | It does this by interacting through the brainstem

01:47:00.240 | and some of the neurons that innervate the spleen

01:47:03.120 | and other areas of the body that deploy cells

01:47:07.280 | to go combat infection, inflammation, and pain.

01:47:11.280 | And the ways in which dopamine can modulate pain,

01:47:14.120 | and in this case, this particular study,

01:47:16.720 | transform our experience of pain,

01:47:18.440 | maybe even into something that's pleasureful,

01:47:21.240 | is not mysterious.

01:47:22.640 | It's really through the activation of brainstem neurons

01:47:25.960 | that communicate with areas of our body

01:47:28.780 | that deploy things like immune cells.

01:47:31.520 | So for instance, we have neurons in our brainstem

01:47:34.780 | that can be modulated by the release of dopamine.

01:47:38.400 | And those neurons in the brainstem

01:47:40.240 | control the release of immune cells

01:47:42.540 | from tissues like the spleen or organs like the spleen.

01:47:45.920 | And those immune cells can then go combat infection.

01:47:48.800 | We've heard before that when we're happy,

01:47:50.460 | we're better able to combat infection, deal with pain,

01:47:53.600 | deal with all sorts of things,

01:47:55.120 | it essentially makes us more resilient.

01:47:57.160 | And that's not because dopamine is some magic molecule.

01:47:59.760 | It's because dopamine affects particular circuits

01:48:02.460 | and tells in a very neurobiological way,

01:48:05.560 | in a biochemical way,

01:48:06.800 | tells those cells and circuits that conditions are good.

01:48:10.140 | Despite the fact that there's pain in the body,

01:48:12.040 | conditions are good.

01:48:12.960 | You're in love or conditions are good.

01:48:14.480 | You want to be in this experience or conditions are good.

01:48:17.560 | This is for a greater cause that you're fighting

01:48:20.060 | or suffering for some larger purpose.

01:48:22.540 | So all of that has existed largely in the realm of psychology

01:48:25.560 | and even motivational literature and this kind of thing,

01:48:28.140 | but there's a real mechanistic basis for it.

01:48:30.080 | Dopamine is a molecule that can bind to receptor sites

01:48:32.740 | on these brain areas.

01:48:34.020 | Those brain areas can then modulate the organs

01:48:36.140 | and tissues of the body

01:48:37.560 | that can allow us to lean into challenge.

01:48:39.980 | And those challenges can be infection.

01:48:41.580 | It can be physical pain.

01:48:43.120 | It can be long bouts of effort that are required of us.

01:48:47.060 | And I think many people have described the feeling

01:48:50.240 | of being newly in love as a heightened level of energy,

01:48:53.340 | a capacity to do anything.

01:48:54.640 | I mean, the whole concept of a muse

01:48:57.160 | is one in which some individual or some thing,

01:49:00.180 | either imagined or real, enters our life

01:49:03.060 | and we can use that as fuel.

01:49:06.640 | And that fuel is chemical fuel

01:49:08.900 | and that chemical fuel is dopamine.

01:49:10.820 | And it really does allow for more resilience

01:49:12.760 | and can even transform the experience of pain

01:49:15.740 | or what would otherwise be pain

01:49:17.500 | into an experience of pleasure.

01:49:19.460 | So along those lines, let's talk about pleasure.

01:49:22.220 | With all the cells and tissues and machinery

01:49:24.520 | related to pain,

01:49:26.100 | you might think that our entire touch system

01:49:28.540 | is designed to allow us to detect pain

01:49:31.340 | and to avoid tissue damage.

01:49:32.660 | And while a good percentage of it is devoted to that,

01:49:36.420 | a good percentage of it is also devoted

01:49:38.440 | to this thing that we call pleasure.

01:49:40.900 | And that should come as no surprise.

01:49:43.300 | Pleasure isn't just there for our pleasure.

01:49:46.460 | It serves an adaptive role.

01:49:48.460 | And that adaptive role relates to the fact

01:49:50.480 | that every species has a primary goal,

01:49:52.860 | which is to make more of itself.

01:49:54.820 | Otherwise it would go extinct.

01:49:56.900 | That process of making more of itself, sexual reproduction,

01:50:01.580 | is closely associated with the sensation

01:50:04.340 | and the perception of pleasure.

01:50:06.060 | And it's no surprise that not only is the highest density

01:50:10.380 | of sensory receptors in and on and around the genitalia,

01:50:15.220 | but the process of reproduction evokes sensations

01:50:19.100 | and molecules and perceptions associated with pleasure.

01:50:22.460 | And the currency of pleasure

01:50:24.860 | exists in multiple chemical systems,

01:50:27.160 | but the primary ones are the dopamine system,

01:50:29.940 | which is the anticipation of pleasure

01:50:31.780 | and the work required to achieve the ability

01:50:37.700 | to experience that pleasure

01:50:39.520 | and the serotonin system,

01:50:41.580 | which is more closely related

01:50:43.080 | to the immediate experience of that pleasure.

01:50:45.560 | And from dopamine and serotonin stem out other hormones

01:50:49.520 | and molecules, things like oxytocin,

01:50:52.180 | which are associated with pair bonding.

01:50:53.800 | Oxytocin is more closely associated

01:50:55.980 | with the serotonin system,

01:50:57.580 | biochemically and at the circuit level,

01:51:00.180 | meaning the areas of the brain and body

01:51:01.880 | that manufacture a lot of serotonin, usually, not always,

01:51:05.160 | but usually contain neurons that also manufacture

01:51:07.900 | and make use of the molecule oxytocin.

01:51:10.400 | Those chemicals together create sensations of warmth,

01:51:15.460 | of wellbeing, of safety.

01:51:18.520 | The dopamine molecule is more closely associated

01:51:21.800 | with hormones like testosterone

01:51:24.200 | and other molecules involved with pursuit

01:51:26.960 | and further effort in order to get more of whatever

01:51:30.500 | could potentially cause more release of dopamine.

01:51:33.340 | So this is a very broad strokes, no pun intended,

01:51:36.840 | description of the pleasure system.

01:51:39.680 | There are, of course, other molecules as well.

01:51:41.680 | One in particular that's very interesting

01:51:44.400 | is something called PEA.

01:51:46.600 | PEA stands for phenylethylamine,

01:51:49.880 | sometimes also referred to as phenylethylamine,

01:51:53.000 | depending on who you are and where you live.

01:51:56.120 | How you pronounce it doesn't really matter.

01:51:59.040 | PEA is a molecule which is incredibly potent

01:52:03.760 | at augmenting or increasing the activity of certain cells

01:52:08.080 | and neural circuits that relate to the pleasure system.

01:52:11.560 | PEA has purportedly been thought to be released

01:52:16.120 | in response to ingestion of things

01:52:17.720 | like certain forms of dark chocolate.

01:52:19.800 | Some people take it in supplement form.

01:52:21.760 | It's a bit of a stimulant,

01:52:24.040 | but it also seems to heighten the perception of pleasure

01:52:27.540 | in response to a particular amount

01:52:29.460 | of dopamine and/or serotonin.

01:52:31.440 | So for instance, in a kind of a arbitrary experiment

01:52:34.440 | and units type example,

01:52:36.200 | if a given experience evokes a particular amount

01:52:39.680 | of serotonin and dopamine and gives rise

01:52:42.220 | to a subjective experience of pleasure

01:52:44.120 | of say level three out of 10,

01:52:46.200 | the ingestion of PEA prior to that experience

01:52:48.680 | can increase the rating of that experience

01:52:51.880 | as more pleasureful, maybe a four or a five or even a six.

01:52:55.620 | And PEA is known to be present in,

01:52:59.480 | or I should say its release is stimulated

01:53:02.000 | by a number of different compounds such as dark chocolate,

01:53:06.080 | certain things like aspartame

01:53:07.840 | and certain people can actually increase

01:53:09.920 | the amount of PEA released.

01:53:11.540 | Some of these glutamate related molecules like aspartame

01:53:15.340 | or things that are in the glutamate pathway

01:53:17.080 | can increase PEA release.

01:53:18.700 | And then some people will actually take PEA

01:53:20.840 | in supplement form for its mild stimulant properties

01:53:25.280 | as well as for increasing the perception of

01:53:28.960 | or the ability to experience pleasure.

01:53:31.540 | It's not a sledgehammer, it's not a like dopamine itself.

01:53:35.960 | People that take things like macuna purines,

01:53:38.120 | L-DOPA or drugs of abuse,

01:53:40.460 | which I certainly don't recommend,

01:53:41.800 | things like cocaine or amphetamine

01:53:44.720 | experience tremendous increases in dopamine,

01:53:47.900 | not so much increases in serotonin.

01:53:50.520 | Some people will take serotonin in precursor form

01:53:55.160 | like 5-HTP or serotonin itself,

01:53:57.540 | or they'll take the amino acid precursor like tryptophan.

01:54:00.400 | I'm not saying these things as recommendations

01:54:02.380 | for increasingly one sense of pleasure.

01:54:04.460 | I'm describing them because of what they do

01:54:07.280 | generally falls into two categories.

01:54:09.960 | The first category is to raise the foundation,

01:54:13.700 | what we call the tonic level of dopamine and serotonin.

01:54:17.360 | So if levels of serotonin and dopamine are too low,

01:54:22.360 | it becomes almost impossible to experience pleasure.

01:54:27.480 | There's a so-called ahedonia.

01:54:29.760 | This is also described as depression,

01:54:31.820 | although it needn't be long-term depression.

01:54:34.660 | So certain drugs like antidepressants,

01:54:37.460 | like Wellbutrin, Bupriarone as it's commonly called,

01:54:42.180 | or the so-called SSRIs,

01:54:44.280 | the serotonin selective reuptake inhibitors, excuse me,

01:54:47.980 | like Prozac, Zoloft and similar

01:54:50.000 | will increase dopamine and serotonin respectively.

01:54:53.260 | They're not increasing the peaks in those molecules.

01:54:56.920 | What we call the acute release of those molecules,

01:55:00.160 | what they're doing is they're raising the overall levels

01:55:02.720 | of those molecules.

01:55:03.560 | They're raising the sort of foundation or the tide,

01:55:06.500 | if you will, think about it as your mood

01:55:08.740 | or your pleasure rather is like a boat.

01:55:11.040 | And if it's on the shore and it can't get out to sea

01:55:13.760 | unless that tide is high enough,

01:55:15.160 | that's kind of the way to think about these tonic levels

01:55:17.440 | of dopamine and serotonin.

01:55:19.000 | Now, most of us fortunately do not have problems

01:55:22.500 | with our baseline or our tonic levels

01:55:25.160 | of dopamine and serotonin release.

01:55:27.360 | Things like PEA in that case

01:55:29.240 | will cause a slight increase in that tide

01:55:31.860 | and make the ability of certain experiences

01:55:36.560 | to increase dopamine further more available.

01:55:40.200 | What we call this in neuroscience is so-called gain control.

01:55:44.080 | It can kind of turn up the volume,

01:55:46.120 | bring us closer to the threshold

01:55:47.960 | to activate certain circuits.

01:55:49.560 | And this is really what we mean

01:55:51.140 | when we say a neuromodulator, okay?

01:55:54.360 | This is why when you are very happy about something,

01:55:57.840 | let's say you're out with your friends,

01:55:59.320 | you're really excited, you know,

01:56:01.000 | maybe depending on where you live

01:56:02.600 | and what's going on in your area of the world right now,

01:56:04.500 | like, you know, like I have a niece

01:56:06.320 | and she's been locked up in quarantine

01:56:07.920 | for a long time recently because it was deemed safe.

01:56:10.220 | She got to go to summer camp.

01:56:11.580 | I have never seen that kid so happy to spend,

01:56:14.920 | excuse me, spend time with her friends.

01:56:16.880 | She was so excited and it was really amazing

01:56:20.560 | to see how excited she was.

01:56:21.640 | Her baseline levels of dopamine were clearly up.

01:56:24.680 | So much so that when she saw her friends,

01:56:28.200 | she literally started squealing, okay?

01:56:30.560 | They were squealing, she was squealing.

01:56:31.920 | Everyone was squealing.

01:56:32.760 | I wasn't squealing.

01:56:33.760 | I would admit it if I was squealing.

01:56:35.160 | I wasn't squealing, but it was such a delight to see.

01:56:37.800 | And I'm sure that made my dopamine levels go up,

01:56:39.860 | which was, she was just so excited,

01:56:41.720 | such that anything and everything

01:56:43.560 | felt like an exciting stimulus.

01:56:45.000 | This is pleasure, right?

01:56:46.800 | And I don't want to write off the experience

01:56:48.600 | from a neurobiological reductionist standpoint,

01:56:51.600 | quite the opposite.

01:56:52.440 | It's really beautiful to see, again,

01:56:54.400 | this principle that different experiences

01:56:57.800 | and the experience of pleasure from different things,

01:57:01.020 | seeing your friends for the first time,

01:57:02.420 | summer camp for a kid, whatever it might happen to be,

01:57:06.200 | use the same currency, dopamine,

01:57:08.780 | use the same currency, serotonin.

01:57:11.400 | And this is a principle that I hope

01:57:13.000 | in listening to this podcast

01:57:14.360 | and even some of its repetitive features

01:57:16.140 | from one episode to the next,

01:57:18.680 | I'm hoping that those will start to embed in your mind

01:57:20.780 | that the brain and body use these common currencies

01:57:24.100 | for different experiences.

01:57:25.540 | So yes, if your dopamine and serotonin,

01:57:27.740 | or I should say if your dopamine

01:57:29.700 | and/or serotonin levels are too low,

01:57:32.780 | it will be very hard to achieve pleasure,

01:57:34.820 | to experience physical pleasure

01:57:36.440 | or emotional pleasure of any kind.

01:57:38.660 | That's why treatments of the sort

01:57:40.700 | that I described a minute ago might be right for you.

01:57:43.740 | Obviously, we can't determine if they're right for you.

01:57:45.500 | It's also why they have side effects.

01:57:47.140 | If you artificially increase these molecules

01:57:49.900 | that are associated with pleasure,

01:57:51.620 | oftentimes you get a lack of motivation

01:57:53.940 | to go seek things like food.

01:57:55.360 | People don't get much interest in food

01:57:57.160 | 'cause why should they

01:57:58.100 | if their serotonin levels are already up?

01:58:00.260 | Again, there's a ton of individual variation.

01:58:02.820 | I don't want to say that these antidepressants

01:58:05.100 | are always bad.

01:58:06.340 | Sometimes they've saved lives.

01:58:08.300 | They've saved millions of lives.

01:58:09.640 | Sometimes people have side effects

01:58:10.920 | that make them not the right choice.

01:58:12.520 | So it has to be determined for the individual.

01:58:15.820 | Things like PEA are a more subtle effect.

01:58:18.640 | I should mention PEA supplementation

01:58:21.120 | is something that a number of people use,

01:58:23.180 | but it's very short-lived.

01:58:24.580 | Because of the half-life of this molecule is very brief,

01:58:27.760 | the effect only lasts about 20 minutes or so.

01:58:30.560 | Things like L-DOPA,

01:58:33.220 | macunipurines lead to longer baseline increases in dopamine.

01:58:38.220 | But remember, anytime you raise a baseline,

01:58:42.100 | you reduce the so-called signal to noise.

01:58:46.180 | What it means is if you're riding around

01:58:48.080 | at really high dopamine,

01:58:49.460 | at first, everything will start to seem exciting.

01:58:51.780 | Like my niece and seeing her friends for the first time,

01:58:53.740 | everything's exciting.

01:58:55.220 | But then what will happen

01:58:56.260 | is when your dopamine levels return to more normal levels,

01:58:59.620 | it will take a much greater dopamine increase,

01:59:02.780 | a much bigger event, more novel, more exciting

01:59:06.020 | in order to achieve the sense

01:59:08.540 | that what you're experiencing is pleasureful.

01:59:11.380 | And this is because of the relationship

01:59:13.380 | between pleasure and pain.

01:59:15.420 | Now, in a future episode,

01:59:16.580 | we are going to go deep into this relationship

01:59:18.540 | between pleasure and pain.

01:59:20.340 | But just briefly, as a precursor to that,

01:59:23.240 | and because it's relevant

01:59:24.380 | to the conversation that we've been having,

01:59:26.580 | you might want to be wary of any experience,

01:59:31.700 | any experience, no matter how it arrives,

01:59:34.720 | chemical, physical, emotional, or some combination.

01:59:38.480 | You might want to be wary

01:59:39.860 | of letting your dopamine go too high,

01:59:42.060 | and certainly you want to be wary of it going too low

01:59:44.220 | because of the way that these circuits adjust.

01:59:46.540 | Basically, every time that the pleasure system

01:59:48.940 | is kicked in in high gear,

01:59:51.820 | an absolutely spectacular event,

01:59:54.180 | you cannot be more ecstatic.

01:59:56.860 | There is a mirror symmetric activation of the pain system.

02:00:01.860 | And this might seem like an evil curse of biology,

02:00:05.740 | but it's not.

02:00:06.580 | This is actually a way to protect this whole system

02:00:09.760 | of reward and motivation that I talked about

02:00:11.900 | at the beginning of the episode.

02:00:14.140 | It might sound great to just ingest substances

02:00:16.380 | or engage in behaviors where it's just dopamine,

02:00:18.340 | dopamine, dopamine, and just constantly be motivated,

02:00:21.440 | but the system will eventually crash.

02:00:23.980 | And so what happens is

02:00:24.840 | when you have a big increase in dopamine,

02:00:26.900 | you also will get a big increase in the circuits

02:00:29.940 | that underlie our sense of disappointment

02:00:32.940 | and readjusting the balance.

02:00:34.940 | And with repeated exposure to high levels of dopamine,

02:00:38.020 | not naturally occurring wonderful events,

02:00:40.720 | but really high chemically induced peaks in dopamine,

02:00:45.720 | high magnitude chemically induced peaks in dopamine,

02:00:49.220 | what happens is those peaks in dopamine

02:00:51.300 | start to go down and down and down

02:00:53.600 | in response to the same,

02:00:55.280 | what ought to be incredible experience.

02:00:57.780 | We start to what's called habituate or attenuate,

02:01:01.380 | and yet the pain increases in size.

02:01:05.800 | And this has a preservative function

02:01:08.340 | in keeping us safe, believe it or not.

02:01:11.000 | But what I just described is actually the basis

02:01:13.340 | of most, if not all forms of addiction,

02:01:16.100 | something that we will deal with

02:01:17.360 | in a future episode in depth.

02:01:19.360 | So what should you think about all this?

02:01:20.820 | How should you think about pleasure

02:01:21.920 | and how should you think about pain?

02:01:23.360 | What is too much pleasure?

02:01:25.240 | Well, that's going to differ from person to person,

02:01:28.840 | but to the extent that one can access pleasure repeatedly

02:01:33.380 | over time, ideally without chemical augmentation,

02:01:37.640 | certainly not excessive chemical augmentation,

02:01:40.020 | that means that this pleasure system is tuned up well

02:01:42.660 | and can continue to experience pleasure.

02:01:44.460 | However, if you find yourself engaging

02:01:47.540 | in the same behavior over and over again,

02:01:50.080 | but achieving less and less pleasure from it,

02:01:52.880 | chances are you want to adjust down

02:01:56.320 | how often you engage in that behavior

02:02:00.180 | and or adjust down your expectation of reward

02:02:04.400 | every time you engage in that behavior.

02:02:06.580 | What do I mean by that?

02:02:08.920 | Well, at the beginning of the episode,

02:02:10.320 | I talked about how dopamine will allow us

02:02:13.760 | to get into bouts of hard work.

02:02:15.780 | We will work very hard to pursue a reward

02:02:19.020 | and that's really what dopamine does.

02:02:20.400 | And then when the reward comes,

02:02:21.820 | that doesn't increase our dopamine.

02:02:24.040 | In fact, our dopamine levels go down.

02:02:28.080 | One of the key things that we can all do

02:02:30.580 | to adjust our ability to experience pleasure

02:02:34.260 | is to engage in that intermittent reward schedule.

02:02:38.840 | You can either adjust down the peak in dopamine,

02:02:41.580 | meaning not let yourself ever get too happy,

02:02:43.440 | but that's no fun, right?

02:02:44.540 | Life is about occasionally achieving or experiencing ecstasy

02:02:49.540 | but every once in a while, remove the reward.

02:02:52.820 | And of course I don't mean ecstasy the drug,

02:02:54.300 | that's a separate matter.

02:02:55.180 | The MDMA trials are a separate matter, very interesting.

02:02:57.600 | I want to be clear, I meant psychological

02:02:59.660 | and physical ecstasy of the natural sort.

02:03:03.180 | I immense interest in what's going on in the MDMA trials,

02:03:06.920 | but just for clarity purposes,

02:03:09.340 | that's a separate topic that we will cover

02:03:11.420 | in an episode, excuse me, very soon.

02:03:14.340 | So how do you adjust this dopamine system?

02:03:17.260 | Well, every once in a while at random,

02:03:20.020 | not in a predictable way, you remove the reward

02:03:24.980 | and that will keep you and your dopamine system

02:03:27.760 | tuned up in the proper ways.

02:03:30.040 | The gain of the dopamine system, as we say,

02:03:32.600 | will be adjusted so that you can continue

02:03:34.900 | to experience dopamine and serotonin

02:03:37.220 | when you actually get the reward.

02:03:38.820 | This can be translated into a huge number

02:03:42.860 | of different domains, but I want to give some examples

02:03:45.240 | because I'm sure that many of you are asking,

02:03:47.280 | wait, what does this actually mean?

02:03:48.460 | Okay, let's say you're a student

02:03:50.200 | or this could be a student in academia

02:03:52.840 | or this could be a student of a physical practice.

02:03:56.180 | Every once in a while, when you do something really well,

02:03:59.100 | maybe that's even just showing up to the practice.

02:04:02.540 | Rather than pat yourself on the back, just tell yourself,

02:04:06.020 | yeah, that's the minimum that's expected of me.

02:04:08.120 | When everyone's excited about something that you're doing,

02:04:10.580 | maybe you're excited about it,

02:04:12.080 | try and adjust down your excitement a little bit.

02:04:14.820 | I know this might seem counterintuitive,

02:04:16.860 | but you're preserving the ability to experience excitement

02:04:20.140 | in a variety of contexts.

02:04:21.940 | Let's say you get a big monetary award.

02:04:25.500 | Well, that's great, I'm happy for you and that's wonderful.

02:04:30.300 | However, you should be a little bit wary

02:04:33.100 | if you care about your dopamine system

02:04:34.760 | and you care about your ability

02:04:35.880 | to get subsequent monetary rewards, excuse me,

02:04:39.700 | awards, rewards, doesn't matter which, through effort.

02:04:42.540 | If you want to be able to maintain the ability

02:04:44.540 | to exert effort, well, then you probably wouldn't want

02:04:47.300 | to run out and immediately buy something

02:04:49.460 | with that monetary reward.

02:04:51.160 | In other words, you wouldn't want to layer on

02:04:52.620 | more dopamine release, okay?

02:04:55.520 | You might, but you might not, you might skip it.

02:04:59.440 | What you'll find then is that your motivation

02:05:01.500 | is essentially infinite.

02:05:03.060 | This is what I described at the beginning of the episode.

02:05:05.480 | And again, it's because dopamine is this currency.

02:05:08.660 | It's like a, these days you hear a lot about Bitcoin

02:05:11.200 | and Ethereum and Dogecoin and US dollars and euros

02:05:15.140 | and all this other stuff.

02:05:16.700 | But the currency that you use in your body

02:05:20.740 | doesn't matter what external currency those are.

02:05:23.140 | In fact, as you watch the value of different currencies

02:05:25.740 | go up, whether or not it's cryptocurrency

02:05:27.300 | or standard currency, the value is actually reflective

02:05:30.880 | of the dopamine that exists inside of people, right?

02:05:33.800 | So all the excitement about a particular currency,

02:05:36.400 | crypto or otherwise, is really just dopamine.

02:05:39.620 | That's the currency that we all use.

02:05:42.900 | And there's no negotiating that.

02:05:44.680 | That's just the way that we're built.

02:05:46.760 | Now, to give yet other examples,

02:05:48.780 | let's say you're teaching other people how to do something

02:05:51.100 | and they do something exceptionally well.

02:05:53.340 | If you reward them every single time,

02:05:55.740 | and in particular, if you reward them with something

02:05:57.980 | that's even greater than the experience of what they did,

02:06:00.900 | so let's say kids win a soccer game and they're ecstatic,

02:06:04.100 | they're jumping all over the place, they're super excited,

02:06:06.460 | and you reward them with an even bigger experience,

02:06:09.620 | a celebration, you are actually inhibiting their ability

02:06:14.520 | to perform the same set of activities

02:06:17.640 | that led them to the win if,

02:06:19.820 | and I really want to underscore,

02:06:21.040 | if you reward them every time.

02:06:22.940 | Of course, we should reward kids and each other

02:06:26.260 | and ourselves for our accomplishments,

02:06:28.380 | but you don't want to do it every time.

02:06:30.780 | And sure, there will be some disappointment

02:06:32.980 | from suddenly removing the reward that you expected,

02:06:37.840 | but that's exactly the point.

02:06:39.180 | That's what keeps these circuits tuned up properly.

02:06:41.820 | Now there's the other form of pleasure,

02:06:43.300 | which is the more immediate visceral or sensory experience

02:06:48.300 | of pleasure.

02:06:49.560 | This is distinct from goals and goal-directed behavior.

02:06:51.720 | I'm talking about the immediate experience.

02:06:53.320 | This is more of the serotonergic system.

02:06:55.800 | There are other systems involved too,

02:06:57.560 | but this is also the system that draws out

02:07:00.840 | those endogenous opioids from a particular structure.

02:07:04.120 | We have a structure in the back of our brain called PAG,

02:07:06.520 | P-A-G, it's the periaqueductal gray area.

02:07:10.000 | Very interesting brain area that is associated

02:07:12.800 | with pain, but also with pleasure,

02:07:14.300 | because under certain conditions,

02:07:16.460 | it deploys endogenous opioids

02:07:19.340 | and gives us a kind of blissed out feeling, okay?

02:07:22.260 | This is not like the opioids of the opioid epidemic sort

02:07:25.580 | that people take, and unfortunately have led

02:07:28.000 | to tremendous amounts of suffering and abuse.

02:07:30.440 | These are endogenously released opioids.

02:07:32.960 | These are the kind of opioids that come out

02:07:34.400 | from long distance bouts of physical exercise and running.

02:07:38.060 | These are the opioids that are deployed

02:07:40.140 | in response to giving birth and overcoming

02:07:42.940 | the tremendous pain of childbirth.

02:07:45.800 | So PAG is very contextual,

02:07:48.360 | and there are a few types of stimuli,

02:07:51.200 | or I should say events in life.

02:07:53.800 | I'm really showing my nerdy side.

02:07:55.280 | There are a few types of stimuli,

02:07:56.740 | I'm talking about experiences,

02:07:58.240 | that evoke endogenous opioid release from PAG.

02:08:02.280 | One is sexual activity.

02:08:05.020 | Sexual activity can increase pain threshold,

02:08:08.380 | and here I am not suggesting or getting involved

02:08:12.820 | in anyone's particular proclivities or personal experiences.

02:08:15.520 | You're welcome to editorialize this however you like.

02:08:18.020 | However, what I'm talking about are animal data,

02:08:21.180 | and yes, human data as well,

02:08:23.180 | that show that pain thresholds are increased

02:08:25.260 | anytime PAG is activated because of the release

02:08:28.400 | of these endogenous opioids.

02:08:30.160 | There's also the immediate experience

02:08:35.060 | of whether or not a particular form of touch

02:08:37.240 | is pleasureful or not.

02:08:38.780 | And there, there's some very interesting biology

02:08:40.740 | that relates to really how those little wires

02:08:43.420 | from those DRGs innervate our skin.

02:08:45.520 | Work studies, I should say, done by David Ginty's lab

02:08:50.380 | at Harvard Medical School.

02:08:51.500 | The Ginty lab has spent years working

02:08:54.140 | on the somatosensory system, the touch system,

02:08:56.860 | has identified a particular category of neurons

02:09:00.380 | that innervate the skin,

02:09:01.460 | and then those neurons, of course,

02:09:02.500 | send that information up to the brain too,

02:09:04.620 | and they actually respond to direction of touch.

02:09:08.440 | Now, some of you might be more sensitive

02:09:10.240 | to this than others, but it turns out that certain hairs

02:09:14.880 | like to be deflected one way versus another.

02:09:17.820 | Whether or not you like cats or not,

02:09:20.620 | you can do this experiment.

02:09:22.000 | You can pet a cat in the direction that their fur lies.

02:09:25.120 | So it lies down in a particular direction.

02:09:26.760 | You'll notice that there's actually a gene

02:09:28.040 | that dictates that the hairs lie down

02:09:29.640 | in a particular direction.

02:09:30.760 | And if you pet them in a way that's cooperating

02:09:34.700 | with that direction, so not pushing the hairs up,

02:09:39.340 | but rather stroking the hairs on the back of the cat,

02:09:42.540 | what you'll notice is they often like that.

02:09:44.060 | Not all cats, some cats are pretty grouchy,

02:09:45.880 | but if you stroke their hair, they will often purr,

02:09:49.560 | they'll often push into you.

02:09:51.260 | If you were to stroke their hair in the opposite direction,

02:09:53.800 | pushing the hairs up against the direction

02:09:56.160 | that they want to lie down, cats do not like that.

02:09:59.320 | And it turns out people don't like that either.

02:10:01.120 | Some people do like to have their hair pushed

02:10:03.040 | in a direction against the direction

02:10:05.220 | in which it wants to lay down,

02:10:07.000 | but there is more typically a response

02:10:10.760 | of feeling like it's pleasureful for, for instance,

02:10:13.200 | when someone brushes or combs their hair

02:10:14.820 | in the direction that it wants to lay down.

02:10:16.400 | And that's because the way in which these neurons

02:10:19.160 | that innervate these hairs sends information

02:10:22.000 | up to the brain, bifurcates actually,

02:10:23.800 | it splits into brain centers that evoke a sense of pleasure

02:10:27.040 | or a sense of not pleasure.

02:10:28.520 | It's not necessarily pain.

02:10:30.100 | So you might find that certain people are very particular.

02:10:34.000 | They like to be touched in a certain way, but not others.

02:10:36.200 | You might be one of those people.

02:10:38.000 | And areas of our skin that have high density of receptors

02:10:41.620 | are very, very sensitive in a real way,

02:10:45.720 | in a real sense of the word, to patterns of touch

02:10:49.600 | and whether or not a touch is too firm or too light.

02:10:53.680 | And that will be modulated by overall levels of arousal.

02:10:58.560 | And when I talk about arousal,

02:10:59.760 | what I'm talking about is how alert or how sleepy we are.

02:11:02.460 | It is impossible to experience pain

02:11:05.280 | when we are deep in sleep.

02:11:07.620 | I don't mean sleeping like of the typical night sword.

02:11:09.600 | I mean of the anesthesia sword.

02:11:10.800 | That's the purpose of anesthesia,

02:11:12.320 | to bring the brain and body into a deep plane of rest,

02:11:15.240 | very deep, in fact.

02:11:16.760 | And it's very hard, if not impossible,

02:11:20.220 | to achieve or experience pleasure

02:11:22.640 | when we are in a very low state of arousal as well.

02:11:26.320 | When we are in heightened states of arousal,

02:11:29.080 | we can achieve pain, we can experience pain,

02:11:32.120 | and we can experience pleasure, okay?

02:11:35.040 | And under those heightened states of arousal,

02:11:37.520 | we are more sensitive, literally,

02:11:41.080 | the passage of electrical signals

02:11:43.080 | from those locations on the body that have heightened degrees

02:11:46.640 | or higher degrees, I should say, of receptors.

02:11:49.880 | Use your imagination.

02:11:51.160 | They include the lips, the face, the feet, and the genitals,

02:11:53.560 | and nearby areas, literally nearby areas.

02:11:56.720 | Under conditions of high arousal, two things happen.

02:12:01.620 | The ability to achieve or experience pleasure

02:12:04.040 | at those locations goes up,

02:12:05.920 | and our tolerance and our threshold for pain also goes up.

02:12:09.400 | So the principle here is that as our levels of arousal,

02:12:12.720 | that foundation of arousal goes up or down,

02:12:15.480 | so too goes up and down our ability

02:12:18.360 | to achieve pleasure and pain.

02:12:20.360 | And so these two extremes of being deep within anesthesia

02:12:22.840 | or another extreme is asleep

02:12:26.400 | or in heightened levels of arousal,

02:12:28.720 | our ability to achieve pleasure and pain

02:12:30.420 | are going to scale according to those.

02:12:32.560 | And this is why, and I'm certainly not suggesting this,

02:12:35.220 | but this is why some people will take stimulants

02:12:38.840 | or drugs of abuse that increase arousal

02:12:41.040 | in order to achieve pleasure of other kinds.

02:12:44.200 | The problem is is that those drugs,

02:12:46.160 | in particular things like cocaine and methamphetamine

02:12:48.540 | and amphetamine, become their own form of reinforcement,

02:12:51.920 | so much so that the person doesn't seek out

02:12:56.100 | any other form of excitement or arousal, okay?

02:12:59.840 | So today we weren't talking about addiction,

02:13:02.800 | we weren't necessarily talking about motivation,

02:13:04.960 | but we touched on those topics

02:13:06.240 | as sort of a precursor of what's to come.

02:13:08.880 | We talked about the pathways in the skin and in the brain

02:13:11.720 | and elsewhere in the body

02:13:13.200 | that control our sense of pleasure and pain.

02:13:14.980 | We described a number of different tools

02:13:16.840 | ranging from hypnosis to different supplements

02:13:19.080 | to electroacupuncture and various other tools

02:13:23.340 | that one could use to modulate

02:13:24.580 | your sense of pleasure or pain.

02:13:26.700 | And of course, in thinking about pleasure,

02:13:28.900 | we have to think about the dopamine system

02:13:30.380 | and the serotonin system

02:13:31.400 | and some of the related chemical systems.

02:13:33.520 | I realized that today's podcast

02:13:35.020 | had a lot of scientific details.

02:13:37.540 | We've timestamped everything for you

02:13:38.960 | so that you don't have to digest it all at once, of course.

02:13:42.300 | I don't expect that everyone would be able to understand

02:13:44.820 | all these details all at once.

02:13:46.680 | What's more important really

02:13:48.760 | is to understand the general principles

02:13:51.080 | of how something like pleasure and pain work,

02:13:53.640 | how they interact and the various cells and systems

02:13:56.340 | within the brain and body that allow them to occur

02:13:58.720 | and that modulate or change their ability to occur.

02:14:02.440 | And of course, your subjective experience

02:14:04.400 | of pleasure or pain.

02:14:05.680 | So I do hope that this was on whole

02:14:08.280 | more pleasureful than painful for you.

02:14:10.560 | If you're enjoying this podcast

02:14:11.880 | and you're learning from it and you'd like to support us,

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02:14:37.820 | There are other ways to support the podcast as well.

02:14:40.160 | We have a Patreon, that's patreon.com/andrewhuberman.

02:14:43.840 | And there you can support the podcast

02:14:45.720 | at any level that you like.

02:14:47.580 | In addition, please check out our sponsors

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02:14:51.780 | We only work with sponsors and brands

02:14:53.740 | that we absolutely love their products

02:14:55.980 | and that we wholeheartedly endorse

02:14:57.600 | and that we use ourselves.

02:14:59.080 | In addition, we've partnered with Thorne.

02:15:01.360 | Thorne is a supplement company

02:15:02.940 | and we've partnered with them

02:15:04.040 | because they have the highest levels of stringency

02:15:06.280 | in terms of the quality of the ingredients they use

02:15:09.000 | and the quantity of the ingredients they use.

02:15:11.560 | By quantity, I mean that unlike a lot

02:15:14.100 | of supplement companies out there,

02:15:15.940 | the amounts that are listed on the bottle

02:15:18.000 | are absolutely what you find in those capsules

02:15:20.280 | and tablets in the bottle.

02:15:22.240 | If you go to Thorne, that's T-H-O-R-N-E/u/huberman,

02:15:27.240 | you can see the supplements that I take

02:15:30.920 | and you can get 20% off any of those supplements

02:15:33.800 | as well as any of the other supplements that Thorne makes.

02:15:36.760 | Just go into the Thorne site through that portal,

02:15:39.000 | Thorne/u/huberman, and even if you navigate off

02:15:43.360 | from that location in the site,

02:15:45.100 | you'll get 20% off any of the items that you might select

02:15:47.840 | from other locations within the Thorne site.

02:15:49.880 | If you're not already following us on Instagram,

02:15:52.440 | it's Hubermanlab@instagram,

02:15:54.640 | and there I do various tutorials about neuroscience,

02:15:58.240 | offer neuroscience-related tools all backed by science.

02:16:01.480 | And last but not least,

02:16:02.880 | I thank you for your time and attention

02:16:04.760 | and thank you for your interest in science.

02:16:06.800 | (upbeat music)

02:16:09.380 | [MUSIC PLAYING]

How to Control Your Sense of Pain & Pleasure | Huberman Lab Podcast #32

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