back to indexHow to Control Your Sense of Pain & Pleasure | Huberman Lab Podcast #32
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman, and I'm a professor of neurobiology
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and ophthalmology at Stanford School of Medicine.
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Today, we continue our discussion of the senses,
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and the senses we are going to discuss
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are pain and pleasure.
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Pain and pleasure reflect two opposite ends of a continuum,
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a continuum that involves detection of things in our skin,
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and the perception, the understanding
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of what those events are.
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Our skin is our largest sensory organ,
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and our largest organ indeed.
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It is much larger than any of the other organs in our body,
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and it's an odd organ if you think about it.
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It has so many functions.
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It acts as a barrier between our organs
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and the outside world.
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It harbors neurons, nerve cells,
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that allow us to detect things like light touch
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or temperature or pressure of various kinds.
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And it's an organ that we hang ornaments on.
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People put earrings in their ears.
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People decorate their skin with tattoos
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and inks and other things.
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And it's an organ that allows us to experience
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either great pain or great pleasure.
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So it's a multifaceted organ,
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and it's one that our brain needs to make sense of
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in a multifaceted way.
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So today we're going to discuss all that,
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and most importantly, how you can experience more pleasure
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and less pain by understanding these pathways.
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We will also discuss things you can do,
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and if you wish, things you can take
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that will allow you to experience more pleasure
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and less pain in response
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to a variety of different experiences.
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Before I go any further,
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I want to highlight a particularly exciting area of science
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that relates to the skin and to sensing of pleasure and pain
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but has everything to do with motivation.
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Motivation is something that many people struggle with.
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Not everybody, but most people experience dips
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and peaks in their motivation,
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even if they really want something.
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How should we think about these changes in motivation?
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What do they reflect?
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Well, at a very basic level,
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they reflect fluctuations,
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changes in the levels of a chemical called dopamine.
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Most of us have heard of dopamine.
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Dopamine is a neuromodulator,
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meaning it modulates or changes the way
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that neurons, nerve cells, work.
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Most of us have heard that dopamine
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is the molecule of pleasure.
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However, that is incorrect.
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Dopamine is a molecule of motivation and anticipation.
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To illustrate how dopamine works,
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I want to highlight some very important work
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largely carried out by the laboratory
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of a guy named Wolfram Schultz.
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The Schultz Laboratory has done dozens
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of excellent experiments on the dopamine system
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and have identified something called
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reward prediction error.
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Although in some sense,
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you can think about it as reward prediction variance,
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changes in the levels of dopamine
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depending on whether or not you expect a reward
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and whether or not you get the reward.
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So I'm going to make this very simple.
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Dopamine is released into the brain and body
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and generally makes us feel activated and motivated
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and as if we have energy to pursue a goal.
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And it is released into the brain and body
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in anticipation of a reward.
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Measurements of dopamine have been made
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in animals and humans.
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What you find is that when we anticipate a reward,
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dopamine is released.
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We will put in the work to achieve that reward.
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That work could be mental work or physical work,
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but when the reward arrives,
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dopamine levels drop back down to baseline.
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When we receive a reward,
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dopamine levels go back down to baseline.
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So the way to envision this is you can just imagine
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a sort of increase in dopamine as we anticipate something,
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we're working towards it, we're working towards a goal,
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we're excited about seeing somebody or meeting somebody
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or receiving some reward,
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and then the reward comes and dopamine goes down.
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Now that's all fine and good,
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but there is a way to get much more dopamine
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out of that process and therefore a way
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to have much more motivation, energy, and focus,
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because those are the consequences of elevated dopamine.
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The way to do that is to not deliver the reward
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on an expected schedule.
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So experiments have been done
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where there's an anticipation of a reward, there's work,
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and then the reward only arrives every other
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or every third bout of work, okay?
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So this would be like getting a pat on the head
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if you're a dog or perhaps a child or an adult,
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or getting a monetary reward only for every third project
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or every third race that you win.
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Pick any kind of goal, it doesn't matter.
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These molecules don't care about what you're pursuing.
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They are a common currency of different types of activities.
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That's a regular reward schedule,
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and it will not alter the pattern of dopamine release
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that I described before.
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However, if the reward arrives intermittently,
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almost randomly, so you anticipate a reward as a maybe,
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it might come, it might come.
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Then you work, work, work, work, work, no reward.
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You repeat the work, work, work, work, work, work,
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and then you get a reward.
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So some trials you do, some trials you don't,
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and it's completely random.
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Under those conditions, the amplitude,
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the amount of dopamine that's released into your system,
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and the motivation to continue working hard
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or playing whatever kind of game you're playing,
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doubles or triples.
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And this is the basis of things like slot machines
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and gambling, and this is why so many people
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will give so much of their money up to casinos,
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and the casinos always win.
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Sometimes people walk away with more money
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than they came to the casino with,
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but the vast majority of the time,
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the house wins, as they say.
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And it's because they understand
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intermittent reward schedules.
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And you can apply this to stay motivated
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in your own pursuits.
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Rather than thinking about the pleasure of a reward,
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understand that dopamine is released
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in response to anticipation of a reward,
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and that is the fuel for work.
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And every once in a while at random, remove the reward.
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That's the way to continue to stay motivated,
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not to reward every action or every goal,
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and this is also true if you're trying to train up children
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or train up players on a team,
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you should not celebrate every win.
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I know that's a little counterintuitive.
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We're going to go more into the biology of dopamine
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and how it relates to the pleasure system
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later on in the podcast.
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But for now, understand intermittent reward schedules,
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harness the biology of dopamine
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in ways that can allow you
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essentially infinite motivation over time.
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Before I go any further,
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I want to acknowledge that this podcast is separate
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from my teaching and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information
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about science and science-related tools
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to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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So let's talk about pleasure and pain.
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I think we all intuitively understand
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what pleasure and pain are.
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Pleasure generally is a sensation in the body
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and in the mind that leads us to pursue more
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of whatever is bringing about that sensation.
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And pain is also a sensation in the body and in the mind
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that in general leads us to want to withdraw
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or move away from some activity or interaction.
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That's not always the case.
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Some people actively seek out pain.
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Some people somehow can't seem to engage with
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or experience pleasure, but most people operate
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on this basis of pleasure and pain.
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Scientists would call this a pettative behaviors,
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meaning behaviors that lead us to create an appetite
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for more of those behaviors
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and aversive behaviors, behaviors that make us want
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to move away from something.
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The simplest example of that would be putting your hand
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At some point, there would be a reflex
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or a deep desire to withdraw your hand.
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Tasting something delicious in general makes us want
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to eat more of that thing.
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Interactions with other people that we find delicious
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also make us want to interact with those people more.
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None of this is complicated or sophisticated.
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This is simply to illustrate the fact that pleasure
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and pain tend to evoke opposite responses,
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opposite behavioral responses
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and opposite emotional responses.
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So how does that come about?
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Well, it really comes about by an interaction
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that starts at one end of our body, meaning our skin,
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and the other end of the organs of our body,
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which is deep within the brain.
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So let's consider these two ends of the spectrum
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of pleasure and pain and what they contribute
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to those experiences of pleasure and pain.
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The organ that we call the skin, as I mentioned earlier,
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is the largest organ in our body.
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And throughout that organ, we have neurons,
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little nerve cells.
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Now, to be really technical about it,
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and the way I'd like you to understand it,
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is that the so-called cell body,
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meaning the location of a cell in which the DNA
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and other goodies, the kind of central factory of the cell,
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that actually sits right outside your spinal cord.
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So all up and down your spinal cord on either side
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are these little blobs of neurons,
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little collections of neurons.
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They have a name, if you'd like to know,
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for you aficionados or those who are curious,
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they're called DRGs, dorsal root ganglia.
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A ganglion is just a collection or a clump of cells.
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And those DRGs are really interesting
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because they send one branch that we call an axon,
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a little wire, out to our skin,
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also to our muscles and to our organs.
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But here we're talking about the skin.
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They send a wire out to our skin
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and that wire literally reaches up into the skin.
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It's actually in our skin.
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And they have another wire from that same cell body
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that goes in the opposite direction,
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which is up to our brain
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and creates connections within our brain
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in the so-called brainstem.
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What this means is that the neuron in your body
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that we call the DRG that sends a wire, an axon,
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to sense what's going on in your big toe
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and then sends another axon in the opposite direction
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into the base of your brain.
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That is the largest cell in your entire body of any kind,
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fat cell, muscle cell, nerve cell, et cetera.
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Those are extremely long cells.
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They can be a meter or more
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depending on how tall you happen to be.
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So we have these cells that have wires
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that go off in two different directions
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and the wire that's within our skin
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will respond to any number of different categories
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These wires are positioned within the skin
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to respond to mechanical forces, so maybe light touch.
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Some will only send electrical activity
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up toward the brain in response to light touch,
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meaning if you press on the skin really hard,
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they don't respond.
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You stroke the skin lightly with your fingertip or a feather
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and they respond very robustly.
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Others respond to course pressure, to hard pressure,
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but they won't respond to a light feather.
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For instance, others respond to temperature.
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So they will respond to the presence of heat
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or the presence of cold or changes in heat and cold.
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And still others respond to other types of stimuli
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like certain chemicals on our skin.
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Many of you have probably experienced the sensation
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of eating a hot pepper.
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Well, I don't recommend doing this,
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but were you to take a little slice of jalapeno
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or other hot pepper, habanero pepper or something like that
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and rub it on your skin,
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you would actually feel something at that location.
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And that's because that pepper doesn't just create
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a sensation within your mouth,
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it will create a similar sensation on your skin.
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So these neurons are amazing.
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They're collecting information of particular kinds
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from the skin throughout the entire body
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and sending that information up toward the brain.
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And what's really incredible,
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I just want you to ponder this for a second.
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What's really incredible is that the language
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that those neurons use is exactly the same.
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The neuron that responds to light touch
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sends electrical signals up toward the brain.
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The neurons that respond to cold or to heat
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or to habanero pepper,
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they only respond to the particular thing
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that evokes the electrical response.
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I should say that they only respond
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to the particular stimulus,
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the pepper, the cold, the heat, et cetera,
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that will evoke an electrical signal.
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But the electrical signals are a common language
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that all neurons use.
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And yet if something cold is presented to your skin
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even if you don't see that ice cube,
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if your eyes are closed or someone comes up behind you
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and puts an ice cube against your bare skinned back,
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you know that that sensation, that thing is cold.
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You don't misperceive it as heat
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or as a habanero pepper, okay?
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So that's amazing.
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What that means is that there must be another element
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in the equation of what creates pleasure or pain.
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And that element is your brain.
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Your brain takes these electrical signals
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and interprets them partially based on experience,
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but also there are some innate,
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meaning some hardwired aspects of pain and pleasure sensing
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that require no experience whatsoever.
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A child doesn't have to fall down,
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but wants to know on that first fall that hurt.
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They don't have to touch a flame, but once,
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and the very first time they will withdraw their hand
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So no prior experience is required.
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Other things, prior experience is required.
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For instance, if you're somebody that has
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a intense aversion to spicy foods,
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that's probably because you've tasted spicy foods before.
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Likewise, if you really like sweet foods,
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it's probably because you've tasted them before.
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So you can start to make predictions
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based on prior experience,
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but the pain and pleasure system
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don't need prior experience.
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What they need is a brain that can interpret
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these electrical signals.
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They can take these electrical signals
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and somehow create what we call pleasure
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and pain out of them.
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So what parts of the brain?
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Well, mainly it's the so-called somatosensory cortex,
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the portion of our neocortex,
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which is on the outside of our brain,
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the kind of bumpy part, not kind of,
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if you have a normally formed brain, it will be bumpy.
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If you have a smooth brain, that's not good.
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Some animals just have a smooth brain.
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Humans have a bumpy brain,
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which means it has a very large surface area.
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And those bumps are because you squeezed it like a pizza
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and bunched it all up and put inside the skull.
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That means you have a lot of neurons.
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And in your somatosensory cortex,
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you have a map of your entire body surface.
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That map is called a homunculus.
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And if we were to take your cortex and lay it out on a table,
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I've actually done this with the cortices
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of various animals and humans included.
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What you would find is that there's literally a map
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of your entire body surface,
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but it wouldn't look exactly like you.
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This map would be very distorted.
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Why would it be distorted?
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Well, certain areas of your body
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have a much denser innervation as we call it,
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or put simply many more of these sensory wires
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from these DRGs within your skin.
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So this map of you that exists in your brain,
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and you do have one of these on each side of your brain,
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so you have two of these maps, two homunculi, that is you.
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It's your representation of touch,
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including pleasure and pain.
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And in that map, your lips are enormous
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and your back is very, very small.
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And the area around your eyes
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and the area representing your face is absolutely enormous.
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So you would look like some sort of odd, weird clay doll
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from some sort of bizarre late night animation thing,
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and just imagine the psychedelic experience
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of that character of you,
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and that's what it would look like.
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But it's not randomly organized.
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To the contrary, it's highly organized
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in a very particular way,
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which is that the areas of your skin
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that have the highest density of these sensory receptors
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are magnified in your brain.
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So it's sort of like having more pixels
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in a certain part of a camera than others,
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and in doing that, allowing higher resolution,
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in this case of touch, not a vision,
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but of touch sensation in certain parts of your body.
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What are the areas that are magnified?
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Well, the lips, the face, the tips of the fingers,
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the feet, and the genitals.
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And so this map of you has very large lips, face,
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tips of fingers, bottoms of feet, and genitals.
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And that's because the innervation,
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the number of wires that go into those regions of your body
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far exceeds the number of wires for sensation of touch
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that go to other areas of your body.
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You can actually experience this in real time right now
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by doing a simple experiment
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that we call two-point discrimination.
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Two-point discrimination is your ability
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to know whether or not two points of pressure
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are far apart, near each other,
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or you actually could perceive incorrectly
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as one point of pressure.
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You might want a second person to do this experiment.
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Here's how you would do it.
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You would close your eyes.
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That person would take two fine points.
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Don't make them too sharp, please.
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So it could be two pencils or pens or the backs of pens.
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Two pens, I'm holding in my hands.
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If you're just listening to this, I'm just holding two pens.
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My favorite pens, these Pilot V5s or V7s, which I love.
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If you were to close your eyes
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and I were to take these two pens
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and put their points close together about a centimeter apart
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and present them to the top of your hand,
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I'm just going to do that now to myself,
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you, even though your eyes were closed,
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you would be able to perceive
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that that was two points of pressure
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presented simultaneously to the top of your hand.
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However, if I were to do this to the middle of your back,
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you would not experience them as two points of pressure.
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You would experience them as one single point of pressure.
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In other words, your two-point discrimination is better,
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is higher on areas of your body
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which have many, many more sensory receptors.
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You are more sensitive at those locations.
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Now, this makes perfect sense
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once you experience it or you hear about it.
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However, most of us don't really appreciate how important
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and what a profound influence
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this change in density of receptors
link |
across our body surface has.
link |
And we can go a step further
link |
and describe another feature of the way that you're built
link |
and the way that you experience pleasure and pain,
link |
which is called the dermatome.
link |
The dermatome is literally the way
link |
in which your body surface is carved up
link |
into different territories,
link |
much like a map of the United States
link |
is carved up into different territories of states
link |
and counties, et cetera.
link |
The dermatome is the way in which neurons connect
link |
to different parts of your body.
link |
Now, you've actually experienced the dermatome before.
link |
The dermatome is when you have a neuron
link |
that connects to a particular area of the body
link |
and that neuron doesn't just send one little wire out
link |
like one little line and go up into the skin
link |
to detect mechanical or thermal or chemical stimuli.
link |
It actually sends many branches out like a tree.
link |
But remember, those branches of the tree
link |
come from one single neuron.
link |
Now, occasionally what will happen
link |
is you will experience something like cold or heat
link |
or pain or tingling on a patch of your body.
link |
And occasionally that patch of body
link |
will actually have a very cleanly demarcated boundary,
link |
a very stark boundary with the areas around it.
link |
A good example of this would be the herpes simplex 1 virus,
link |
which if one has this virus,
link |
and I should mention that somewhere between 80 and 90%
link |
of people have this virus.
link |
This is not a sexually transmitted virus.
link |
This is a virus that's transmitted very easily
link |
between people through various forms of contact,
link |
non-sexual contact.
link |
It's present in children and it's present in adults.
link |
And most people get it.
link |
Some get symptoms and some don't.
link |
Some get recurring symptoms, some don't.
link |
We can talk about that at the end if you like.
link |
But this virus lives on what's called
link |
the fifth cranial nerve, also called the trigeminal nerve.
link |
The trigeminal nerve sends branches out to the lips,
link |
to the eyes and to certain portions of the face.
link |
So for those of you listening,
link |
I've just kind of put my right hand across my face
link |
and to sort of simulate the three branches,
link |
the trigeminal aspect of this nerve.
link |
Now, when the herpes virus flares up,
link |
as they say in response to stress or other factors,
link |
the virus inflames that nerve
link |
and people experience tingling and pain on the nerve.
link |
Sometimes they'll get a cold sore or a blister
link |
on their lip or near their mouth.
link |
Sometimes they'll get a collection of those.
link |
And that's because that dermatome is actually inflamed.
link |
Now, other people will experience
link |
something like shingles, right?
link |
It's a fairly common viral infection.
link |
And what they'll notice is they'll get a rash
link |
that has a boundary.
link |
It's like, they'll get a bunch of bumps,
link |
sometimes blisters, and it'll have a sharp boundary.
link |
That boundary exists because the virus exists on the nerve.
link |
And so it actually is boundaried
link |
with the neighboring area of the body
link |
that's receiving input from another nerve.
link |
And that one doesn't have the virus living on it.
link |
So anytime you see a rash or a pattern on the body surface,
link |
on the skin, that has a pretty stark boundary,
link |
chances are that's an event that's impacting the dermatome.
link |
I've experienced this before,
link |
not through herpes simplex,
link |
but through the experience of having a lot of blood
link |
sort of aggregating in a kind of a segment
link |
across the front of my face.
link |
It was really bizarre.
link |
I looked in the mirror and I thought,
link |
what is going on here?
link |
I was having an allergic reaction to something I'd eaten.
link |
And that allergic reaction clearly was affecting
link |
one of the nerves and therefore the dermatome.
link |
And what it showed up was,
link |
it was almost like someone had drawn lines on my face
link |
that said, okay, this rash or this reaction rather
link |
can happen here, but not in the region right next to it.
link |
Whenever you see that,
link |
chances are it's a reaction of the nerves of the dermatome.
link |
So you'll start to see these things more and more
link |
when you start to look for them.
link |
You don't always have to have a viral infection
link |
to experience this.
link |
Sometimes you'll just experience tingling
link |
or even a pleasant sensation,
link |
and it will be restricted in kind of a strict boundary
link |
on one location of your body surface and not another.
link |
Not corresponding to an organ like, okay, this arm,
link |
or just your feet or something like that,
link |
but just a segment.
link |
It's almost like someone outlined a particular area
link |
of your body surface.
link |
That's the dermatome.
link |
Okay, so you've got sensors in the skin
link |
and you've got a brain that's going to interpret
link |
what's going on with those sensors.
link |
In fact, we can take an example of a sudden rash
link |
or inflammation at one location in the dermatome,
link |
and we can ask what would make it hurt?
link |
What would make it worse?
link |
What would make it go away?
link |
And believe it or not, your subjective interpretation
link |
of what's happening has a profound influence
link |
on your experience of pleasure or pain.
link |
There are several things that can impact these experiences,
link |
but the main categories are expectation.
link |
So sort of whether or not you thought or could expect
link |
that this thing was going to happen, right?
link |
If someone tells you this is going to hurt,
link |
I'm going to give you an injection right here.
link |
It might hurt for a second.
link |
That's very different and your experience of that pain
link |
will be very different than if it happened suddenly
link |
There's also anxiety, how anxious or how high or low
link |
your level of arousal, autonomic arousal,
link |
that's going to impact your experience of pleasure or pain.
link |
How well you slept and where you are
link |
in the so-called circadian or 24-hour cycle.
link |
Our ability to tolerate pain changes dramatically
link |
across the 24-hour cycle.
link |
And as you can imagine, it's during the daylight waking
link |
hours that we are better able to tolerate.
link |
We are more resilient to pain
link |
and we are better able to experience pleasure.
link |
At night, our threshold for pain is much lower.
link |
In other words, the amount of mechanical or chemical
link |
or thermal, meaning temperature stimulated
link |
that can evoke a pain response
link |
and how we would rate that response is much lower at night.
link |
And in particular, in the hours between 2 AM and 5 AM
link |
if you're on a kind of standard circadian schedule.
link |
And then the last one is our genes.
link |
Pain threshold and how long a pain response lasts
link |
is in part dictated by our genes.
link |
And later I'm going to discuss this myth
link |
or whether or not it's really a myth
link |
as to whether or not certain people in particular redheads,
link |
people who have red pigmented hair and fair skin,
link |
whether or not their pain thresholds differ.
link |
And to just give you a little sneak peek into that,
link |
And it's because of a genetic difference
link |
in a particular gene and a particular pattern of receptors
link |
in the skin that are related
link |
to the pigmentation of hair and skin.
link |
So we have expectation, anxiety, how well we've slept,
link |
where we are in the so-called 24 hour circadian time
link |
So let's talk about expectation and anxiety
link |
because those two factors can powerfully modulate
link |
our experience of both pleasure and pain
link |
in ways that will allow us to dial up pleasure if we like
link |
and to dial down pain if indeed that's what we want to do.
link |
So let's talk about expectation and anxiety
link |
because those two things are somewhat tethered.
link |
There are now a number of solid experiments,
link |
both in animal models and in humans
link |
that point to the fact that if we know
link |
a painful stimulus is coming,
link |
that we can better prepare for it mentally
link |
and therefore buffer or reduce the pain response.
link |
However, the timing in which that anticipation occurs
link |
is vital for this to happen.
link |
And if that timing isn't quite right,
link |
it actually can make the experience of pain far worse.
link |
So here I'm summarizing a large amount of literature,
link |
but essentially if subjects are warned
link |
that a painful stimulus is coming,
link |
their subjective experience of that pain is vastly reduced.
link |
However, if they are warned just two seconds
link |
before that pain arrives, it does not help.
link |
It actually makes it worse.
link |
And the reason is they can't do anything mentally
link |
to prepare for it in that brief two second window.
link |
Similarly, if they are warned about pain that's coming
link |
two minutes before a painful stimulus is coming,
link |
electric shock or a poke or cold stimulus
link |
or heat stimulus that's pretty extreme,
link |
that also makes it worse because their expectation ramps up
link |
the autonomic arousal, the level of alertness
link |
is all funneled toward that negative experience
link |
So how soon before a painful stimulus
link |
should we know about it if the goal
link |
is to reduce our level of pain?
link |
And the answer is somewhere between 20 seconds
link |
and 40 seconds is about right.
link |
Now I'm averaging across a number of different studies,
link |
but if you have about 20 seconds or 40 seconds
link |
advance warning that something bad is coming,
link |
you can prepare yourself for that.
link |
But the preparation itself and the arousal
link |
that comes with it, the kind of leaning in,
link |
okay, I'm either going to relax myself
link |
or I'm going to really kind of dig my heels in
link |
and kind of meet the pain head on,
link |
that seems to be the optimal window.
link |
This can come in useful in a variety of contexts,
link |
but I think it's important because what it illustrates
link |
is that it absolutely cannot be just the pattern of signals
link |
that are arriving from the skin from these DRGs,
link |
these neurons that connect to skin
link |
that dictates our experience of pain or pleasure.
link |
There has to be a subjective interpretation component
link |
and indeed that's the case.
link |
So let's talk about the range of pain experiences
link |
and from that, we will understand better
link |
what the range of pleasure experiences are
link |
that different people have,
link |
because we are all different in terms of our pain threshold.
link |
First of all, what is pain threshold?
link |
Pain threshold has two dimensions.
link |
The first dimension is the amount of mechanical or chemical
link |
or thermal stimulation that it takes for you or me
link |
or somebody else to say, I can't take that anymore, I'm done.
link |
But there's another element as well,
link |
which is how long the pain persists.
link |
I'll just describe myself, for example,
link |
I don't consider myself somebody
link |
who has a particularly high pain threshold.
link |
I don't think it's particularly low either,
link |
but I wouldn't consider myself somebody
link |
that has a particularly high pain threshold.
link |
When I stub my toe against the corner of the bed,
link |
it absolutely hurts.
link |
But one thing that I've noticed
link |
is that I have very sharp inflections,
link |
very high inflections in my perception of pain
link |
and then they go away quickly.
link |
I don't know if that's adaptive or not, it's probably not,
link |
but my experience of pain is very intense, but very brief.
link |
Other people experience pain
link |
in a much kind of slower rising, but longer lasting manner.
link |
And to just really point out how varied we all are
link |
in terms of our experience of pain,
link |
let's look to an experiment.
link |
There have been experiments done
link |
at Stanford School of Medicine and elsewhere,
link |
which involved having subjects put their hand
link |
into a very cold vat of water
link |
and measuring the amount of time
link |
that they kept their hand in that water.
link |
And then they would tell the experimenter very quietly
link |
how painful that particular stimulus was
link |
on a scale of one to 10,
link |
so-called Likert scale for you aficionados.
link |
That simple experiment revealed
link |
that people experience the same thermal,
link |
in this case, cold stimulus, vastly different.
link |
Some people would rate it as a 10 out of 10, extreme pain.
link |
Other people would rate it as barely painful at all,
link |
Other people, a three.
link |
Other people, a five, et cetera.
link |
Now what's interesting is that the same thing is true
link |
for experience of a hot painful stimulus,
link |
120 degree hot plate where you have to put your hand on it.
link |
And then at some point you remove your hand.
link |
Some people are able to keep their hand
link |
on there the whole time,
link |
but people rate that experience as very painful,
link |
a little bit painful or moderately painful
link |
depending on who they are.
link |
Now that's interesting,
link |
probably not that surprising, however.
link |
But what is very interesting is that
link |
when the same experiment was done on medical doctors
link |
or medical doctors in training,
link |
they too, of course, experienced pain
link |
through a range of subjective experiences.
link |
Some of them, just like any other person off the street,
link |
said a particular stimulus of a particular temperature
link |
Others said it wasn't painful at all.
link |
And some said it was moderately painful.
link |
And that turns out to be vitally important
link |
for the treatment of pain
link |
because pain is not an event in the skin.
link |
Pain is a subjective emotional experience.
link |
You may have heard that we have a particular category
link |
of these DRGs that innervate the skin,
link |
which are called nociceptors.
link |
Nociceptor comes from the word nocera, I believe it is,
link |
which means to harm.
link |
However, nociceptors don't carry information about pain.
link |
They carry information about particular types of stimuli
link |
impacting the skin.
link |
And then the brain assigns a value, a valence to it,
link |
a label, and says that's painful.
link |
And where people draw the line
link |
between not painful and painful varies.
link |
Now, because physicians are people
link |
and because physicians treat pain,
link |
what we know from a lot of data now
link |
is that if someone comes into the clinic
link |
and says they're experiencing chronic pain
link |
or whole body pain or acute pain after an injury
link |
it doesn't really matter what the cause is
link |
or even if there's a cause at all.
link |
How the doctor reacts to that report of the patient's pain
link |
will dictate in many cases the course of treatment.
link |
And of course, doctors, their goal is to treat the patient
link |
according to the patient's needs, not their own.
link |
And that's what good doctors do.
link |
However, it's been found,
link |
and I think now there is work being done
link |
to try and change this.
link |
But if a doctor has a very high threshold for pain,
link |
their interpretation of somebody else's report of pain
link |
is going to be different.
link |
They might not discount the patient, right?
link |
This doesn't necessarily mean that they think,
link |
oh, this person, their pain is irrelevant.
link |
In fact, from having a high threshold for pain,
link |
if someone comes in and says, I'm in extreme pain,
link |
that doctor probably thinks, wow,
link |
this has to be really, really extreme.
link |
But they can be talking about two different experiences.
link |
Similarly, if a physician has a very low threshold for pain
link |
and someone comes in and says,
link |
yeah, I'm experiencing some pain in my back.
link |
I've got the sciatica thing,
link |
but it's a little bit uncomfortable.
link |
It's like, I don't know, like a four out of 10.
link |
Well, that physician might interpret that four out of 10
link |
as a pretty extreme sense of pain
link |
or a pretty extreme experience of pain.
link |
And so you can start to see how the subjective nature
link |
of pain can start to have real impact
link |
on the treatment of pain
link |
because treatment of pain is carried out by physicians.
link |
In fact, there is no objective measure of pain.
link |
We can ask how long somebody can keep their hand
link |
on a hot plate or in a cold bath.
link |
You can do various experiments.
link |
They even have some extreme experiments
link |
where they'll shave a portion of the leg
link |
and they'll put on a very painful chemical compound
link |
and see how long people can tolerate that.
link |
These are very uncomfortable experiments,
link |
as you can imagine.
link |
But in general, we don't have a way
link |
of measuring somebody else's subjective experience of pain.
link |
There's no blood pressure measure.
link |
There's no heart rate beats per minute measure of pain.
link |
So one of the great efforts of neuroscience
link |
and of medicine is to try and come up
link |
with more objective measures of pain.
link |
Similarly, pleasure is something that we all talk about.
link |
Ooh, that feels so good, or I love that,
link |
or more of that, please, or less of that.
link |
But we have no way of gauging
link |
what other people are experiencing
link |
except what they report through language.
link |
And so this is really just to illustrate
link |
that this whole thing around pain isn't a black box.
link |
We do have an understanding of the elements.
link |
There are elements in the skin.
link |
There's elements of the brain.
link |
There's expectation, anxiety, sleep, and genes,
link |
but that it is very complicated.
link |
And yet there are certain principles
link |
that fall out of that complicated picture
link |
that can allow us to better understand
link |
and navigate this axis that we call the pleasure pain axis.
link |
So rather than focus on just the subjective nature of pain,
link |
let's talk about the absolute qualities of pain
link |
and the absolute qualities of pleasure
link |
so that we can learn how to navigate those two experiences
link |
in ways that serve us each better.
link |
First of all, I want to talk about heat and cold.
link |
We do indeed have sensors in our skin
link |
that respond to heat and cold.
link |
And for any of you that have entered a cold shower
link |
or a cold body of water of any kind or ice bath, et cetera,
link |
you will realize that getting into cold
link |
is much harder if you do it slowly.
link |
Now, despite that, people tend to do it very slowly.
link |
I have noticed an enormous variation
link |
with which people can embrace the experience of cold.
link |
I noticed it because I do some work with athletes
link |
and I do some work with military
link |
and I do some work with the general public.
link |
And one of the best tests of how somebody can handle pain
link |
is to ask them to just get into an ice bath.
link |
It's not a very sophisticated experience,
link |
but it really gets into the core of the kind of circuitry
link |
that we're talking about, both in the skin and in the brain.
link |
Some people, regardless of sex, regardless of age,
link |
and regardless of physical ability
link |
can just get into the cold.
link |
They're somehow able to do it.
link |
Now, I don't know what their experience of the cold is
link |
and neither do you, you only know your experience,
link |
but they're able to do that.
link |
Some do it quickly, some do it slowly.
link |
Others find the experience of cold to be so aversive
link |
that they somehow cannot get themselves in.
link |
They start quaking, they start complaining
link |
and many of them just simply get out.
link |
They can't do it, some don't even get in past their knees.
link |
This isn't necessarily about pain threshold,
link |
but it's related to that.
link |
I think it can be helpful to everyone to know
link |
that even though it feels better at a mental level
link |
to get into the cold slowly and people ask,
link |
oh, I just want to get in slowly, I want to take my time.
link |
It is actually much worse
link |
from a neurobiological perspective.
link |
The neurons that sense cold respond
link |
to what are called relative drops in temperature.
link |
So it's not about the absolute temperature of the water,
link |
it's about the relative change in temperature.
link |
So as you move from a particular temperature,
link |
whether or not it's in the air next to an ice bath
link |
or cold shower, or from a body of water that's warm
link |
to a body of water that's colder,
link |
or sometimes in the ocean, you'll notice it's warm
link |
and then as you swim out further,
link |
you'll get into a pocket of water where it's much colder.
link |
That's when the cold receptors in your skin start firing
link |
and sending signals up to your brain.
link |
Therefore, you can bypass these signals going up to the brain
link |
with each relative change, one degree change,
link |
two degrees change, et cetera,
link |
by simply getting in all at once.
link |
In fact, it is true.
link |
And maybe you've been told this before and it is true
link |
that if you get into cold water up to your neck,
link |
it's actually much more comfortable
link |
than if you're halfway in and halfway out.
link |
And that's because of the difference in the signals
link |
that are being sent from the cold receptors
link |
on your upper torso,
link |
which is out of the water in your lower torso.
link |
Now, I wouldn't want anyone to take this to mean
link |
that they should just jump into an unknown body of water.
link |
There are all sorts of factors like currents.
link |
And if it's very, very cold, yes, indeed,
link |
you can stop the heart.
link |
People can have heart attacks
link |
from getting into extremely cold water
link |
like a melted mountain stream that's been frozen all winter
link |
or has been very, very cold or has a snowpack going into it.
link |
If it's very cold, you can indeed have a heart attack.
link |
So please be smart about how cold
link |
and what bodies of cold water
link |
you happen to put yourself into.
link |
But it is absolutely true that provided it's safe,
link |
getting into a cold water is always going to be easier
link |
to do quickly and is going to be easier
link |
to do up to your neck.
link |
In fact, you actually want to get your shoulders submerged.
link |
There are a number of other things you can do
link |
if you really want and it's safe to do.
link |
You can put your face under
link |
and activate the so-called dive reflex,
link |
which also makes the tolerance of cold easier,
link |
believe it or not.
link |
So it's very counterintuitive.
link |
It's like getting into cold water faster
link |
and more completely,
link |
you will experience as less uncomfortable, less cold.
link |
And indeed that's the case.
link |
And that's because these cold receptors
link |
are measuring every relative drop in temperature.
link |
So every single one is graded as we say in biology,
link |
it's not absolute.
link |
As an additional point,
link |
if you're sitting in a body of cold water
link |
and it's not circulating,
link |
you'll notice that you start to warm up a little bit,
link |
or even if you feel like you're freezing cold,
link |
if you move and that water around you moves of course,
link |
then you'll notice it's got even colder.
link |
And that's because there's a thermal layer.
link |
You're actually heating up the water
link |
that surrounds your body,
link |
like a halo around every aspect of your body,
link |
a sort of silhouette of you of heat
link |
where you're heating that water.
link |
When you move, you disrupt that thermal layer.
link |
Now heat is the opposite.
link |
Heat and the heat receptors in your skin
link |
respond to absolute changes in temperature.
link |
And this is probably because our body and our brain
link |
can tolerate drops in temperature
link |
much better than it can tolerate
link |
increases in temperature safely.
link |
So when you move from say a standard outdoor environment,
link |
I mean, here in the States,
link |
we measure in terms of Fahrenheit.
link |
So maybe it's a 75 or an 80 degree or even 90 degree day,
link |
and you get into a hundred degree sauna,
link |
or if you're in a cool air conditioned building
link |
and you go outside and it's very warm outside,
link |
you sort of feel like the heat hits you all at once.
link |
Boom, hits you all at once, kind of like a slap in the face.
link |
But then it will just stay at that level.
link |
Your body will acclimate to that particular temperature.
link |
However, if that temperature is very, very high,
link |
you'll notice that your experience of that heat
link |
and your experience of kind of pain and discomfort
link |
and your desire to get out of that heat will tend to persist.
link |
You don't really adapt in the same way.
link |
And certain people who are really good
link |
at handling very hot sauna get better at this.
link |
You learn to calm your breathing, et cetera,
link |
lower your autonomic arousal.
link |
Obviously you don't want to let
link |
your body temperature go too high
link |
because if neurons cook, they die.
link |
If neurons die, they don't come back.
link |
Many people unfortunately harm themselves with hyperthermia.
link |
Everyone has a different threshold for this,
link |
but in general, you don't want your body temperature
link |
to go up too high.
link |
That's why a fever of like 103
link |
starts to become worrisome, 104.
link |
You really get concerned if,
link |
and it goes up into that range or higher,
link |
that's when you need to really cool down the body
link |
or get to the hospital so they can cool you down.
link |
Heat is measured in absolute terms by the neurons.
link |
So gradually moving into heat makes sense
link |
and finding that threshold,
link |
which is safe and comfortable for you,
link |
or if it's uncomfortable,
link |
at least resides within that realm of safety.
link |
So that's heat and cold.
link |
And those are sort of non-negotiables.
link |
You can try and lower your level of arousal.
link |
In fact, many people who will get into a cold shower
link |
and ice bath, I think the recommendation that I always give
link |
is that you have two possible approaches to that.
link |
You can either try and relax yourself,
link |
kind of just stay calm within the cold,
link |
or you can lean into it.
link |
You can actually take mental steps
link |
to generate more adrenaline
link |
to kind of meet the demands of that cold.
link |
And at some point we'll do a whole episode
link |
on how to use cold and heat to certain advantages.
link |
We've done a little bit of this in past episodes,
link |
using the cold to supercharge human performance
link |
and things of that sort.
link |
But in general, cold is measured in relative terms,
link |
and therefore getting in all at once is a good idea
link |
provided you can do it safely,
link |
and heat is measured in absolute levels
link |
by your brain and body,
link |
and therefore you want to actually move into it gradually.
link |
So it's kind of the inverse of what you might think.
link |
One of the most important things to understand
link |
about the experience of pain
link |
and to really illustrate just how subjective pain really is
link |
is that our experience of pain
link |
and the degree of damage to our body
link |
are not always correlated.
link |
And in fact, sometimes can be in opposite directions.
link |
A good example of this would be x-rays.
link |
We all occasionally get x-rays,
link |
at least in the US we get x-rays
link |
when we go to the dentist from time to time.
link |
And the occasional x-ray might be safe
link |
depending on who you are,
link |
provided you're not pregnant, et cetera.
link |
I've gone to the dentist,
link |
they put you in the chair,
link |
they cover you with a lead blanket,
link |
and then they run behind the screen to protect themselves,
link |
and they beam you with the x-rays
link |
to get a picture of your teeth and your jaws
link |
and your skull, et cetera.
link |
Well, if you were to get too many x-rays,
link |
you could severely damage the tissues of your body,
link |
but you don't experience any pain during the x-ray itself.
link |
In contrast, you can think that your body is damaged
link |
and experience extreme pain,
link |
and yet your body can have no damage.
link |
A classic example of this was published
link |
in the British Journal of Medicine
link |
in which a construction worker fell from,
link |
I think it was a second story which he was working,
link |
and a nail went up and through his boot,
link |
and he looked down and he saw the nail
link |
going through his boot,
link |
and he was in absolute excruciating pain.
link |
They took him to the hospital,
link |
and because the nail was so long
link |
and because of where it had entered and exited the boot,
link |
they had to cut away the boot
link |
in order to get to the nail.
link |
And when they did that,
link |
they revealed that the nail had passed
link |
between two of his toes.
link |
It had actually failed to impale his body in any way.
link |
And yet the view, the perception of that nail
link |
entering his boot at one end
link |
and exiting the boot at the other
link |
was sufficient to create the experience of a nail
link |
that had gone through his foot.
link |
And the moment he realized
link |
that that nail had not gone through his foot,
link |
the pain completely evaporated.
link |
And this has been demonstrated numerous times.
link |
People that work in emergency rooms
link |
actually see variations on this, not always that extreme,
link |
but many times what we see
link |
and how we perceive that wound or that event
link |
has a profound influence on how we experience pain.
link |
And I mention this not just because
link |
it's a kind of sensational and fantastic example
link |
of this extreme subjective nature of pain,
link |
but also because it brings us back to this element,
link |
which is we don't know how other people feel,
link |
not just about pain, but about pleasure.
link |
We have some general sense of whether or not an event
link |
ought to be painful or pleasurable,
link |
but actually we barely understand how we feel,
link |
let alone how other people feel.
link |
And we can be badly wrong about how we feel,
link |
meaning we can misinterpret our own sense of pain
link |
or our own sense of pleasure
link |
depending on what we see with our eyes
link |
and what we hear with our ears.
link |
So we hear a scream, like a shrill scream,
link |
and we think it must be pain.
link |
And if we look at something that's happening to somebody
link |
and it fits a prior category or a prior representation
link |
of what we would consider painful stimulus,
link |
well, then we think that they're in extreme pain,
link |
but actually they might not be in pain at all.
link |
Now, this highly subjective nature of pain
link |
and the way in which we use our visual system
link |
to interpret other people's pain and our own pain
link |
has actually been leveraged to treat
link |
a very extreme form of chronic pain.
link |
And it's an absolutely fascinating area
link |
of biology and neuroscience.
link |
And it's one that we can actually all leverage
link |
toward reducing our own levels of pain
link |
whenever we are injured, or believe it or not,
link |
even in chronic pain.
link |
To describe this area of science
link |
requires a kind of extreme example.
link |
I want to be clear that even if you don't suffer
link |
from this extreme example,
link |
there's relevance and a tool to extract for you.
link |
The extreme example is that of an amputated digit,
link |
meaning one of your fingers or your toes,
link |
or of an amputated limb.
link |
So people that have digits or limbs that are gone,
link |
missing from an injury or surgical removal,
link |
will often have the experience that it's still there,
link |
the so-called phantom limb phenomenon.
link |
Now, why would that be?
link |
Well, when you remove a particular finger or limb,
link |
obviously that finger and limb is gone,
link |
and the dorsal root ganglion neuron
link |
that would normally send a wire
link |
out to that particular region of the body,
link |
that wire is no longer there
link |
because that portion of the body is no longer there.
link |
And in some cases, those neurons die,
link |
almost always, but not always.
link |
However, the map, your so-called homunculus,
link |
your representation of yourself in the brain
link |
And this map, the so-called homunculus map
link |
that you have and that I have is very plastic.
link |
And so as a consequence,
link |
areas of the map that are adjacent to one another
link |
can actually start to invade other areas of the map.
link |
So for instance, there are neuroimaging studies
link |
that have documented that somebody that has, say,
link |
a complete removal of their left arm,
link |
the representation of their left arm
link |
still exists in the cortex.
link |
And experimentally,
link |
if one is to stimulate that area of the cortex,
link |
that person, and if that person were you,
link |
would experience having that arm,
link |
that it were being stimulated,
link |
even though it's not there.
link |
Now, someone who has an amputated arm
link |
doesn't need to have their brain stimulated
link |
in order to have the experience
link |
of that phantom limb being present.
link |
In fact, many people who have limbs that were amputated
link |
feel as if that limb is still present,
link |
even though obviously it's not.
link |
And no matter how many times they look to the stump
link |
and just see a stump,
link |
somehow it doesn't reorganize that homunculus
link |
so-called central brain map.
link |
Now, that would be fine.
link |
You might even think that would be better,
link |
better to think you have the arm there
link |
than to feel as if it's missing.
link |
And yet many people who have amputated limbs
link |
report phantom limb pain.
link |
They don't feel that the arm
link |
is just casually draped next to them.
link |
They feel as if it's bunched up and it's an extreme pain.
link |
In fact, this kind of contorted stance
link |
that I'm taking right here in my chair
link |
is not unlike the way that these patients describe this.
link |
They feel as if it's kind of cramped up.
link |
It's very uncomfortable for them.
link |
Now, an absolutely creative,
link |
and you could even say genius scientist
link |
by the name of Ramachandran,
link |
that's actually his last name.
link |
His complete name is a little bit more complicated.
link |
So you all almost always hear Ramachandran
link |
referred to as Ramachandran or VS Ramachandran
link |
because his full name is Villayanur Subramanian Ramachandran.
link |
So a lot of letters in there, a lot of vowels.
link |
But Ramachandran is a neuroscientist.
link |
He was actually a colleague of mine
link |
when my lab was formerly
link |
at the University of California, San Diego.
link |
He's done a lot of work on this phantom limb phenomenon.
link |
And Ramachandran actually started off as a vision scientist.
link |
And he understood the power of the visual system
link |
in dictating our experience of things like pain and pleasure.
link |
And so what he developed was a very low technology
link |
yet neuroscientifically sophisticated treatment
link |
It consisted of a box,
link |
literally a box that had mirrors inside of it.
link |
And the patient would put the intact hand or limb
link |
And obviously they couldn't put the amputated limb
link |
into the other side
link |
but because of the configuration of the mirrors,
link |
it appeared as though they had two symmetric limbs
link |
And then he would have them look at that limb
link |
and move it around.
link |
And as they would do this,
link |
they would report real time movement
link |
or I should say real time perception of movement
link |
in the phantom limb.
link |
Now, this is absolutely incredible but makes total sense
link |
when you think about the so-called top down
link |
or contextual modulation of our sensory experience.
link |
Remember, it's anticipation, it's anxiety,
link |
it's interpretation of what's happening
link |
that drives our perception of what's happening.
link |
And so as he would have these patients
link |
move their intact limb to a more relaxed position,
link |
the patients would feel as if the phantom limb
link |
And this was used successfully to treat phantom limb pain
link |
in a number of different people.
link |
It didn't always work.
link |
And you can imagine sometimes it might be a little trickier
link |
although there have been leg boxes
link |
that have been developed and arranged for this purpose.
link |
And what was remarkable
link |
is that they could finish these experiments
link |
and have the patient, the person,
link |
enter a state of relaxation,
link |
reduce the pain in the phantom limb,
link |
and it would stay there
link |
even though of course, as they exited the mirror box,
link |
they would go about their life
link |
and use their intact limb for its various purposes.
link |
I love this experiment because it really speaks
link |
to the subjective nature of pain and pleasure.
link |
It speaks to the power of the visual system.
link |
just like the nail through the boot experiment,
link |
what we see profoundly impacts our experience
link |
of pleasure and pain, in this case, pain.
link |
Now there's another aspect to the phantom limb experience
link |
and of these maps,
link |
the so-called homunculus maps in the cortex
link |
that Ramachandran worked on,
link |
which is very interesting
link |
and reveals the degree to which these maps are plastic
link |
or can change in response to experience.
link |
Turns out that because of the locations
link |
of different body part representations within these maps,
link |
certain parts of our body
link |
that normally we don't think of as related
link |
can start to create merged experiences.
link |
What do I mean by that?
link |
Well, Ramachandran described a patient
link |
who had a somewhat odd experience
link |
of having lost their foot.
link |
So they actually had their foot amputated
link |
about midway up the Achilles,
link |
so lower portion of the calf and foot.
link |
I don't recall what the reason was for having it removed.
link |
And fortunately for this patient,
link |
they did not experience pain in that portion of their body,
link |
but rather they confided in him
link |
that whenever they would have sex,
link |
they would experience their orgasm in their phantom foot
link |
in addition to in their genitals, of course.
link |
And Ramachandran understood the homunculus map
link |
and he understood that this was because
link |
the representation of the foot within the homunculus
link |
actually lies adjacent to
link |
and is somewhat interdigitated with,
link |
it actually kind of merges with
link |
the representation of the genitalia.
link |
Now, that's a weird situation.
link |
And yet you now know that the density of innervation
link |
of the feet and the genitalia,
link |
as well as the lips and the face
link |
are actually the highest sensory innervation
link |
that you have in your entire body.
link |
And this speaks to, I think,
link |
a more important general principle for all people
link |
of the experience of pleasure or pain,
link |
which is that an aspect of our pain or pleasure
link |
can be highly localized, right?
link |
It can be because of a cut
link |
to a particular location on the body,
link |
or it can be because, excuse me,
link |
of a fall injury or a kind of bruise
link |
on one side of our body.
link |
And yet our experience of pleasure and pain
link |
can also be an almost body-wide experience.
link |
And yet it's always most rich,
link |
it's always most heightened in these regions of our body
link |
that have dense sensory innervation.
link |
So we experience pain and pleasure
link |
according to local phenomenon receptors in the skin
link |
and this homunculus map that has all these
link |
different territories.
link |
But because of the way that those territories are related,
link |
this kind of wild example of somebody experiencing orgasm
link |
in their phantom foot speaks to the larger experience,
link |
the more typical, rather, experience that I should say,
link |
that all people have,
link |
which is that pleasure can be body-wide,
link |
or we can experience it in our face,
link |
the bottoms of our feet and other areas of the body
link |
that we experience pleasure, and similarly with pain.
link |
And that brings us to the topic of whole body pain,
link |
not just localized pain, as well as whole body pleasure,
link |
not just localized pleasure.
link |
There are a number of examples of whole body pain
link |
that people suffer from.
link |
And one common one is called fibromyalgia.
link |
I want to just first share with you
link |
a little bit of medical insight.
link |
A few months back, I did an Instagram Live
link |
with Dr. Sean Mackey, who's an MD, medical doctor,
link |
and a PhD at Stanford School of Medicine.
link |
That was recorded and placed on my Instagram.
link |
If you want to check it out,
link |
we can provide a link to that in the show notes.
link |
Dr. Mackey is the chief of the division of pain
link |
at Stanford School of Medicine.
link |
So he's a scientist, he studies pain,
link |
and he treats patients dealing with various forms of pain,
link |
whole body pain like fibromyalgia, acute pain, et cetera.
link |
And he shared with me something very interesting,
link |
which is that anytime you hear or see the word syndrome,
link |
that means that the medical establishment
link |
does not understand what's going on.
link |
A syndrome is a constellation of symptoms
link |
that point in a particular direction
link |
or some general set of directions
link |
about what could be going on,
link |
but it doesn't reveal a true underlying disease necessarily.
link |
It could be a aggregate of diseases,
link |
or it could be something else entirely.
link |
And I want to make sure that I emphasize
link |
the so-called psychosomatic phenomenon.
link |
I think sometimes we hear psychosomatic
link |
and we interpret that as meaning all in one's head,
link |
but I think it's important to remember
link |
that everything is neural,
link |
whether or not it's pain in your body
link |
because you have a gaping wound
link |
and you're hemorrhaging out of that wound,
link |
or whether or not it's pain for which you cannot explain it
link |
on the basis of any kind of injury, it's all neural.
link |
So saying body, brain, or psychosomatic,
link |
it's kind of irrelevant,
link |
and I hope someday we move past that language.
link |
Psychosomatic is interesting.
link |
There was a paper that was published in 2015,
link |
and then again in 2020, a different paper
link |
focused on the so-called psychogenic fevers
link |
or psychosomatic effects.
link |
And I just briefly want to mention this
link |
because it relates back to pain.
link |
These studies have shown that there are areas
link |
of the so-called thalamus,
link |
which integrates and filters sensory information
link |
of different kinds.
link |
And within the brainstem, an area called the DMH,
link |
and I can also provide a link to this study if you like,
link |
that shows that there is a true neurological basis.
link |
There are brain areas and circuits
link |
that are related to what's called psychogenic fever.
link |
When we are stressed, and in particular,
link |
if we think that we were injured
link |
or that we were infected by something,
link |
we can actually generate a true fever.
link |
It is not an imagined fever,
link |
it is our thinking generating an increase
link |
in body temperature.
link |
And so this has been called psychosomatic,
link |
it's been called psychogenic,
link |
but it has a neural basis, okay?
link |
So when we hear syndrome,
link |
and a patient comes into a clinic
link |
and says that they suffer, for instance,
link |
from something which is very controversial, frankly,
link |
like chronic fatigue syndrome,
link |
some physicians believe that it reflects
link |
a real underlying medical condition, others don't.
link |
However, syndrome means we don't understand.
link |
And that doesn't mean something doesn't exist.
link |
Fibromyalgia or whole body pain for a long time
link |
was written off or kind of explained away
link |
by physicians and scientists, frankly,
link |
my community, as one of these syndromes.
link |
It couldn't be explained.
link |
However, now there is what I would consider,
link |
and I think others would and should consider,
link |
firm understanding of at least one of the bases
link |
for this whole body pain.
link |
And that's activation of a particular cell type
link |
And there's a receptor on these glia,
link |
for those of you that want to know,
link |
called the TOLE4 receptor.
link |
And activation of the TOLE4 receptor
link |
is related to certain forms of whole body pain
link |
Now, what treatments exist for fibromyalgia?
link |
And even if you don't suffer from fibromyalgia,
link |
and even if you don't know anyone who does,
link |
this is important information
link |
because what I'm about to tell you
link |
relates to how you and your body,
link |
which is you of course,
link |
can deal with pain of any kind.
link |
And there are actually things that one can do and take
link |
that can encourage nerve health in general,
link |
in other conditions like diabetic neuropathy,
link |
but in all individuals.
link |
So there are clinical data using a prescription drug.
link |
This is work that actually was done
link |
by Dr. Mackey and colleagues.
link |
The drug is called naltrexone.
link |
Naltrexone is actually used for the treatment
link |
of various opioid addictions and things of that sort.
link |
But it turns out that a very low dose,
link |
I believe it was a 1 10th the size of the typical dose
link |
of naltrexone, has been shown to have some success
link |
in dealing with and treating certain forms of fibromyalgia.
link |
And it has that success because of its ability
link |
to bind to and block these toll-4 receptors on glia.
link |
So this so-called syndrome,
link |
or this thing that previously was called a syndrome,
link |
fibromyalgia, actually has a biological basis.
link |
It was not just in patients' heads.
link |
And I really tip my hat to the medical establishment,
link |
including Dr. Mackey and others,
link |
who explored the potential underlying biologies
link |
of things like fibromyalgia
link |
and are starting to arrive at treatments.
link |
Now, I'm not a physician, I'm a professor,
link |
so I'm not prescribing anything.
link |
You should talk to your doctor, of course,
link |
if you have fibromyalgia or other forms of chronic
link |
or whole body pain to explore whether or not
link |
these low dose naltrexone treatments are right for you.
link |
But I think it's a beautiful case study, if you will,
link |
not a case study of an individual patient,
link |
but a case in study of linking up the patient's self-report
link |
of these experiences and using science
link |
to trying to establish clinical treatments.
link |
There's another treatment,
link |
or I should say there's another approach
link |
that one could take.
link |
And again, I'm not recommending people do this necessarily.
link |
You have to determine what's right and safe for you.
link |
Your situation's very far too much,
link |
and it would be outside of my wheelhouse
link |
to prescribe anything.
link |
But there's a particular compound,
link |
which in the United States is sold over the counter,
link |
and in Europe is prescription.
link |
It's one that I've talked about on this podcast before
link |
for other purposes.
link |
And that compound is acetyl L-carnitine.
link |
Acetyl L-carnitine, as I mentioned,
link |
is by prescription in most countries in Europe.
link |
In the US, you can buy this over the counter.
link |
There is evidence that acetyl L-carnitine
link |
can reduce the symptoms of chronic whole body pain
link |
and other certain forms of acute pain
link |
at dosages of somewhere between one to three
link |
and sometimes four grams per day.
link |
Now, acetyl L-carnitine can be taken orally.
link |
It's found in 500 milligram capsules,
link |
as well as by injection.
link |
By injection in the States, in the United States that is,
link |
also requires a prescription,
link |
or requires a prescription, I should say.
link |
The over the counter forms are generally capsules
link |
Those apparently do not require a prescription.
link |
There are several studies exploring acetyl L-carnitine
link |
in this context, as well as for diabetic neuropathy.
link |
And what's interesting about acetyl L-carnitine
link |
is it's one of the few compounds
link |
that isn't just used for the treatment of pain,
link |
but has also been shown in certain contexts
link |
to improve peripheral nerve health generally.
link |
And for that reason, it's an interesting compound.
link |
I've also talked about acetyl L-carnitine
link |
on here previously because it has robust effects
link |
on things like sperm motility and health,
link |
including the speeds at which sperm swim,
link |
how straight they swim.
link |
Turns out that swimming for sperm is more efficient
link |
if they swim straight,
link |
as opposed to like those kids on the swim team
link |
that are like banging up against the lane lines
link |
and zigzagging all over the place.
link |
So it does turn out to be the case that the quickest route
link |
between any two places is a straight line.
link |
And the good sperm know that,
link |
and the less good sperm don't seem to know that.
link |
And acetyl L-carnitine seems to facilitate
link |
straight swimming trajectories,
link |
as well as speed of swimming and overall sperm health.
link |
And there is evidence from quality peer-reviewed studies
link |
showing that acetyl L-carnitine supplementation
link |
can also be beneficial for women's fertility
link |
in ways that it affects perhaps,
link |
we don't really know the mechanism,
link |
health and status of the egg or egg implantation.
link |
There are a large number of studies on acetyl L-carnitine.
link |
You can look those up on PubMed if you like,
link |
or on examine.com.
link |
There are some studies that I don't think are included there
link |
which are particularly interesting.
link |
One that I just would like to reference the last,
link |
the last name of the first author is Mahdavi.
link |
The title of the paper is effects of L-carnitine
link |
supplementation on serum inflammatory markers
link |
and matrix metalloprotease enzymes
link |
in females with knee osteoarthritis.
link |
So this is a randomized double-blind
link |
placebo controlled pilot study
link |
that showed really interesting effects
link |
of short-term supplementation of acetyl L-carnitine.
link |
Longer term, the effects were less impressive.
link |
So it's pretty interesting that this compound
link |
has so many different effects.
link |
How could it have these effects?
link |
Well, it appears that it's having these effects
link |
through its impact on the so-called inflammatory cytokines.
link |
Inflammatory cytokines for those of you that don't know
link |
are secreted by the immune system
link |
in response to different stressors,
link |
physical stressors, mental stressors too,
link |
food that you eat that isn't good for you.
link |
The so-called hidden sugars,
link |
yes, will increase inflammation
link |
if they're ingested too often
link |
or in amounts that are too high in quantity.
link |
Things like interleukin-1 beta,
link |
things like C-reactive protein,
link |
things like interleukin-6.
link |
Interleukin-6 is kind of the generic inflammatory marker
link |
that all studies refer to.
link |
And yet there are other interleukins,
link |
please note that there are other interleukins
link |
like interleukin-10 that are anti-inflammatory.
link |
So your immune system can secrete inflammatory molecules
link |
to deal with wounds and stress and things.
link |
And in the short term, that's good.
link |
And in the long term, that's bad.
link |
And it can secrete anti-inflammatory cytokines like IL-10.
link |
And these matrix metalloproteases, it's kind of a mouthful,
link |
but these matrix metalloproteases are very interesting.
link |
Anytime you see ACE, that's generally an enzyme,
link |
which means that these compounds in this case,
link |
these matrix metalloproteases
link |
are used to break down certain elements around wounds
link |
and scarring, which might sound like a bad thing,
link |
but in some cases is good because it allows certain cells,
link |
like glial cells, so-called microglia,
link |
to come in like little ambulances,
link |
like little paramedics and clean up wounds.
link |
So scarring and inflammation is kind of a double-edged sword.
link |
It can be good, but too much scarring,
link |
if it contains a wound too much,
link |
doesn't allow the infiltration of cell types
link |
to move in and take care of that wound and heal it up.
link |
So it appears that L-carnitine is impacting
link |
a number of different processes, both to impact pain
link |
and perhaps, and I want to underscore perhaps,
link |
but there are good studies happening now,
link |
perhaps accelerate wound healing as well.
link |
As long as we're talking about acute pain and chronic pain
link |
and supplementation and non-prescription drugs,
link |
at least in the United States,
link |
that people can take to deal with pain of various kinds.
link |
I'd be remiss if I didn't mention the two
link |
that I get asked most often about, which are agmatine
link |
and S-adenosylmethionine, which is sometimes called SAMe.
link |
Both of those have been shown to have some impact,
link |
categorized on examine as notable impact
link |
on various forms of pain due to osteoarthritis
link |
or due to injury of various kinds
link |
in different subject population,
link |
men, women, people of different ages, et cetera.
link |
SAMe in particular has been interesting
link |
because it's been shown head to head with drugs
link |
like naproxen and other drugs of that sort,
link |
which are well established and sold over the counter
link |
in the US to work at least as well
link |
as some of those compounds at certain dosages.
link |
But it's also been shown that SAMe
link |
and some of those things take more time
link |
in order to have those effects.
link |
In fact, head to head with things like naproxen
link |
have been shown that they can take up to a month
link |
in order to have the pain relieving effect.
link |
Now, whether or not that makes them a better choice
link |
or a worse choice really depends on your circumstances.
link |
I'm certainly not recommending that anybody take anything,
link |
but I do think it's interesting and important
link |
to point out that things like agmatine,
link |
things like SAMe have been shown
link |
under certain circumstances to be beneficial for pain.
link |
And they are outside the realm of prescription drugs.
link |
And I think this is a growing area of,
link |
some people call them supplements,
link |
some people call them nutraceuticals.
link |
Look, at the end of the day,
link |
these are compounds that affect cellular processes
link |
and the more that we understand
link |
how they affect those cellular processes,
link |
as we now do for things like acetyl-L-carnitine,
link |
I think the more trust that we can put into them
link |
or the more to which we might want to avoid them
link |
because of some of the side effects or contraindications
link |
that those compounds could have.
link |
If you're interested in those other compounds,
link |
I do invite you, as I always do, to check out examine.com,
link |
but also to do your research on those compounds
link |
by simply putting them into Google
link |
or putting them into PubMed, which would be even better.
link |
And if you are going to go into PubMed,
link |
if you're going to start playing scientists,
link |
which I do encourage you to do,
link |
I would encourage you to not just read abstracts,
link |
but if you can, if the studies are freely available,
link |
I realize not all of them are freely available,
link |
to try and read those studies,
link |
at least to the extent that you can.
link |
There's a particularly nice study that you might look at
link |
that was published in 2010 in Pain Medicine,
link |
which is K-Nan et al, K-E-Y-N-A-N,
link |
which looked at the safety and efficacy
link |
of dietary-agmentine sulfate
link |
on lumbar disc-associated radiculopathy.
link |
I'm not laughing at the condition.
link |
It's a painful condition that describes,
link |
it's kind of a range of symptoms
link |
that relate to pinching of nerves.
link |
The spinal columns, I was laughing at my pronunciation of it.
link |
That particular study is quite good.
link |
And the conclusion of that study that they drew
link |
was that there were limited side effects
link |
and that dietary-agmentine sulfate
link |
is safe and efficacious for treating and alleviating pain
link |
and improving quality of life
link |
in lumbar disc-associated pain.
link |
However, there were very specific dosage regimens,
link |
excuse me, that were described there
link |
and duration of treatment.
link |
And so you should not take anything that I say
link |
or that study to mean that you can just take this stuff
link |
willy-nilly or at any concentration, of course, or dose.
link |
You always want to pay attention to what the science says.
link |
That paper, fortunately, is freely available online
link |
and we will also provide a link to that study.
link |
For those of you that are interested in SAMe
link |
and its usage for the treatment of various types of pain
link |
and perhaps other benefits,
link |
a number of companies have stopped making SAMe.
link |
Instead, what they're now focusing on
link |
is what they think is a better or more bioavailable
link |
alternative, which is 5-methyl tetrahydrofolate
link |
This molecule is necessary for converting homocysteine
link |
to methionine, which is then converted to SAMe.
link |
So rather than taking SAMe directly,
link |
the idea is to take something that's upstream of SAMe
link |
and make more SAMe endogenously available.
link |
This is a different strategy.
link |
I've talked about this strategy before
link |
for increasing other things like growth hormone, et cetera.
link |
There's always this question of whether or not
link |
in trying to increase the amount of a particular molecule
link |
in the body, whether or not taking that specific molecule
link |
is the best thing or working further upstream
link |
as it's referred to, working on the precursor
link |
or increasing the levels of the precursor
link |
is the better way to go.
link |
It appears that this 5-MTHF is the strategy
link |
that people are now taking in place of taking SAMe directly.
link |
So in other words, they're taking this
link |
in order to get elevated levels of SAMe.
link |
Now I'd like to turn our attention to a completely non-drug,
link |
non-supplement related approach to dealing with pain.
link |
And it's one that has existed for thousands of years.
link |
And that only recently has the Western scientific community
link |
started to pay serious attention to,
link |
but they have started to pay serious attention to it.
link |
And there is terrific mechanistic science
link |
to now explain how and why acupuncture can work very well
link |
for the treatment of certain forms of pain.
link |
Now, first off, I want to tell you what was told to me
link |
by our director or chief of the pain division
link |
at Stanford School of Medicine, Dr. Sean Mackey,
link |
which was that some people respond very well to acupuncture
link |
and others do not.
link |
And the challenge is identifying who will respond well
link |
and who won't respond well.
link |
Now, when I say won't respond well,
link |
that doesn't necessarily mean that they responded
link |
in a negative way, that it was bad for them.
link |
But it does appear that a fraction of people
link |
experience tremendous pain relief from acupuncture
link |
and others experience none at all or very little
link |
to the point where they have to seek out
link |
other forms of treatment.
link |
The science on this is still ongoing.
link |
There was actually an excellent paper published on this
link |
in the Journal of the American Medical Association,
link |
one of the premier medical clinical journals.
link |
And it basically reinforced the idea
link |
that you have responders and non-responders.
link |
A number of laboratories have started to explore
link |
how acupuncture works.
link |
And one of the premier laboratories for this
link |
is Chufu Ma's lab at Harvard Medical School.
link |
Chufu has spent many years studying the pain system
link |
and a system that's related to the pain system,
link |
which is the system that controls our sensation
link |
Just as a brief aside about itch,
link |
itch and pain are often co-associated with one another.
link |
I was recently in Texas and I will tell you,
link |
they have some mean mosquitoes.
link |
They're small, but whatever they're injecting
link |
into your skin, well, here I am talking now
link |
about my subjective experience of pain.
link |
Whatever they injected into my skin felt to me
link |
like the most extreme mosquito bites I've ever had.
link |
Not while they were biting me,
link |
not while they were injecting the venom,
link |
but boy, do those Texan mosquitoes make me itch.
link |
How do they do it?
link |
Well, their venom creates little packets
link |
of so-called histamine that travel around.
link |
Those packets are called mast cells,
link |
little packets of histamine that go to that location
link |
and make me, and presumably you,
link |
want to scratch those mosquito bites.
link |
I scratch mine, you scratch yours,
link |
but we both scratch our mosquito bites.
link |
And when we do that, the histamines are released,
link |
it gets red and inflamed, and they itch even worse.
link |
The inflammation is actually caused by the histamine.
link |
Well, that experience of inflammation and pain and itch
link |
is what we call a pre-rogenic experience, okay?
link |
So we have pain, which is nociception, essentially.
link |
I know that the pain aficionados always get a little upset
link |
because they say, oh, there's no such thing
link |
as a pain receptor.
link |
It's nociceptive receptors,
link |
and pain is subjective experience.
link |
Yes, I acknowledge all that, but for fluency,
link |
let's just think about pain as a certain experience
link |
and itch as a separate experience,
link |
but they often exist together because those mosquito bites
link |
were what I would call painful, or at least not pleasant.
link |
They didn't just itch, they were also painful,
link |
and that's because itch brings with it inflammation,
link |
and inflammation often brings with it pain relief,
link |
but it can also bring with it the sensation of pain.
link |
So itch and pain are two separate phenomenon.
link |
It was actually discovered
link |
through a really interesting phenomenon
link |
that relates to something that is actually consumed
link |
in supplement form, which is this tropical legume.
link |
It's actually a bean called mucuna purines.
link |
That's M-U-C-U-N-A, that's one word.
link |
P-R-U-I-E-N-S, mucuna purines is a bean.
link |
It's this legume that this bean is 99% L-DOPA.
link |
It's dopamine, or rather it's the precursor to dopamine,
link |
and people buy this stuff and take it over the counter
link |
as ways to increase their levels of dopamine.
link |
It does make you feel really dopamine doubt.
link |
I mean, it makes you feel a little high
link |
and really motivated and really energetic,
link |
a lot like other drugs that will do that.
link |
I don't necessarily recommend taking mucuna purines.
link |
I personally don't like taking it.
link |
It doesn't make me feel good.
link |
I crash really hard when I take it.
link |
But on the outside of this bean
link |
is a compound that makes people itch, okay?
link |
So they remove this when you take it in supplement form.
link |
In fact, it's usually in capsule form.
link |
But the outside of this bean is like a hairy bean, right?
link |
And those little hairs contain a compound
link |
which was actually used to study
link |
and identify these itch receptors in the skin.
link |
So we don't have time to go into all the details of itch,
link |
but it's pretty interesting
link |
that you have these compounds out in nature
link |
that can make us itch.
link |
Inside them, they have dopamine.
link |
I mean, this is really weird,
link |
but plant compounds are really powerful.
link |
So don't let anyone tell you
link |
that because something's from a plant or an herb,
link |
that it's not powerful.
link |
There are very powerful plant and herb compounds,
link |
mucuna purines being one of them
link |
with dopamine on the inside and itchy stuff on the outside.
link |
Now, what does this all have to do with acupuncture?
link |
Well, Chufu Ma's lab
link |
has not just identified the itch pathway,
link |
these puridogens as they're called, which cause itch,
link |
and the purigenic phenomenon
link |
of itch being separate from pain.
link |
His lab has also studied how acupuncture causes relief of,
link |
but also can exacerbate pain.
link |
Now, the form of acupuncture that they explored
link |
was one that's commonly in use called electroacupuncture.
link |
So this isn't just putting little needles
link |
into different parts of the body.
link |
These needles are able to pass an electrical current,
link |
not magically, but because they have a little wire
link |
going back to a device and you can pass electrical current.
link |
Here's what they found.
link |
There's a public, this is a study, excuse me,
link |
published in the journal Neuron, Cell Press Journal,
link |
excellent journal, very high stringency.
link |
So what Chufu Ma's lab found
link |
was that if electroacupuncture
link |
is provided to the abdomen, to the stomach area,
link |
it creates activation
link |
of what are called the sympathetic ganglia.
link |
These have nothing to do with sympathy in the emotional sense
link |
has to do with the stress response.
link |
Sympa just means together.
link |
So it activated a bunch of neurons along the spinal cord
link |
and the activation of these neurons involves noradrenaline
link |
and something called NPY, neuropeptide Y.
link |
The long and short of it is that stimulating the abdomen
link |
with electroacupuncture was either anti-inflammatory
link |
or it could cause inflammation.
link |
It could actually exacerbate inflammation
link |
depending on whether or not it was of low or high intensity.
link |
Now that makes it a very precarious technique.
link |
And this may speak to some of the reason
link |
why some people report relief from acupuncture
link |
and others do not.
link |
However, they went a step further
link |
and stimulated other areas of the body
link |
using electroacupuncture.
link |
And what they found is that stimulation of the legs,
link |
of the hind limbs as it's called in animals
link |
and the legs in humans caused a circuit,
link |
a neural circuit to be activated that goes from the legs
link |
up to an area of the base of the brain called the DMV,
link |
not the DMH, which I mentioned earlier,
link |
but the DMV, like you go to the DMV,
link |
which is a miserable experience for most people,
link |
forgive me, DMV employees, but let's be honest,
link |
most people don't enjoy going to the DMV as patrons,
link |
but we have to, so we go.
link |
The DMV and low intensity stimulation,
link |
this electroacupuncture of the hind limbs activated the DMV
link |
and activated the adrenal glands,
link |
which sit atop your kidneys and cause the release
link |
of what are called catecholamines.
link |
And those were strongly anti-inflammatory.
link |
In other words, electroacupuncture of the legs and feet
link |
can if done correctly be anti-inflammatory
link |
and reduce symptoms of pain.
link |
And can we think accelerate wound healing
link |
because activations of these catecholaminergic pathways
link |
can accelerate wound healing as well.
link |
So the takeaway from this is that while there are thousands
link |
of years and millions of subjects involved in explorations
link |
of electroacupuncture and acupuncture,
link |
Western medicine is starting to come into this
link |
and start to explore underlying mechanism.
link |
Now, for those of you that love acupuncture
link |
and are real proponents of it, it's worked for you.
link |
You might say, well, why does Western medicine
link |
even need to come into this?
link |
Why should they even be exploring this?
link |
But we should all be relieved that they are
link |
because what's starting to happen now
link |
is that as the mechanistic basis for this
link |
is starting to come to light,
link |
insurance coverage of things like acupuncture
link |
is starting to emerge as well.
link |
And this is in contrast to other therapies
link |
for which there's a lot of anecdotal evidence
link |
but very little mechanistic understanding.
link |
One example of that would be laser photobiomodulation,
link |
the use of lasers of different types really
link |
to treat pain and to accelerate wound healing.
link |
A lot of people claim that this can really help them.
link |
However, most places, at least in the States,
link |
won't cover this with insurance
link |
or don't perform this in standard clinics.
link |
And the reason is the underlying mechanism isn't known.
link |
I'm not going to get into the argument
link |
about whether or not mechanistic understanding
link |
should or should not be required
link |
in order to have insurance coverage of things that work.
link |
That's not what this is about.
link |
And that actually would be a boring discussion
link |
because I'm shouting in a tunnel through you
link |
and I wouldn't be able to hear you shout back
link |
no matter what your stance on that is.
link |
But just trust me when I say that I am both relieved
link |
and delighted to hear that excellent medical institutions
link |
like Stanford are starting to think about
link |
electro-acupuncture and how it can work,
link |
that places like Harvard Medical School
link |
are starting to explore this at a mechanistic level.
link |
And I do believe that there's an open-mindedness
link |
that's starting to emerge.
link |
For instance, the National Institutes of Health
link |
not only has an Institute for Mental Health
link |
and Cancer Research and an Eye Institute,
link |
but now Complementary Health, the so-called NCCIH,
link |
National Institutes of Complementary Health,
link |
that is exploring things like electro-acupuncture,
link |
meditation, various supplements and things of those sort.
link |
I do think that we're entering a new realm
link |
in which things like pain and pain management
link |
will be met with more openness by all physicians.
link |
At least that's my hope.
link |
So please take that into consideration.
link |
Right now, the mechanistic evidence
link |
for laser photobiomodulation is not strong.
link |
One of the major issues or the barriers to that
link |
is that most of the studies that are out there
link |
were actually paid for by companies
link |
that build devices for laser photobiomodulation.
link |
And so we really need independent studies
link |
funded by federal institutions that have no bias
link |
or financial relationship in order to gain trust
link |
in whatever data happened to emerge.
link |
There is a technique that at one time
link |
was considered alternative,
link |
but now has a lot of mechanistic science
link |
to explain how it works.
link |
And it does indeed work for the treatment of chronic
link |
and also for acute pain.
link |
And that treatment is hypnosis, in particular, self-hypnosis.
link |
Now, my colleague at Stanford, in fact, my collaborator,
link |
Dr. David Spiegel, our associate chair of psychiatry,
link |
has devoted his professional life
link |
to developing hypnosis tools that people can use
link |
to help them sleep better, focus better,
link |
stay motivated, et cetera.
link |
While most people hear hypnosis and they think,
link |
oh, this is staged hypnosis,
link |
people walking around like chickens
link |
or being forced to laugh or fall asleep on command, et cetera,
link |
this is completely different than all that.
link |
This is self-hypnosis.
link |
And there are now dozens, if not more,
link |
quality peer-reviewed studies
link |
published in excellent journals
link |
done by Dr. Spiegel and others at other universities.
link |
It really all has to do with how self-hypnosis
link |
can modulate activity of the prefrontal cortex
link |
and related structures like the insula.
link |
The prefrontal cortex is involved
link |
in our executive function, as it's called,
link |
our planning, our decision-making,
link |
but also how we interpret context,
link |
what the meaning of a given sensation is.
link |
And that's extremely powerful.
link |
Just want to remind everybody
link |
that the currency of the brain and body
link |
has not changed in hundreds of thousands of years.
link |
It's always been dopamine, serotonin, glutamate, GABA,
link |
testosterone, estrogen.
link |
What's changed are the contingencies,
link |
the events in the world that drive
link |
whether or not we get an increase or decrease
link |
in testosterone or estrogen,
link |
the events in the world that dictate
link |
whether or not we get an increase or a decrease in dopamine.
link |
Believe me, the events that drove those increases
link |
and decreases were very different,
link |
even a hundred years ago than they are now.
link |
And as we create new things and societies change, et cetera,
link |
they will continue to exchange information
link |
in the same currency, which is dopamine, serotonin,
link |
and all these other neuromodulators and chemicals.
link |
Hypnosis takes advantage of this
link |
by allowing an individual, you if you like,
link |
to change the way that you interpret particular events
link |
and to actually experience what would be painful
link |
as less painful or not painful.
link |
And that's just the example of pain.
link |
Hypnosis is powerful for other reasons too.
link |
It actually can help rewire neural circuits
link |
so that you don't experience as much pain
link |
so that you can sleep faster, focus faster.
link |
If this is all sounding very fantastical,
link |
well, it's supported by data.
link |
The data are that when people do self-hypnosis,
link |
even brief self-hypnosis of 10 or 15 minutes
link |
a few times a week, maybe even return to that hypnosis
link |
by just using a one minute a day hypnosis,
link |
they can achieve significant and often very impressive
link |
degrees of pain relief and chronic pain,
link |
whether or not that chronic pain arises
link |
through things like fibromyalgia or through other sources.
link |
If you want to check this out,
link |
there's a wonderful zero cost resource
link |
that's grounded in this work.
link |
It's the app, reveri.com.
link |
So R-E-V-E-R-I.com.
link |
There you can download a zero cost app for Apple phones
link |
or for Android phones.
link |
And there are a variety of different hypnosis scripts.
link |
These are actually self-hypnosis scripts,
link |
and you'll actually hear Dr. David Spiegel talking to you.
link |
He can teach you about hypnosis and how it works.
link |
There are links to scientific studies
link |
at that web address that I gave you before, reveri.com.
link |
You can see the various studies and the various writeups
link |
related to those studies and how this all works.
link |
And they're simple protocols.
link |
You just click on a tab and you listen
link |
to the self-hypnosis and it will take you into hypnosis.
link |
And several of those hypnosis scripts
link |
have been shown clinically
link |
to relieve certain patterns of chronic pain.
link |
So it's a powerful tool.
link |
And I encourage you not to write off the non-drug,
link |
non-supplement tools as less than powerful,
link |
because indeed many people experience
link |
tremendous relief from them.
link |
And of course they also can be combined
link |
with drug treatments, if that's right for you,
link |
or with supplements and things of that sort to treat pain,
link |
if that's right for you.
link |
So again, electroacupuncture,
link |
now often supported by insurance, not always, but often,
link |
great mechanistic data starting to emerge.
link |
Hypnosis, terrific tool.
link |
There's even the self-hypnosis tool
link |
that one can access through the zero-cost app, Reverie,
link |
and lots of great clinical data
link |
and scientific mechanistic data.
link |
There are neuroimaging studies
link |
showing the different brain areas are activated in hypnosis,
link |
the so-called default network,
link |
kind of where your brain kind of idols
link |
and the different circuits that are active at rest
link |
shift with hypnosis and shift long-term
link |
in ways that positively conserve you.
link |
And then these things like laser photobiomodulation,
link |
still more or less in that experimental medical community,
link |
I should say Western medical community, not so certain,
link |
but hopefully there will be data soon.
link |
And hopefully those data will point to mechanisms
link |
that allow the insurance companies
link |
and other sort of medical bodies to support them
link |
if indeed they have a mechanistic basis.
link |
I just want to briefly touch on a common method
link |
of pain relief that speaks to a more general principle
link |
of how things like electroacupuncture
link |
and also some of these new emerging techniques
link |
of kind of like active tissue release
link |
and this principle that you hear a lot about
link |
in sports medicine now,
link |
that when you have pain or injury at one site,
link |
that you should provide pressure above and below that site.
link |
You may have seen this in the Olympics,
link |
which is ongoing now,
link |
where people will put tape on their body
link |
at certain locations.
link |
Oftentimes the logic or what they're saying
link |
is that this is designed to create relief in a joint
link |
or in a limb that's below the tape,
link |
not necessarily under the tape, but above or below.
link |
So for instance, if there's pain in one shoulder,
link |
sometimes they will put it on the trapezius muscle
link |
or things of that sort.
link |
It turns out that there is a basis for this
link |
because of the way that these different nerves
link |
run in from the skin and from the muscles
link |
up into the spinal cord and into the brainstem,
link |
providing pressure on one nerve pathway
link |
can often impact another pathway.
link |
And the simplest and most common example of this
link |
is one that we all do instinctually or intuitively,
link |
even animals do this.
link |
This is something that in the textbooks
link |
is called the gait theory of pain
link |
developed by Melzack and Wall, kind of classic theory.
link |
Basically we have receptors in our skin,
link |
the so-called C-fibers.
link |
That's just a name for these little wires
link |
that come from a particular class of DRGs
link |
that's very thin that brings about certain kinds
link |
of nociceptor information.
link |
I want to say pain information, but then the pain people,
link |
believe it or not, they're pain people.
link |
Sometimes they're a pain because what they tell me
link |
is there aren't pain receptors, okay, nociceptors.
link |
That information comes in through the C-fibers
link |
and what happens when we injure something?
link |
Well, provided that we won't damage it worse by touching it,
link |
oftentimes what we will do is we will rub the source of pain
link |
or the location in which we were experiencing pain.
link |
And it turns out that's not an unuseful thing to do.
link |
When we rub our skin or an area
link |
or we provide pressure nearby it,
link |
we activate the so-called A-fibers,
link |
the bigger wires and neurons that innervate,
link |
meaning they jut into that area of skin.
link |
And those A-fibers,
link |
the ones that respond to mechanical pressure,
link |
actually are able to inhibit those C-fibers,
link |
the ones that are carrying that so-called pain information.
link |
So rubbing an area or providing pressure above
link |
or below an injury actually provides
link |
real pain relief support for the location of that injury
link |
or that pain because of the way
link |
that these different patterns
link |
or these different types of neurons
link |
interact with one another.
link |
When I say it inhibits it,
link |
I don't mean that it like shouts at it.
link |
What it does is it releases,
link |
it's literally kind of like vomits up
link |
a little bit of a neurotransmitter called GABA.
link |
And GABA is a neurotransmitter that inhibits,
link |
it quiets the activity of other neurons.
link |
And so it's acting as kind of an analgesic, if you will.
link |
It's acting as its own form of drug
link |
that you make with your body to quiet the activity
link |
of these pain neurons.
link |
So rubbing a wound,
link |
provided it doesn't damage the wound worse,
link |
or providing pressure above or below,
link |
typically it's above a particular injury,
link |
can have a real effect in relieving
link |
some of the pain of that injury.
link |
And some people have speculated this is through fascia
link |
or this is through other bodily organs and tissues.
link |
And it might be, we're going to do a whole episode on fascia.
link |
It's extremely interesting tissue.
link |
But right now it seems that the main source
link |
of that pain relief is through this A-fiber inhibition
link |
of these C-fibers,
link |
so-called Melzack and Wahl gate theory of pain,
link |
if you'd like to look it up and learn about that further.
link |
Now let's talk about a phenomenon that has long intrigued
link |
and perplexed people for probably thousands of years,
link |
and that's redheads.
link |
You may have heard before
link |
that redheads have a higher pain threshold
link |
than other individuals.
link |
And indeed that is true.
link |
There's now a study that looked at this mechanistically.
link |
There's a gene called the MC1R gene.
link |
And this MC1R gene encodes
link |
for a number of different proteins.
link |
Some of those proteins, of course,
link |
are related to the production of melanin.
link |
This is why redheads often, not always,
link |
but often are very fair-skinned,
link |
sometimes have freckles, not always,
link |
and of course have red hair.
link |
Some people are really intense gingers,
link |
not psychologically or emotionally intense,
link |
but meaning their hair is very, very red.
link |
Others, it's a lighter red.
link |
So of course there's variation here.
link |
But this gene, this MC1R gene,
link |
is associated with a pathway
link |
that relates to something that I've talked about
link |
on this podcast before
link |
during the episode on hunger and feeding.
link |
POMC stands for pro-opio-melanocortin.
link |
And POMC is cut up.
link |
It's cleaved into different hormones,
link |
including one that enhances pain perception.
link |
This is melanocyte-stimulating hormone.
link |
And another one that blocks pain, beta-endorphin.
link |
Now, if you listen to the episodes
link |
on testosterone and estrogen
link |
and the episodes on hunger and feeding,
link |
some of these molecules will start to ring a bell.
link |
Things like melanostimulating hormone
link |
relate to pigmentation in the skin,
link |
relate to sexual arousal, et cetera.
link |
But it turns out that in redheads,
link |
because of the fact that they have this gene,
link |
the POMC, pro-opio-melanocortin,
link |
that's cut into different hormones,
link |
melanocyte-stimulating hormone,
link |
and another one, beta-endorphin.
link |
Beta-endorphin should cue you to the fact
link |
that this is in the pain pathway.
link |
The endorphins are endogenously made,
link |
meaning made within our body, opioids.
link |
They actually make us feel numb
link |
in response to certain kinds of pain.
link |
Now, not completely numb,
link |
but they numb or reduce our perception of pain
link |
because of the ways in which they are released
link |
from certain brain centers.
link |
We'll talk about those brain centers in a moment.
link |
So what's really interesting is that this study showed
link |
that the presence of these hormones is in everybody.
link |
We all have melanocortin-4,
link |
we all have beta-endorphins,
link |
we all have POMC, et cetera,
link |
but redheads make more of these endogenous endorphins.
link |
And that's interesting.
link |
It allows them to buffer against the pain response.
link |
I have a personal anecdote to share with you
link |
about this redhead and heightened levels
link |
of pain tolerance phenomenon.
link |
Obviously, I'm not a redhead.
link |
I don't dye my hair,
link |
but my partner for many years was a redhead
link |
and still is a redhead.
link |
She had bright red hair and had that since childhood.
link |
Well, we had the fortunate experience
link |
of becoming friends with Wim Hof and family.
link |
They actually came out to visit us
link |
and did a series of seminars in the Bay Area.
link |
This was in 2016, as I recall.
link |
And my partner, she had never done an ice bath.
link |
She had never done any kind of real cold water
link |
exposure experience before,
link |
but it is one particular gathering,
link |
as is often the case when Wim is around,
link |
there was an ice bath
link |
and a number of people were getting into this thing.
link |
This was actually before a dinner event.
link |
And I think for most people
link |
who have never done an ice bath,
link |
getting in for 30 seconds or a minute is tolerable,
link |
but it takes some effort,
link |
it takes some willpower
link |
and takes some overcoming that pain barrier
link |
because it is a little bit painful, not a lot.
link |
Some people can stay in longer, three minutes,
link |
five minutes without much discomfort.
link |
What was incredible is that without any desire
link |
to compete with anybody else,
link |
my partner, redhead, got into the ice bath
link |
and just like sat there for 10 minutes.
link |
In fact, at one point, she just kind of turned to me
link |
and said, you know, I don't really feel pain.
link |
I'm not really in pain.
link |
And Wim loved this.
link |
Wim thought it was great.
link |
He thought it was like the most terrific thing in the world.
link |
And he got back in the ice bath
link |
and they became fast friends.
link |
And I think they're probably still fast friends.
link |
So in any event, that's an N of one,
link |
what we call an anecdata example.
link |
Anecdata is not really a term that we should use too much
link |
because it's N of one anecdotes are just that,
link |
they're just anecdotes.
link |
But it's been described many times in various clinics
link |
that were by anesthesiologists,
link |
by observation of coaches, et cetera,
link |
that redheads, men and women who are redheads,
link |
seem to have this higher pain threshold.
link |
And it does seem to be because their body naturally produces
link |
ways to counter the pain response.
link |
They produce their own endogenous opioids.
link |
Now, this of course should not be taken to mean
link |
that redheads can tolerate more pain
link |
and therefore should be subjected to more pain.
link |
All it means is that their threshold for pain on average,
link |
not all of them, but on average,
link |
is shifted higher than that of other individuals.
link |
And it remains to be determined whether or not
link |
other light-skinned, light-haired individuals
link |
also have a heightened level of pain threshold.
link |
And I should mention, because I mentioned the ice bath,
link |
that of course pain threshold is something
link |
that can be built up and provided you do that safely
link |
in ways that aren't damaging your tissues,
link |
because of course, pain is a signal that is designed
link |
to help you to keep from harming yourself,
link |
but provided that you can do that in a way that's safe
link |
and doesn't damage your tissues,
link |
increasing your pain threshold through the use of things
link |
like ice baths is something that really can be done.
link |
It has a lot to do with these contextual
link |
or top-down modulations of the experience.
link |
You can tell yourself that this is good for me,
link |
or I'm doing this by choice or whatever it is,
link |
you could distract yourself.
link |
There are a huge number of different ways
link |
that one could do that.
link |
One of the more interesting ways for which there are
link |
actually really good scientific data
link |
come from my colleague, Sean Mackey's lab.
link |
And that actually looked at how love,
link |
and in particular the experience of obsessive love,
link |
could actually counter the pain response,
link |
not just in redheads, but in everybody.
link |
So that study, I'll just briefly describe,
link |
it involved having people come into the laboratory
link |
and experience any one or a number
link |
of different painful stimuli,
link |
but they had selectively recruited subjects
link |
that were in new relationships
link |
for which there was a high degree of infatuation,
link |
so much so that the people couldn't stop thinking about
link |
or communicating with that new partner
link |
up to 80% of their waking time, which is a lot.
link |
That constant obsessing about that partner
link |
was correlated with, it wasn't causal necessarily,
link |
but was correlated with the ability
link |
to sustain higher levels of pain
link |
than people who were in more typical
link |
non-obsessive forms of love,
link |
longstanding relationships
link |
where there wasn't long obsessive love rather.
link |
And of course, in this study,
link |
there were a lot of good control groups.
link |
They included a distractor,
link |
they included people obsessing about other things,
link |
their pet, et cetera.
link |
They included other forms of love and attachment,
link |
but it does seem that certain patterns of thinking
link |
can allow us to buffer ourselves against the pain response.
link |
And that should not be surprising.
link |
Certain forms of thinking are associated
link |
with the release of particular neuromodulators,
link |
in particular dopamine.
link |
And dopamine, it may seem is kind of the thing
link |
that underlies everything, but it's not.
link |
Dopamine is a molecule that's associated
link |
with novelty, expectation, motivation, and reward.
link |
We talked about this at the beginning of the episode,
link |
that it's really the molecule of expectation
link |
and motivation and hope and excitement
link |
more than it's associated with the receival of the reward.
link |
Well, dopamine is coursing throughout the brain
link |
at heightened levels and coursing throughout the body
link |
at heightened levels when we fall in love.
link |
This probably has some adaptive mechanism
link |
that ensured pair bonding between people,
link |
or who knows, maybe it ensured
link |
not bonding to multiple people.
link |
Nobody really knows how dopamine functions
link |
in terms of pair bonding,
link |
but it is known that when people fall in love,
link |
new relationships create very high levels of dopamine.
link |
And that's probably the mechanistic basis
link |
by which these people were able to buffer the pain response
link |
by thinking about their partner,
link |
this new relationship that they're in
link |
almost obsessively or obsessively.
link |
Now that raises a deeper question.
link |
We should always be asking, yeah, but how, how?
link |
Well, the dopamine system can have powerful effects
link |
on the inflammation system.
link |
And it doesn't do this through mysterious ways.
link |
It does this by interacting through the brainstem
link |
and some of the neurons that innervate the spleen
link |
and other areas of the body that deploy cells
link |
to go combat infection, inflammation, and pain.
link |
And the ways in which dopamine can modulate pain,
link |
and in this case, this particular study,
link |
transform our experience of pain,
link |
maybe even into something that's pleasureful,
link |
is not mysterious.
link |
It's really through the activation of brainstem neurons
link |
that communicate with areas of our body
link |
that deploy things like immune cells.
link |
So for instance, we have neurons in our brainstem
link |
that can be modulated by the release of dopamine.
link |
And those neurons in the brainstem
link |
control the release of immune cells
link |
from tissues like the spleen or organs like the spleen.
link |
And those immune cells can then go combat infection.
link |
We've heard before that when we're happy,
link |
we're better able to combat infection,
link |
deal with pain, deal with all sorts of things.
link |
It essentially makes us more resilient.
link |
And that's not because dopamine is some magic molecule.
link |
It's because dopamine affects particular circuits
link |
and tells in a very neurobiological way,
link |
in a biochemical way, tells those cells and circuits
link |
that conditions are good.
link |
Despite the fact that there's pain in the body,
link |
conditions are good.
link |
You're in love or conditions are good.
link |
You want to be in this experience or conditions are good.
link |
This is for a greater cause that you're fighting
link |
or suffering for some larger purpose.
link |
So all of that has existed largely in the realm of
link |
psychology and even motivational literature
link |
and this kind of thing.
link |
But there's a real mechanistic basis for it.
link |
Dopamine is a molecule that can bind to receptor sites
link |
on these brain areas.
link |
Those brain areas can then modulate the organs
link |
and tissues of the body that can allow us
link |
to lean into challenge.
link |
And those challenges can be infection.
link |
It can be physical pain.
link |
It can be long bouts of effort that are required of us.
link |
And I think many people have described the feeling
link |
of being newly in love as a heightened level of energy,
link |
a capacity to do anything.
link |
I mean, the whole concept of a muse is one in which
link |
some individual or some thing either imagined or real
link |
enters our life and we can use that as fuel.
link |
And that fuel is chemical fuel
link |
and that chemical fuel is dopamine.
link |
And it really does allow for more resilience
link |
and can even transform the experience of pain
link |
or what would otherwise be pain
link |
into an experience of pleasure.
link |
So along those lines, let's talk about pleasure.
link |
With all the cells and tissues and machinery related
link |
to pain, you might think that our entire touch system
link |
is designed to allow us to detect pain
link |
and to avoid tissue damage.
link |
And while a good percentage of it is devoted to that,
link |
a good percentage of it is also devoted
link |
to this thing that we call pleasure.
link |
And that should come as no surprise.
link |
Pleasure isn't just there for our pleasure.
link |
It serves an adaptive role.
link |
And that adaptive role relates to the fact
link |
that every species has a primary goal,
link |
which is to make more of itself.
link |
Otherwise it would go extinct.
link |
That process of making more of itself, sexual reproduction,
link |
is closely associated with the sensation
link |
and the perception of pleasure.
link |
And it's no surprise that not only is the highest density
link |
of sensory receptors in and on and around the genitalia,
link |
but the process of reproduction evokes sensations
link |
and molecules and perceptions associated with pleasure.
link |
And the currency of pleasure
link |
exists in multiple chemical systems,
link |
but the primary ones are the dopamine system,
link |
which is the anticipation of pleasure
link |
and the work required to achieve the ability
link |
to experience that pleasure
link |
and the serotonin system,
link |
which is more closely related
link |
to the immediate experience of that pleasure.
link |
And from dopamine and serotonin,
link |
stem out other hormones and molecules,
link |
things like oxytocin,
link |
which are associated with pair bonding.
link |
Oxytocin is more closely associated
link |
with the serotonin system,
link |
biochemically and at the circuit level,
link |
meaning the areas of the brain and body
link |
that manufacture a lot of serotonin,
link |
usually, not always, but usually contain neurons
link |
that also manufacture
link |
and make use of the molecule oxytocin.
link |
Those chemicals together create sensations of warmth,
link |
of wellbeing, of safety.
link |
The dopamine molecule is more closely associated
link |
with hormones like testosterone
link |
and other molecules involved with pursuit
link |
and further effort in order to get more of whatever
link |
could potentially cause more release of dopamine.
link |
So this is a very broad strokes, no pun intended,
link |
description of the pleasure system.
link |
There are of course other molecules as well.
link |
One in particular that's very interesting
link |
is something called PEA.
link |
PEA stands for phenylethylamine,
link |
sometimes also referred to as phenylethylamine,
link |
depending on who you are and where you live.
link |
How you pronounce it doesn't really matter.
link |
PEA is a molecule which is incredibly potent
link |
at augmenting or increasing the activity
link |
of certain cells and neural circuits
link |
that relate to the pleasure system.
link |
PEA has purportedly been thought to be released
link |
in response to ingestion of things
link |
like certain forms of dark chocolate.
link |
Some people take it in supplement form.
link |
It's a bit of a stimulant,
link |
but it also seems to heighten the perception of pleasure
link |
in response to a particular amount
link |
of dopamine and or serotonin.
link |
So for instance, in a kind of a arbitrary experiment
link |
and units type example,
link |
if a given experience evokes a particular amount
link |
of serotonin and dopamine and gives rise
link |
to a subjective experience of pleasure
link |
of say level three out of 10,
link |
the ingestion of PEA prior to that experience
link |
can increase the rating of that experience
link |
as more pleasureful, maybe a four or a five or even a six.
link |
And PEA is known to be present in,
link |
or I should say its release is stimulated
link |
by a number of different compounds, such as dark chocolate,
link |
certain things like aspartame and certain people
link |
can actually increase the amount of PEA released.
link |
Some of these glutamate related molecules like aspartame
link |
or things that are in the glutamate pathway
link |
can increase PEA release.
link |
And then some people will actually take PEA
link |
in supplement form for its mild stimulant properties
link |
as well as for increasing the perception of
link |
or the ability to experience pleasure.
link |
It's not a sledgehammer.
link |
It's not a like dopamine itself.
link |
People that take things like macuna purines,
link |
L-DOPA or drugs of abuse,
link |
which I certainly don't recommend,
link |
things like cocaine or amphetamine
link |
experience tremendous increases in dopamine,
link |
not so much increases in serotonin.
link |
Some people will take serotonin in precursor form
link |
like 5-HTP or serotonin itself,
link |
or they'll take the amino acid precursor like tryptophan.
link |
I'm not saying these things as recommendations
link |
for increasingly one sense of pleasure.
link |
I'm describing them because of what they do
link |
generally falls into two categories.
link |
The first category is to raise the foundation,
link |
what we call the tonic level of dopamine and serotonin.
link |
So if levels of serotonin and dopamine are too low,
link |
it becomes almost impossible to experience pleasure.
link |
There's a so-called ahedonia.
link |
This is also described as depression,
link |
although it needn't be long-term depression.
link |
So certain drugs like antidepressants,
link |
like Wellbutrin, Bupriarone as it's commonly called,
link |
or the so-called SSRIs,
link |
the serotonin selective reuptake inhibitors, excuse me,
link |
like Prozac, Zoloft and similar
link |
will increase dopamine and serotonin respectively.
link |
They're not increasing the peaks in those molecules.
link |
The, what we call the acute release of those molecules,
link |
what they're doing is they're raising
link |
the overall levels of those molecules.
link |
They're raising the sort of foundation or the tide,
link |
if you will, think about it as your mood
link |
or your pleasure rather is like a boat.
link |
And if it's on the shore and it can't get out to sea
link |
unless that tide is high enough,
link |
that's kind of the way to think about these tonic levels
link |
of dopamine and serotonin.
link |
Now, most of us fortunately do not have problems
link |
with our baseline or our tonic levels
link |
of dopamine and serotonin release.
link |
Things like PEA in that case
link |
will cause a slight increase in that tide
link |
and make the ability of certain experiences
link |
to increase dopamine further more available.
link |
What we call this in neuroscience is so-called gain control.
link |
It can kind of turn up the volume,
link |
bring us closer to the threshold
link |
to activate certain circuits.
link |
And this is really what we mean
link |
when we say a neuromodulator, okay?
link |
This is why when you are very happy about something,
link |
let's say you're out with your friends,
link |
you're really excited, you know,
link |
maybe depending on where you live
link |
and what's going on in your area of the world right now,
link |
like, you know, like I have a niece
link |
and she's been locked up in quarantine
link |
for a long time recently because it was deemed safe.
link |
She got to go to summer camp.
link |
I have never seen that kid so happy to spend,
link |
excuse me, spend time with her friends.
link |
She was so excited and it was really amazing
link |
to see how excited she was.
link |
Her baseline levels of dopamine were clearly up,
link |
so much so that when she saw her friends,
link |
she literally started squealing, okay?
link |
They were squealing, she was squealing.
link |
Everyone was squealing.
link |
I wasn't squealing.
link |
I would admit it if I was squealing.
link |
I wasn't squealing, but it was such a delight to see
link |
and I'm sure that made my dopamine levels go up,
link |
which was she was just so excited,
link |
such that anything and everything
link |
felt like an exciting stimulus.
link |
This is pleasure, right?
link |
And I don't want to write off the experience
link |
from a neurobiological reductionist standpoint
link |
quite the opposite.
link |
It's really beautiful to see, again,
link |
this principle that different experiences
link |
and the experience of pleasure from different things,
link |
seeing your friends for the first time,
link |
summer camp for a kid, whatever it might happen to be,
link |
use the same currency, dopamine,
link |
use the same currency, serotonin.
link |
And this is a principle that I hope
link |
in listening to this podcast
link |
and even some of its repetitive features
link |
from one episode to the next,
link |
I'm hoping that those will start to embed in your mind
link |
that the brain and body use these common currencies
link |
for different experiences.
link |
So yes, if your dopamine and serotonin,
link |
or I should say if your dopamine
link |
and or serotonin levels are too low,
link |
it will be very hard to achieve pleasure,
link |
to experience physical pleasure
link |
or emotional pleasure of any kind.
link |
That's why treatments of the sort
link |
that I described a minute ago might be right for you.
link |
Obviously we can't determine if they're right for you.
link |
It's also why they have side effects.
link |
If you artificially increase these molecules
link |
that are associated with pleasure,
link |
oftentimes you get a lack of motivation
link |
to go seek things like food.
link |
People don't get much interest in food
link |
because why should they
link |
if their serotonin levels are already up?
link |
Again, there's a ton of individual variation.
link |
I don't want to say that these antidepressants
link |
Sometimes they've saved lives.
link |
They've saved millions of lives.
link |
Sometimes people have side effects
link |
that make them not the right choice.
link |
So it has to be determined for the individual.
link |
Things like PEA are a more subtle effect.
link |
I should mention PEA supplementation
link |
is something that a number of people use,
link |
but it's very short-lived.
link |
Because of the half-life of this molecule is very brief,
link |
the effect only lasts about 20 minutes or so.
link |
Things like L-DOPA and the cunipurines
link |
lead to longer baseline increases in dopamine.
link |
But remember, anytime you raise a baseline,
link |
you reduce the so-called signal to noise.
link |
What it means is if you're riding around
link |
at really high dopamine,
link |
at first, everything will start to seem exciting,
link |
like my niece and seeing her friends for the first time.
link |
Everything's exciting.
link |
But then what will happen is
link |
when your dopamine levels return to more normal levels,
link |
it will take a much greater dopamine increase,
link |
a much bigger event, more novel, more exciting,
link |
in order to achieve the sense
link |
that what you're experiencing is pleasureful.
link |
And this is because of the relationship
link |
between pleasure and pain.
link |
Now, in a future episode,
link |
we are going to go deep into this relationship
link |
between pleasure and pain.
link |
But just briefly, as a precursor to that,
link |
and because it's relevant
link |
to the conversation that we've been having,
link |
you might want to be wary of any experience,
link |
any experience, no matter how it arrives,
link |
chemical, physical, emotional, or some combination.
link |
You might want to be wary
link |
of letting your dopamine go too high,
link |
and certainly you want to be wary of it going too low
link |
because of the way that these circuits adjust.
link |
Basically, every time that the pleasure system
link |
is kicked in in high gear,
link |
an absolutely spectacular event,
link |
you cannot be more ecstatic.
link |
There is a mirror symmetric activation of the pain system.
link |
And this might seem like an evil curse of biology,
link |
This is actually a way to protect this whole system
link |
of reward and motivation
link |
that I talked about at the beginning of the episode.
link |
It might sound great to just ingest substances
link |
or engage in behaviors where it's just dopamine,
link |
dopamine, dopamine, and just constantly be motivated,
link |
but the system will eventually crash.
link |
And so what happens
link |
is when you have a big increase in dopamine,
link |
you also will get a big increase in the circuits
link |
that underlie our sense of disappointment
link |
and readjusting the balance.
link |
And with repeated exposure to high levels of dopamine,
link |
not naturally occurring, wonderful events,
link |
but really high chemically induced peaks in dopamine,
link |
high magnitude chemically induced peaks in dopamine,
link |
what happens is those peaks in dopamine
link |
start to go down and down and down
link |
in response to the same
link |
what ought to be incredible experience.
link |
We start to what's called habituate or attenuate,
link |
and yet the pain increases in size.
link |
And this has a preservative function
link |
in keeping us safe, believe it or not.
link |
But what I just described is actually the basis
link |
of most, if not all forms of addiction,
link |
something that we will deal with
link |
in a future episode in depth.
link |
So what should you think about all this?
link |
How should you think about pleasure
link |
and how should you think about pain?
link |
What is too much pleasure?
link |
Well, that's going to differ from person to person,
link |
but to the extent that one can access pleasure repeatedly
link |
over time, ideally without chemical augmentation,
link |
certainly not excessive chemical augmentation,
link |
that means that this pleasure system is tuned up well
link |
and can continue to experience pleasure.
link |
However, if you find yourself engaging
link |
in the same behavior over and over again,
link |
but achieving less and less pleasure from it,
link |
chances are you want to adjust down
link |
how often you engage in that behavior
link |
and or adjust down your expectation of reward
link |
every time you engage in that behavior.
link |
What do I mean by that?
link |
Well, at the beginning of the episode,
link |
I talked about how dopamine will allow us
link |
to get into bouts of hard work.
link |
We will work very hard to pursue a reward
link |
and that's really what dopamine does.
link |
And then when the reward comes,
link |
that doesn't increase our dopamine.
link |
In fact, our dopamine levels go down.
link |
One of the key things that we can all do
link |
to adjust our ability to experience pleasure
link |
is to engage in that intermittent reward schedule.
link |
You can either adjust down the peak in dopamine,
link |
meaning not let yourself ever get too happy,
link |
but that's no fun, right?
link |
Life is about occasionally achieving or experiencing ecstasy
link |
but every once in a while, remove the reward.
link |
And of course I don't mean ecstasy the drug,
link |
that's a separate matter.
link |
The MDMA trials are a separate matter, very interesting.
link |
I want to be clear, I meant psychological
link |
and physical ecstasy of the natural sort.
link |
I've immense interest in what's going on in the MDMA trials
link |
but just for clarity purposes,
link |
that's a separate topic that we will cover
link |
in an episode, excuse me, very soon.
link |
So how do you adjust this dopamine system?
link |
Well, every once in a while at random,
link |
not in a predictable way, you remove the reward
link |
and that will keep you and your dopamine system tuned up
link |
in the proper ways.
link |
The gain of the dopamine system, as we say,
link |
will be adjusted so that you can continue
link |
to experience dopamine and serotonin
link |
when you actually get the reward.
link |
This can be translated into a huge number
link |
of different domains, but I want to give some examples
link |
because I'm sure that many of you are asking,
link |
wait, what does this actually mean?
link |
Okay, let's say you're a student
link |
or this could be a student in academia
link |
or this could be a student of a physical practice.
link |
Every once in a while, when you do something really well,
link |
maybe that's even just showing up to the practice.
link |
Rather than pat yourself on the back,
link |
just tell yourself, yeah,
link |
that's the minimum that's expected of me.
link |
When everyone's excited about something that you're doing,
link |
maybe you're excited about it,
link |
try and adjust down your excitement a little bit.
link |
I know this might seem counterintuitive,
link |
but you're preserving the ability
link |
to experience excitement in a variety of contexts.
link |
Let's say you get a big monetary award.
link |
Well, that's great, I'm happy for you and that's wonderful.
link |
However, you should be a little bit wary
link |
if you care about your dopamine system
link |
and you care about your ability
link |
to get subsequent monetary rewards,
link |
excuse me, awards, rewards, doesn't matter which,
link |
If you want to be able to maintain the ability
link |
to exert effort, well, then you probably wouldn't want
link |
to run out and immediately buy something
link |
with that monetary reward.
link |
In other words, you wouldn't want to layer on
link |
more dopamine release, okay?
link |
You might, but you might not, you might skip it.
link |
What you'll find then is that your motivation
link |
is essentially infinite.
link |
This is what I described at the beginning of the episode.
link |
And again, it's because dopamine is this currency.
link |
It's like, these days you hear a lot about Bitcoin
link |
and Ethereum and Dogecoin and US dollars and euros
link |
and all this other stuff.
link |
But the currency that you use in your body
link |
doesn't matter what external currency those are.
link |
In fact, as you watch the value of different currencies
link |
go up, whether or not it's cryptocurrency
link |
or standard currency, the value is actually reflective
link |
of the dopamine that exists inside of people, right?
link |
So all the excitement about a particular currency,
link |
crypto or otherwise, is really just dopamine.
link |
That's the currency that we all use.
link |
And there's no negotiating that.
link |
That's just the way that we're built.
link |
Now, to give yet other examples,
link |
let's say you're teaching other people how to do something
link |
and they do something exceptionally well.
link |
If you reward them every single time,
link |
and in particular, if you reward them with something
link |
that's even greater than the experience of what they did.
link |
So let's say kids win a soccer game and they're ecstatic,
link |
they're jumping all over the place, they're super excited,
link |
and you reward them with an even bigger experience,
link |
a celebration, you are actually inhibiting their ability
link |
to perform the same set of activities
link |
that led them to the win.
link |
If, and I really want to underscore,
link |
if you reward them every time.
link |
Of course, we should reward kids and each other
link |
and ourselves for our accomplishments,
link |
but you don't want to do it every time.
link |
And sure, there will be some disappointment
link |
from suddenly removing the reward that you expected,
link |
but that's exactly the point.
link |
That's what keeps these circuits tuned up properly.
link |
Now there's the other form of pleasure,
link |
which is the more immediate visceral
link |
or sensory experience of pleasure.
link |
This is distinct from goals and goal-directed behavior.
link |
I'm talking about the immediate experience.
link |
This is more of the serotonergic system.
link |
There are other systems involved too,
link |
but this is also the system that draws out
link |
those endogenous opioids from a particular structure.
link |
We have a structure in the back of our brain called PAG,
link |
P-A-G, it's the periaqueductal gray area.
link |
Very interesting brain area that is associated with pain,
link |
but also with pleasure because under certain conditions,
link |
it deploys endogenous opioids
link |
and gives us a kind of blissed out feeling, okay?
link |
This is not like the opioids of the opioid epidemic sort
link |
that people take and unfortunately have led
link |
to tremendous amounts of suffering and abuse.
link |
These are endogenously released opioids.
link |
These are the kind of opioids that come out
link |
from long distance bouts of physical exercise and running.
link |
These are the opioids that are deployed
link |
in response to giving birth
link |
and overcoming the tremendous pain of childbirth.
link |
So PAG is very contextual
link |
and there are a few types of stimuli,
link |
or I should say events in life.
link |
I'm really showing my nerdy side.
link |
There are a few types of stimuli,
link |
I'm talking about experiences
link |
that evoke endogenous opioid release from PAG.
link |
One is sexual activity.
link |
Sexual activity can increase pain threshold.
link |
And here I am not suggesting or getting involved
link |
in anyone's particular proclivities or personal experiences.
link |
You're welcome to editorialize this however you like.
link |
However, what I'm talking about are animal data
link |
and yes, human data as well
link |
that show that pain thresholds are increased
link |
anytime PAG is activated
link |
because of the release of these endogenous opioids.
link |
There's also the immediate experience
link |
of whether or not a particular form of touch
link |
is pleasureful or not.
link |
And there there's some very interesting biology
link |
that relates to really how those little wires
link |
from those DRGs innervate our skin.
link |
Work studies, I should say,
link |
done by David Ginty's lab at Harvard Medical School.
link |
The Ginty lab has spent years
link |
working on the somatosensory system, the touch system,
link |
has identified a particular category of neurons
link |
that innervate the skin.
link |
And then those neurons, of course,
link |
send that information up to the brain too.
link |
And they actually respond to direction of touch.
link |
Now, some of you might be more sensitive to this
link |
than others, but it turns out that certain hairs
link |
like to be deflected one way versus another.
link |
Whether or not you like cats or not,
link |
you can do this experiment.
link |
You can pet a cat in the direction that their fur lies.
link |
So it lies down in a particular direction.
link |
You'll notice that there's actually a gene
link |
that dictates that the hairs lie down
link |
in a particular direction.
link |
And if you pet them in a way that's
link |
cooperating with that direction,
link |
so not pushing the hairs up,
link |
but rather stroking the hairs on the back of the cat,
link |
what you'll notice is they often like that.
link |
Not all cats, some cats are pretty grouchy,
link |
but if you stroke their hair, they will often purr,
link |
they'll often push into you.
link |
If you were to stroke their hair in the opposite direction,
link |
pushing the hairs up against the direction
link |
that they want to lie down, cats do not like that.
link |
And it turns out people don't like that either.
link |
Some people do like to have their hair pushed
link |
in a direction against the direction
link |
in which it wants to lay down,
link |
but there is more typically a response
link |
of feeling like it's pleasurable for,
link |
for instance, when someone brushes or combs their hair
link |
in the direction that it wants to lay down.
link |
And that's because the way in which these neurons
link |
that innervate these hairs sends information
link |
up to the brain, bifurcates actually,
link |
it splits into brain centers that evoke a sense of pleasure
link |
or a sense of not pleasure.
link |
It's not necessarily pain.
link |
So you might find that certain people are very particular.
link |
They like to be touched in a certain way, but not others.
link |
You might be one of those people.
link |
And areas of our skin that have high density of receptors
link |
are very, very sensitive in a real way,
link |
in a real sense of the word, to patterns of touch
link |
and whether or not a touch is too firm or too light.
link |
And that will be modulated by overall levels of arousal.
link |
And when I talk about arousal,
link |
what I'm talking about is how alert or how sleepy we are.
link |
It is impossible to experience pain
link |
when we are deep in sleep.
link |
I don't mean sleeping like of the typical night sword.
link |
I mean of the anesthesia sword.
link |
That's the purpose of anesthesia,
link |
to bring the brain and body into a deep plane of rest,
link |
very deep, in fact.
link |
And it's very hard, if not impossible,
link |
to achieve or experience pleasure
link |
when we are in a very low state of arousal as well.
link |
When we are in heightened states of arousal,
link |
we can achieve pain, we can experience pain,
link |
and we can experience pleasure, okay?
link |
And under those heightened states of arousal,
link |
we are more sensitive, literally,
link |
the passage of electrical signals
link |
from those locations on the body
link |
that have heightened degrees or higher degrees,
link |
I should say, of receptors, use your imagination.
link |
They include the lips, the face, the feet, and the genitals,
link |
and nearby areas, literally nearby areas.
link |
Under conditions of high arousal, two things happen.
link |
The ability to achieve or experience pleasure
link |
at those locations goes up,
link |
and our tolerance and our threshold for pain also goes up.
link |
So the principle here is that as our levels of arousal,
link |
that foundation of arousal goes up or down,
link |
so too goes up and down our ability
link |
to achieve pleasure and pain.
link |
And so these two extremes of being deep within anesthesia,
link |
or another extreme is asleep,
link |
or in heightened levels of arousal,
link |
our ability to achieve pleasure and pain
link |
are going to scale according to those.
link |
And this is why, and I'm certainly not suggesting this,
link |
but this is why some people will take stimulants
link |
or drugs of abuse that increase arousal
link |
in order to achieve pleasure of other kinds.
link |
The problem is is that those drugs,
link |
in particular things like cocaine and methamphetamine
link |
and amphetamine, become their own form of reinforcement,
link |
so much so that the person doesn't seek out
link |
any other form of excitement or arousal, okay?
link |
So today we weren't talking about addiction.
link |
We weren't necessarily talking about motivation,
link |
but we touched on those topics
link |
as sort of a precursor of what's to come.
link |
We talked about the pathways in the skin and in the brain
link |
and elsewhere in the body
link |
that control our sense of pleasure and pain.
link |
We described a number of different tools
link |
ranging from hypnosis to different supplements
link |
to electroacupuncture and various other tools
link |
that one could use to modulate
link |
your sense of pleasure or pain.
link |
And of course, in thinking about pleasure,
link |
we have to think about the dopamine system
link |
and the serotonin system
link |
and some of the related chemical systems.
link |
I realized that today's podcast
link |
had a lot of scientific details.
link |
We've timestamped everything for you
link |
so that you don't have to digest it all at once, of course.
link |
I don't expect that everyone would be able to understand
link |
all these details all at once.
link |
What's more important really
link |
is to understand the general principles
link |
of how something like pleasure and pain work,
link |
how they interact and the various cells and systems
link |
within the brain and body that allow them to occur
link |
and that modulate or change their ability to occur.
link |
And of course, your subjective experience
link |
of pleasure or pain.
link |
So I do hope that this was on whole
link |
more pleasureful than painful for you.
link |
If you're enjoying this podcast
link |
and you're learning from it and you'd like to support us,
link |
you can do that in a number of different ways,
link |
some of which are totally cost-free.
link |
The first one is please subscribe to the YouTube channel.
link |
That really helps us.
link |
In addition, you can leave us comments and suggestions
link |
for future podcast episodes on the YouTube channel.
link |
You can also subscribe on Apple and or Spotify
link |
or all three that would really help us.
link |
And on Apple, you can leave us up to a five-star review
link |
and leave us feedback.
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There are other ways to support the podcast as well.
link |
We have a Patreon, that's patreon.com slash Andrew Huberman.
link |
And there you can support the podcast
link |
at any level that you like.
link |
In addition, please check out our sponsors
link |
that we mentioned at the beginning of the podcast.
link |
We only work with sponsors and brands
link |
that we absolutely love their products
link |
and that we wholeheartedly endorse
link |
and that we use ourselves.
link |
In addition, we've partnered with Thorne.
link |
Thorne is a supplement company
link |
and we've partnered with them
link |
because they have the highest levels of stringency
link |
in terms of the quality of the ingredients they use
link |
and the quantity of the ingredients they use.
link |
By quantity, I mean that unlike a lot
link |
of supplement companies out there,
link |
the amounts that are listed on the bottle
link |
are absolutely what you find
link |
in those capsules and tablets in the bottle.
link |
If you go to Thorne, that's T-H-O-R-N-E
link |
slash the letter U slash Huberman,
link |
you can see the supplements that I take
link |
and you can get 20% off any of those supplements
link |
as well as any of the other supplements that Thorne makes.
link |
Just go into the Thorne site through that portal,
link |
Thorne slash U slash Huberman.
link |
And even if you navigate off from that location in the site,
link |
you'll get 20% off any of the items that you might select
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from other locations within the Thorne site.
link |
If you're not already following us on Instagram,
link |
it's Hubermanlab at Instagram.
link |
And there I do various tutorials about neuroscience,
link |
offer neuroscience-related tools, all backed by science.
link |
And last but not least,
link |
I thank you for your time and attention
link |
and thank you for your interest in science.
link |
I'll see you in the next one.