Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I’m Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine. This podcast is separate from my teaching and research roles at Stanford, but is part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I’d like to thank the sponsors of today’s podcast. Our first sponsor is ExpressVPN, a virtual private network that keeps your data secure by routing your data and online activities through their servers and keeping your data safe and secure, but also not selling your data to third parties.

I started using ExpressVPN because unfortunately I had my bank accounts hacked. I was traveling a lot and I typically go on hotel or airline or other public Wi-Fi from time to time and I don’t know how it happened, but somehow my information got out there. As I learned more from my friends and people that work in the tech community, it turns out that many networks are not secure. With ExpressVPN, it keeps all your information secure, including passwords.

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We really appreciate your interest in helping us keep this coming your way. Thank you. Let’s continue our discussion about neuroplasticity – this incredible feature of our nervous system that allows it to change itself in response to experience, and even in ways that we consciously and deliberately decide to change it. No other organ in our body has that capability, yet our nervous system, which governs everything about who we are, how we feel and what we do, does have that capability. The issue is most people don’t know how to access neuroplasticity. Children readily access neuroplasticity and they don’t even realize that they’re doing it. Adults want neuroplasticity and so that’s what this entire month of the Huberman Lab Podcast has been about. Thank you for your interest.

We’ve explored neuroplasticity from a variety of different perspectives. Representational plasticity, the importance of focus and reward, and the amazing and somewhat surprising aspect of the vestibular system were discussed. Altering our relationship to gravity and making errors as we try and learn can open up windows to plasticity. However, we have not talked about how to direct the plasticity toward particular outcomes, or how to undo things that we don’t want. Today, we are going to explore this aspect of neuroplasticity in the context of pain regeneration and injury to the nervous system. We will discuss some of the science, as well as the mechanisms and principles. Principles are far more important than any one experiment, description of mechanism, or protocol, as they allow us to think about our nervous system and work with it in ways that best serve us.

We are going to talk about the principles of neuroplasticity for removing pain and wound healing and injury. Acupuncture is one of the topics we will cover, as well as modern medicine’s attempts to restore youth to aging, injured, or demented brains. We will also discuss the various tools available and the information provided in this podcast should not be taken as medical advice. I consulted with colleagues at Stanford, Harvard Medical School, and other tissue rehabilitation, injury, and pain management experts in preparation for this podcast. Always consult with your doctor or healthcare provider before adding or removing any tools from your daily protocols.

Don’t change anything without consulting an expert first. You are responsible for your health, not me, and I say this not just to protect me but also to protect you. Please keep that in mind as we move forward and I’m very excited to share with you this information because I do feel that it can be of great benefit to a number of people.

Let’s start our discussion about pain and sensation and regeneration and wound healing with a discussion about a very important system in the nervous system, which is the somatosensory system. The somatosensory system is, as the name implies, involved in understanding touch, physical feeling on our body, and the simplest way to think about the somatosensory system is that we have little sensors and those sensors come in the form of neurons, nerve cells, that reside in our skin and in the deeper layers below the skin.

We have some that correspond to, and we should say respond to, mechanical touch, so pressure on the top of my hand or a pinpoint, or other sensors, for instance, respond to heat, to cold. Some respond to vibration. We have a huge number of different receptors in our skin and they take that information and send it down these wires that we call axons in the form of electrical signals to our spinal cord and then up to the brain.

Within the spinal cord and brain, we have centers that interpret that information, that actually make sense of those electrical signals, and this is amazing because none of those sensors has a different unique form of information that it uses. It just sends electrical potentials into the nervous system. The nervous system, you somehow decode what a given stimulus on your skin is.

Pain is a complex experience that involves both physical and mental components. It is detected by nociceptors, which are sensors in the skin that detect particular types of stimuli. The Latin word nocere, meaning to harm, is where the word nociception comes from. Pain is a controversial word in the neuroscience field because it is very subjective and cannot be simply explained as an attempt to avoid physical harm to the body. Action potentials are electrical signals that arrive in the nervous system to alert the brain and spinal cord of sensations, such as the wind blowing gently across the skin or a sharp pinprick. The brain then computes these signals and makes sense of them.

They took him to the hospital, did a physical examination and a scan of the area, and there was no tissue damage.

Exposure to high levels of radiation, such as working with radioactive material or being near a former radioactive plant, can cause tissue damage without the physical or mental perception of pain. As well, there can be the belief of pain or the feeling of pain without there being tissue damage. A famous case published in the British Journal of Medicine illustrates this. A construction worker experienced excruciating pain when a 14-inch nail went through his boot, yet there was no tissue damage when examined in the hospital.

They brought him into the clinic, into the hospital, where they were able to cut away the boot and realized that the nail had gone between two toes and had not impaled the skin at all. His visual image of the nail going through his boot gave him the feeling that he was experiencing the pain of a nail going through his foot, which speaks to the power of the mind in this pain scenario and the power of specificity. This example shows that pain and tissue damage are dissociable from one another.

Pain offers us principles to understand the difference between injury and pain, interpret our pain, and eliminate pain from both ends of the spectrum. A colleague of mine is working on and has published data on the role of love in modulating the pain response. It turns out that the specific type of connection one has to a romantic partner dictates whether or not their love for them will alleviate physical pain and the effects are really robust.

Plasticity of perception has a direct bearing on emotional pain and trauma. In an entire month about these topics, we will explore what happens with pain. I will describe some extreme cases, such as a genetic mutation in a particular sodium channel found in neurons. This sodium channel, called 1.7, is essential for the function and development of certain neurons. Kids born without this sodium channel experience no pain whatsoever, which is a terrible situation as they can burn themselves or rest on their limbs too long without making the necessary microadjustments.

You might see me swiveling around in my chair, making microadjustments. These are normal and healthy, preventing us from going into pain. People who don’t make these adjustments don’t get the feedback that they’re in a particular position and, as a result, their joints can become destroyed. It’s a terrible circumstance, and some people with a mutation in the same channel experience too much pain. It’s reasonable to speculate that one of the reasons why people differ in their sensitivity to pain is due to genetic variation in how many of these receptors they express. Fortunately, there are drug treatments available that can block sodium channel 1.7, providing relief for those that experience extreme pain from even subtle stimuli.

Pain sensitivity has a genetic basis and there are things we can do to experience less pain. Additionally, we have maps of our body surface in our brain, called a homunculus, which is scaled in a way that matches sensitivity. The density of receptors in a body part is directly related to how much brain area is devoted to it. For example, the lips, fingertips, genitalia, eyes and area around the face have a huge representation, whereas the back, torso and less sensitive areas have smaller representations.

You can actually know how sensitive a given body part is and how much brain area is devoted to it through what’s called two-point discrimination. By performing this experiment, you can determine that areas of the body that have denser receptors are more sensitive to pain than others. This has direct bearing to pain as these areas tend to have more blood vessels and glia, which are the support cells, and other cells that lend to the inflammation response.

It is important to note that inflammation is not bad. In fact, it is a necessary part of the tissue repair response. We will discuss subjective and objective ways to modulate inflammation after tissue injury or even after too intense exercise.

Now you know why you have your Neurobiology of Somatosensation 101 under your belt. We didn’t cover everything, but we’ll touch on some of the other details as we go forward. It might be a nice time to think about the relationship between the periphery and the central maps in a way that many of you have probably heard about before, which is phantom limb pain.

For people who have had an arm, leg, finger, or some other portion of their body amputated, it is not uncommon to still feel as if they still have that limb or appendage intact. Typically, the sensation is not one of the limb being relaxed, but rather experiencing pain or contorted in the same orientation as it was around the time of the injury.

The reason for this is because the representation of the limb is still intact in the cortex, and it is trying to balance its levels of activity. Normally, it is getting proprioceptive feedback, which is our knowledge of where our limbs are in space, but since there is no proprioceptive feedback, the circuits start to ramp up their levels of activity and become very conscious of the phantom limb.

Before my lab was at Stanford, I was at UC San Diego and one of my colleagues was a guy, everyone just calls him by his last name, Ramachandran. Ramachandran is famous for understanding the phantom limb phenomenon and developing a very simple but very powerful solution to it. This solution speaks to the incredible capacity of top-down modulation, which is the ability to use one’s brain cognition and senses to control pain in the body. This is something that everyone, not just people missing limbs or in chronic pain, can learn to benefit from because it is a way to tap into our ability to use our mind to control perceptions of what’s happening in our body.

Ramachandran had people who were missing a limb put their intact limb into a box that had mirrors in it such that when they looked in the box and they moved their intact limb, the opposite limb, which was a reflection of the intact limb, would be seen as if it was intact. As they moved their intact limb, they would visualize with their eyes the limb that’s in the place of the absent limb. This is all done by mirrors moving around and they would feel immediate relief from the phantom pain. They would direct their hand toward a orientation that felt comfortable to them and then they would exit the mirror box and they would take their hand out, feeling as if the hand was now in its relaxed normal position. This allowed for real time remapping of the representation of the hand.

This is something that all of us would like to be able to do if we are in pain. If you stub your toe, break your ankle, take a hard fall on your bike or if you’re in chronic pain, wouldn’t it be amazing to be able to use a mind trick, but it’s not a trick because it’s real, visual imagery, to remap your representation of your body surface and where your body is.

We can all benefit from understanding pain better. This includes physical pain, as well as emotional pain. Ramachandran studies showed that plasticity can be driven by experience. For example, in cases of congenital deafness, a cochlear implant can restore hearing. Some people find this beneficial, while others do not.

Some deaf people would prefer not to hear anything, as it can be very disruptive to them. This might have to do with the need for further better engineering of these artificial cochleas. However, the brain is an adaptive device and it will respond to what you give it. It is able to take sensory inputs and make cognitive sense of them, and then interpret those signals. Pain is a perceptual thing as much as it is a physical thing and this has important relevance for healing different types of injury and the pain associated with that injury.

In people’s pursuit for neuroplasticity, a question that comes up is whether brushing teeth with the opposite hand for a couple of nights in a row will lead to neuroplasticity. The answer is probably yes. It is a deliberate action and focusing on it with an end goal will lead to errors, which are important signals for plasticity to happen. When the actions are correct, they are programmed in.

Brushing one’s teeth with the opposite hand is not the most effective use of plasticity, a phenomenon that allows us to adapt to changes in our environment. If, for whatever reason, it is important to do so, such as having a crowded bathroom, then it is fine. However, it is hard to imagine why this would be a highly adaptive behavior, unless one has an injured limb or is missing a limb.

Studies performed in the 1990s and 2000s have provided a solid base of data on how to overcome motor injury. This is especially important in cases of sprained ankles or broken arms, which can lead to muscle atrophy due to a lack of nerve activity.

Timothy Schallert and his graduate students and postdocs, including Theresa Jones, conducted research that can benefit those with injury, or those who want to balance out imbalances in motor activity. Right-handed people tend to be stronger in their left arm for compensatory reasons.

We can talk about handwriting later, but Schallert and colleagues showed that if there is damage to the brain or a limb, it is beneficial to restrict the use of the opposite, better-performing, uninjured limb. They had about a dozen papers showing that if there was damage centrally in the brain or there was damage to a limb, the thing to do is not to cast up the damaged side, but to restrict movement of the intact, uninjured opposite limb. This forces some movement in the injured limb and remarkably, through connections from the two sides of the brain, through the corpus callosum, this huge fiber pathway that links the two sides of the brain, they saw plasticity on both sides of the brain. This makes sense when you hear it: if I injure my left ankle and I’m limping along or using crutches, the last thing I want to do is injure my opposite limb or not use my opposite limb. By encouraging activity of the injured limb, provided it could be done without pain, and restricting the opposite, healthy part of the body, the speed of recovery was significantly faster.

Now I want to repeat: you don’t want to go injuring something further. That’s probably the worst thing you could do. However, in some cases where people have damage in their brain, the limbs are perfectly fine, but the motor signals aren’t getting down to the limbs. In that case, you actually are free to use either limb as much as you want, and you don’t want to rely on the uninjured pathway too much. In fact, you want to restrict the uninjured pathway.

Studies have found that the balance between the right and left side of our body is always dynamic, and even slight imbalances in the two sides of the body can get amplified. Therefore, when you’re in a situation where one side is injured or the brain is injured representing one side of the body, the key thing to do is to really overwork the side that needs the work and to restrict the activity of the side that doesn’t need the work because it’s healthy.

This has great semblance to ocular dominance plasticity, which was studied by Nobel Prize winning neurobiologists Torsten Wiesel and David Hubel. They showed that if one eye is closed early in development, the representation of the opposite eye in the brain is completely overtaken by the intact eye. This means that all of our senses and our movements are competing for space in our brain.

Therefore, anytime you’re injured and you’re hobbling along, you don’t want to injure yourself further, but you want to try and compensate in the ways that respect this competition for neural real estate. This usually means not relying on where you’re still strong because that’s just going to create runaway plasticity that’s going to make it very hard for you to recover the motor function and in some cases, the sensory function, of the damaged limb. Some may be wondering how long and how often one should restrict the activity of the intact or healthy limb, or limbs in some cases. The answer is you don’t have to do that all day, every day.

These experiments centered on doing one or two hours of dedicated work, such as sensory motor work. For instance, if you had a sprained ankle on the left, you might spend part of the day exercising your left leg, provided it’s not too painful, in a way that’s not damaging to the injury. This might be peddling unilaterally on a stationary bike or reaching, provided the shoulder is mobile, or even writing with the damaged side and intentionally not writing with the preferred or undamaged side. This has been shown to accelerate the central plasticity and the recovery of function, which is what most people want when they are injured – to get back to doing what they were doing previously without pain.

This brings up another topic related to neuroplasticity and injury – traumatic brain injury. Many injuries are not just about the limb and the lack of use of the limb but concussion and head injury. I want to emphasize that I’m not a neurologist, but I have many colleagues that are. We will do a whole month on TBI because it’s such a serious issue and it’s such a huge discussion. What is known about recovery from concussion is very important, as it has implications for normal aging, in terms of offsetting some of the cognitive and physical decline that occurs with age.

We shouldn’t think of TBI as just for the football players or just for the kids that had an injury or just for the person that was in the car accident. We want to learn about TBI and understand TBI for those folks, but we’re also going to talk about TBI as it relates to general degradation of brain function because there’s a certain resemblance there of TBI to general brain aging.

Typically after TBI, there are a number of different things that happen and there are a huge range of things that can create TBI. Neurologists and the emergency room physicians are going to want to know: was the skull itself injured or did the brain rattle around in the skull? Was there actually a breach through the skull? Is there a physical object in there? How many concussions has the person had?

Everyone’s situation with TBI is incredibly different, but there’s a constellation of symptoms that many people, if not all people with TBI, report which is headache, photophobia, that lights become aversive, sleep disruption, trouble concentrating, sometimes mood issues. There’s a huge range and of course the severity will vary, et cetera. In a previous episode, I mentioned the Kennard Principle.

The Kennard Principle, named after the famous neurologist Margaret Kennard, states that if you are going to get a brain injury, it is better to get it early in life than later. This is because the brain has a much greater capacity for repairing itself early in life than later. However, no one wants to get a traumatic brain injury (TBI). To avoid this, it is important to avoid activities that could lead to a TBI. Additionally, it is important to avoid a second traumatic brain injury or concussion. This is especially difficult for athletes, who often want to continue in their sport.

Those in the military or certain professions, such as construction, are also at risk for TBI due to the heavy objects that are swinging around in space. Wearing a hardhat helmet does not protect against these blunt forces or falls. For many, they have to go back to work in order to survive and feed their families. It is clear that the adult brain is mainly centered around the glymphatic system, which repairs the brain, regardless of when the TBI happened and how many times it has happened.

The brain was not previously thought to have a lymphatic system or circulating immune cells. However, about 10 years ago, the glymphatic system was discovered. This system is like a sewer system and it clears out debris that surrounds neurons, especially injured neurons. The glymphatic system is very active during sleep and has been imaged in functional magnetic resonance imaging. This system is important in clearing away the debris that sits between neurons and the cells that surround the connections between neurons, called the glia. These cells are actively involved in repairing the connections between neurons when damaged.

People with traumatic brain injuries (TBI) are advised to get adequate rest, as this is twofold advice. On the one hand, it is telling them to get sleep as all these good things happen in sleep. On the other hand, it is telling them to not continue to engage in their activity full time or really try to hammer through it. Most of the activity of the glymphatic system is occurring during slow-wave sleep, which typically happens in the early part of the evening. Even if someone is falling asleep and waking up three or four hours later, it is important to continue to get sleep. It is also important to note that the slow-wave sleep is mainly packed toward the early part of the night, in order to alleviate some of the anxiety of the 3:00 and 4:00 am wake up. However, it is important to follow protocols suggested by physicians in order to try and get regular, longer sleep of seven to eight hours.

The glymphatic system has been shown to be activated further in two ways. One is that sleeping on one side, not on back or stomach, seems to increase the amount of wash out or wash through of the glymphatic system. There aren’t a ton of data on this, but the data that exist are pretty solid. Again, sleeping on one side or with feet slightly elevated has been shown to increase the rate of clearance of some of the debris. This is because the way the glymphatic system works is it has a physical pressure fluid dynamic to it that allow it to work more efficiently when one is sleeping on their side or with feet slightly elevated.

To get the most out of the glymphatic system, it is recommended not to fall asleep in a chair while watching TV, but to sleep on one’s side, or if this is not possible, to sleep with feet slightly elevated. For example, I don’t like to sleep on my side, so I put a thin pillow under my ankles. Even though I don’t have TBI, I have had a few concussions before, and I find that putting the pillow under my ankles helps me sleep much more deeply and I wake up feeling much more refreshed.

It could be jogging.
It could be swimming.
It could be biking.

Exercise has been shown to improve the function of the glymphatic system, which helps with brain injury and general brain health. It is important to take the advice of a physician before beginning any exercise regimen. Studies have shown that doing 30-45 minutes of low-intensity cardio (such as walking, jogging, swimming, or biking) 3 times a week can improve the rates of clearance of debris after injury and accelerate the rates of flow for the glymphatic system. High-intensity interval training is great for those who are new to exercise, but it is important to remember that low-level cardio is the most effective way to improve brain health.

Exercise, especially Zone 2 type cardio, could be beneficial for washout of debris from the brain. This type of exercise is not designed to get your heart rate up to the point where you are improving your fitness levels, but rather to keep your brain healthy and to promote longevity. It could be jogging or cycling, provided it is safe for you given your brain state and injury state. It could also be combined with weight training and other forms of cardio. The hypothesized mechanism behind this is a molecule called aquaporin-4.

Aquaporin-4 is a molecule related to the glial system. Glia, which means “glue” in Latin, are the most numerous cells in the brain. They ensheath synapses and are very dynamic, like little ambulant cells. Microglia will run in and gather up debris and soak it up, then run out after an injury. Aquaporin-4 is mainly expressed by the glial cell called the astrocyte, which looks like a little star. Astrocytes bridge the connection between neurons, synapses, and the vasculature, blood system, and glymphatic system. They sit at the interface, like someone directing what to do at an emergency site. They also do some things more directly.

The glymphatic system and the glial astrocyte system is a system that we want chronically active throughout the day as much as possible. Low-level walking and Zone 2 cardio are recommended to maintain activity, and during slow-wave sleep is when this glymphatic system kicks in. This should be an actionable takeaway for everyone who cares about brain longevity, not just those trying to get over TBI.

Returning to the subjective aspects of pain modulation, our interpretation of a sensory event is immensely powerful for dictating our experience of the event. Combat sports and martial arts demonstrate how little a punch hurts during a fight, and how much more it hurts after the fight. This is due to the pain-blunting effects of adrenaline, which binds to particular receptors to shut down pain pathways. People who anticipate an injection of morphine also report a decrease in pain. This shows how powerful our interpretation can be.

Placebo effects and belief effects have a profound effect on our experience of noxious stimuli, such as pain. One study, conducted by Sean Mackey at Stanford, showed that people can adjust their pain response by looking at an image of a person they love, such as a romantic partner. Previous studies have also shown that the experience of pain is reduced and the threshold for pain is higher when people think about a person or thing they love, such as a pet.

People with a new relationship were able to tolerate more pain than those with an established relationship.
Research has shown that love can modulate pain, with the extent of the effect depending on how infatuated and obsessed someone is with the object of their love. Those who reported thinking about someone or a pet for many hours of the day and having an obsessive nature, such as what people might call codependency, were able to significantly reduce the pain they experienced. Interestingly, even if the other person didn’t know them, the feeling of love internally could still blunt the pain response. These effects were not small, and those with a new relationship were able to tolerate more pain than those with an established relationship.

For those of you who have been with your partners for many years and love them very much, you have a mechanism for blunting pain. These effects are major and are caused by top-down modulation, much like the mirror box experiments with phantom limb that relieve phantom pain. The opposite example is the nail through the boot which is a visual image that made the person think it was painful even though there was no tissue damage. This shows that the pain system is subject to perceptual influences.

The reason that infatuation and obsessive love can blunt the pain response and increase one’s threshold for pain may be due to dopamine release. This is distinct from the chemicals associated with warmth and connection, such as serotonin and oxytocin, which tend to be for more stable, long-lasting relationships. Dopamine is what dilates the pupils and gets people really excited.

People can’t stop thinking about someone and the text messages they send and receive are exciting. They can’t wait for the response and the anticipation of the “dot dot dot” on the screen is excruciating. When they don’t respond for two minutes, people start to get anxious. While I’m not here to support that kind of behavior, I do believe that this obsessive type of love, which is associated with the dopamine pathway, can be useful in reducing the unpleasantness of physical pain. It can also be used to reduce the unpleasantness of everyday tasks, such as sitting in traffic. Emotional pain and physical pain become so intertwined that they start to become one in the same. Therefore, if love and infatuation can reduce pain by releasing dopamine, could dopamine release itself blunt pain? Could we use it to treat chronic and acute pain?

We’re going to talk about something quite different which is putting needles and electricity in different parts of the body, so-called acupuncture. This has been viewed as an alternative medicine, but now there are excellent laboratories exploring what’s called electroacupuncture and acupuncture. Professor Qiufu Ma at Harvard Medical School is a source of information and his papers stand behind the information provided.

Rigorous variable-isolating experiments have been used to understand how acupuncture works. It can both exacerbate and relieve pain through discrete pathways that can be traced back to dopamine and chemicals and neural circuits that give rise to perceptions of pain, love and other experiences.

In a previous podcast episode, I mentioned my experience of visiting an acupuncturist and getting acupuncture. The acupuncture itself didn’t do much for me, but I wasn’t there for any specific reason. I’m not passing judgment on acupuncture.

I know a number of people who really derive tremendous benefit from acupuncture for pain and gastrointestinal issues. There are good peer-reviewed studies supporting the use of acupuncture for GI tract issues. In recent years, there has been an emphasis on trying to understand the mechanism of things like acupuncture, not to support it, but as a way to understand how these practices might benefit people who are experiencing pain or how it changes the nervous system and brain-body relationship. The National Institutes of Health in the United States now has a subdivision, an institute within the National Institutes of Health, called Complementary Health, which is interested in things like acupuncture.

I want to talk about the incredible way in which acupuncture illuminates the crosstalk between the somatosensory system (our ability to feel stuff externally and internally) and the autonomic nervous system that regulates our levels of alertness or calmness. I’ll also discuss how acupuncture points to relief for referred pain. This brings us to the homunculus, which is a representation of our body surface in our brain. This representation is called somatotopic, meaning that areas of the body that are near one another (like the thumb and forefinger) are represented by neurons that are nearby each other in the brain.

You might say, “Well, duh,” but actually, it didn’t have to be that way. The neurons that represent the tip of my forefinger and the neurons that represent my thumb on the same hand could have been distantly located and therefore the map of my body surface, the homunculus, would be really disordered. However, it is very ordered and smooth. When stimulating my forefinger and then marching that stimulation across my finger, across the palm and to the nearby thumb, neurons in the brain form a sort of J shape in their pattern of activation. This is known as somatotopy. The connections from those brain neurons are sent into the body and they are synchronized with input from the viscera, from our guts, from our diaphragm, from our stomach, from our spleen, from our heart. Our internal organs are sending information up to this map in our brain of the body surface, which is about internal information, or interoception, our ability to look inside or imagine inside and feel what we’re feeling inside.

Acupuncture involves taking needles, and sometimes electricity and or heat as well, and stimulating particular locations on the body. Through these maps of stimulation that have been developed over thousands of years, mostly in Asia, they have these maps that speak to, if you stimulate this part of the body, you get this response. For example, if somebody has a gastrointestinal issue, like their guts are moving too quick, they have diarrhea, you stimulate this area and it’ll slow their gut motility down, or if their gut motility is too slow, they’re constipated, you stimulate someplace else and it accelerates it. To a Westerner who’s not thinking about the underlying neural circuitry, it could sound kind of wacky.

Qiufu Ma’s lab at Harvard Medical School has been exploring how stimulation of different types, with heat or without heat, on different parts of the body can modulate pain and inflammation. In a particularly exciting study, they showed that stimulation of the abdomen, anywhere on the midsection, weakly does nothing. However, intense stimulation of the abdomen with electroacupuncture has a very strong effect of increasing inflammation in the body. This is important to understand because it activates a particular nerve pathway, the splenic spinal sympathetic axis, which is pro-inflammatory under most conditions. However, there are other conditions where this can be beneficial, such as when the person is dealing with a particular bacterial infection. Qiufu’s lab also showed that stimulation of the feet and hands can reduce inflammation, and this was done mechanistically by blocking certain pathways with the appropriate control experiments.

Researchers have measured molecules such as IL-6 and cytokines related to the inflammation response and found that low intensity stimulation of the hind limbs led to increased activity of the vagus nerve. The vagus nerve is the tenth cranial nerve and serves the rest and digest and parasympathetic, or calming, response. This suggests that the effects of acupuncture depend on the intensity of the stimulation and the area of the body where it is applied.

The stimulation of the abdomen and other areas can be pro-inflammatory because it triggers certain loops that go back to the brain and activate anxiety pathways, exacerbating pain. In contrast, intense stimulation of certain areas can stimulate norepinephrine and blunt pain. This is due to the release of norepinephrine and epinephrine from the adrenal gland, which binds to beta noradrenergic receptors. This activates the spleen, releasing cells to combat infection and provide an anti-inflammatory response.

Well, they don’t heal because they don’t have inflammation.

Putting all this together, we can see that there is a real map of our body surface that when stimulated communicates with our autonomic nervous system. This system controls alertness or calmness and releases molecules like norepinephrine and dopamine which make us more alert and blunt our response to pain and reduce inflammation. However, there are other pathways that when stimulated are pro-inflammatory.

Inflammation is essential to heal from any injury and acute inflammation is absolutely essential. Chronic inflammation is bad, but acute inflammation is necessary. People with mutations in receptors for sensing pain don’t heal because they don’t have inflammation.

People with joint issues often lack the inflammation response, which can be beneficial. There is a lot of interest in limiting inflammation, and one of the most popular methods is turmeric, though I am skeptical. A study from Stanford and other universities showed that a lot of turmeric is contaminated with lead. Additionally, for men in particular, turmeric can be antagonistic to dihydrotestosterone.

Dihydrotestosterone is the more dominant form of androgen in human males and is involved in things like aggression and libido. Many people who have taken turmeric report a severe blunting of affect and libido, which may be a serious negative. For this reason, I avoid turmeric.

I believe that inflammation response is a healthy response, although it needs to be kept in check. We have pathways in our body specifically to increase inflammation, and it is only when inflammation goes unchecked that it becomes problematic for repair and can exacerbate certain forms of dementia. I would like to create more nuance in the conversation around inflammation, as people have taken the discussion to mean that all inflammation is bad.

Before continuing, I wanted to answer a question I get a lot: what about Wim Hof breathing?

Wim Hof, also known as The Iceman, has developed a breathing technique similar to Tummo breathing. It involves hyperventilating followed by exhales and breath holds. It is important to note that this technique should never be done near water, as people have drowned while attempting it. I am not here to either promote or discourage it, but it is important to consider the net effect.

A number of people have asked me about it in relation to pain management. This breathing technique liberates adrenaline from the adrenals, which can be used to counter infection and stress. This is supported by a paper published in the “Proceedings of the National Academy of Sciences” which showed that the breathing pattern can counter infection from endotoxin. Stress does not necessarily lead to infection, as is often thought.

Stress can counter infection by liberating killer cells in the body. However, you don’t want the stress response to stay on indefinitely. Practices such as Wim Hof breathing and taking ice baths can help to release adrenaline and counter the infection, but it’s important to regulate the duration of the adrenaline response. This makes sense when considering our species’ evolution under conditions of famine and cold. For example, in Texas right now, there are many people suffering from the extreme cold and power outages. Their bodies are releasing a lot of adrenaline as they are cold and potentially hungry.

They’re probably stressed due to the lack of heat. This is leading to the release of adrenaline which is helping to keep them safe from infection. Once they get their heat back on and they can relax and warm up again, hopefully by the time this podcast comes out, they will have already recovered. Stress and inflammation can be caused by a number of things, such as cold, hyperventilation, physical threats, exams, or upcoming surgeries. The adrenaline response and the inflammation that comes with it is adaptive and highly adaptive.

Short-term plasticity is designed to make us better for what we’re experiencing and challenged with, not worse. This adds an additional layer to the idea that stress, inflammation, and other similar things are bad. I’m not suggesting people do or don’t do something like Wim Hof or Tummo breathing, I just want to point to their utility. Every episode, I want to provide listeners with knowledge and actionable tools. Today, we’ve talked about a variety of tools, but I want to focus on a particular sequence of tools that can help manage injury, recover, and heal as fast as possible. This includes removing the pain, getting mobility back, and getting back to a normal life. This sequence was developed in close consultation with Kelly Starrett, a formally trained exercise physiologist who can be found at The Ready State.

Kelly is a world expert in movement and tissue rehabilitation. He is not a sponsor of the podcast, but is a friend and colleague that I trust. His views on tissue rehabilitation and injury are well-grounded in medicine, physiology, and the cutting edge of new advice. It is important to consult with a physician before adopting any protocols.

I asked Kelly what the absolute necessary things to do in the case of a sprain, break, injury, ACL tear, or shoulder injury are, and what science these are grounded in. After finding the studies that either supported or refuted his advice, I found that sleep is essential. We agreed that eight hours minimum in bed per night is critical, although it does not have to be eight hours of sleep. We also acknowledged that the conditions of our sleeping can impact these injuries.

Kelly and I agreed that eight hours of sleep would be ideal, but if not, at least eight hours of immobility. We have provided links to non-sleep deep rest protocols before and more are coming soon. This is a non-negotiable in terms of allowing for glymphatic clearance and tissue clearance. Additionally, a 10-minute walk per day (unless it is excruciating or impossible) is recommended.

I was taught to use ice on an injury, but speaking to exercise physiologists and physicians, I learned that it is more of a placebo and can create sludging within the blood and lymphatic tissue. Heat is actually quite beneficial, as it allows macrophages and other cell types to phagocytose debris and move it out of the injury site, so that it can repair.

Heat shock proteins have very little data to support the idea that they are part of the wound healing process, at least in terms of conventional heat such as hot water bottles, hot baths, or hot compresses. The major effects seem to be explained by heat improving the viscosity of tissues, as well as the clearance and perfusion of fluids, such as blood, lymph, and other fluids, out of the injury area.

When a kid gets injured in soccer, they are usually given an ice pack to reduce pain. The consensus now is that the ice pack is more of a top-down modulation, and there have been studies that have shown the placebo effect of the ice pack. Thus, ice packs may only be a placebo.

Heat may be beneficial for reducing pain in both the short and long run compared to cold or ice. This is because cooling shuts down the nerve, and when the nerve heats back up, it becomes hyperactive, which can lead to greater pain. In terms of chronic pain, it is thought to be plasticity gone wrong, similar to PTSD for the emotional system. To help with chronic pain, a number of different protocols may be used to rewire the brain and peripheral centers associated with the pain. Fibromyalgia, which is whole-body pain, may be related to too little inhibition.

In the brain, you have excitation and inhibition which come from different sources of neurons. The inhibition is mainly from GABA and glycine. In fibromyalgia, there is too little central modulation of the pain responses within the brain, so that people experience whole-body pain. Emerging therapies to address this issue are interesting; for example, red light therapy. This is typically talked about in terms of mitochondria, however, the data on this are not so terrific, except for one study from Glen Jeffery’s lab at University College London, showing that red light stimulation to the eyes in people 40 or older can offset some of the effects of macular degeneration. People with fibromyalgia are now starting to use red light therapies. Experts in pain suggest that red light local therapy may have some effect, but the systemic red light therapy (such as wearing protection to the eyes) may be approximating the effects of nature, like a surrogate technology for getting outside in the sunshine.

Sunlight may have as much or more effect than red light therapies when it comes to wound healing. Depending on the neighborhood you live in, exposing your body to sunlight may or may not be a weird thing to do. Other factors to consider for wound healing are movement, heat, light, sleep, and in some cases the use of restricting above and below the injury to then release and increase perfusion. Common treatments for wound healing, such as non-steroid anti-inflammatory drugs, work by blocking things in the COX prostaglandin pathway. This may reduce inflammation and pain, but may not be so great at the beginning when inflammation is necessary. The principles that Qiufu Ma’s lab has found with acupuncture can also be applied to wound healing.

The immediate acute inflammation response is good. It calls to the site of injury things that are going to clean up the injury and bad cells. To improve perfusion, the glymphatic system, getting deep sleep, feet elevated, sleeping on one side and low-level Zone 2 cardio three times a week can be useful. Red light and sunlight can also be beneficial, although the latter depends on who you talk to. Stem cells exist in all of us during development, and we were created from them. Cells then become restricted in their lineage, so a skin cell can’t be turned into a neuron, unless you do some fancy molecular gymnastics to it. Yamanaka won the Nobel Prize for finding these Yamanaka factors which can turn a skin cell into a neuron, but this is not an approved therapy at this time. Many people also ask about platelet-rich plasma (PRP) where they take blood, enrich it for platelets and re-inject it back into people.

Here’s the deal: It has never been shown whether or not the injection itself is what’s actually creating the effect. This is something that the acupuncture literature suffered from for a long time. A sham control is when you do everything exactly the same way you would, but you don’t actually poke the needle into the skin. With a drug treatment, you would inject a drug into a person and then the control would be that you would bring the injection over, but not actually do the injection.

It’s never really been shown whether or not PRP has effects that are separate from injecting a volume of fluid into a tissue. The claims that PRP actually contains stem cells are very feeble and when you look at the literature and talk to experts in the stem cell field, they will tell you that the number of stem cells in PRP is infinitesimally small. In fact, places that inject PRP for injuries are not allowed to advertise through the use of the words stem cells.

Stem cells are an exciting area of technology; however, it is currently illegal in the United States. A clinic in Florida was shut down a couple of years ago for injecting stem cells harvested from patients into the eye for macular degeneration. These patients suffered from poor vision and went completely blind shortly after the injection. Due to this, I am very skeptical of stem cell treatment work that is out there. It is very hard to get in the United States as it is not approved, and the marketing around PRP treatments is shaky at best.

I’m sure a number of people will say that they had PRP and benefited from it tremendously and I don’t doubt that. Whether or not it was placebo, today we talked a lot about top-down control, that’s just a variant on the word placebo, belief effects, whether or not it was placebo or not, I don’t know. I wasn’t there. That’s for you to decide and I’m not here to tell you that you should or shouldn’t do something, but I do think that anything involving stem cells, one should be very cautious of.

You should also be very cautious of anyone that tells you that PRP is injecting a lot of stem cells. This is an evolving area that really needs a lot more work and attention. The major issue with stem cells that I think is concerning is that stem cells are cells that want to become lots of different things, not just the tissue that you’re interested in.

If you damage your knee and you inject stem cells into your knee, you need to molecularly restrict those stem cells so that they don’t become tumor cells. A tumor is a collection of stem cells. When you get something horrible like glioblastoma in the brain, which is a terrible thing to have, it’s glial cells that returned to stemness, excessive stemness, they’ve started to produce too many of themselves, and glioblastoma is often deadly, not always.

Stem cell injections are an exciting technology, and one that many people would like to explore. However, extreme caution should be taken when considering this type of treatment, even if the stem cells come from the patient’s own blood. The technology is developing, and those interested should be sure to research the evidence and outcomes of PRP treatments. Ultimately, it is up to the individual to decide if they want to pursue this type of treatment, but it is important to be informed. When considering tissue recovery and injury, Kelly and his coworkers at The Ready State have some valuable insights.

It’s phenomenal that they have worked with all the top people in just about every domain of life, it seems. Very high-integrity folks. Some of you may not be injured, athletes, or wanting stem cell injections, so I’m suggesting to hold off until the field learns more about how to do that safely.

I want to talk about an interesting and somewhat weird technology, which is baby blood. I have a colleague at Stanford, Tony Wyss-Coray, and in 2014 his laboratory published a study showing that the blood of young rodents, mice and rats, when transfused into old, demented rodents, mice and rats, made those old, demented rodents recover much of their memory and seem much more vital and energetic. Better recall of different spatial learning tasks, tissue and wound healing have since been shown to be improved in these older animals. It’s pretty incredible.

They went on to show several years later that blood from umbilical cords can do the same and this is the basis of a biotech company. Actually, one of my former postdocs is now an employee there. They’ve isolated the molecules from young blood that seems to vitalize or revitalize the old brain and body, and one of those molecules goes by the name TIMP2 (T-I-M-P-2).

Where’s all this going? Well, I don’t know how long it’s going to be before there are treatments based on these blood transfusions. I doubt that blood transfusions themselves from young people into old people is going to be used for the treatment of dementia, although it might, as weird as it seems. We know that transfusions of all sorts of stuff, for instance, fecal transplants are being used to treat obesity. The gut microbiome of thin people is being, not transfused, but is being transplanted into the colons and guts of obese people and leading to weight loss, which sounds really wild and is not a topic I particularly enjoy talking about, but nonetheless, it points to the importance of the gut microbiome in regulating things like blood sugar and health as it relates to obesity and diabetes and all sorts of things.

It does appear that there are things, factors in the blood of young members of a given species that are lost over time in the older members of that species.

I’m not going to give you a tool on the basis of these findings today. I am not going to tell you to consume any fluid from any other member of your species, our species, for any reason. However, it is important to mention that the science is asking questions such as what are the factors within the brain that allow the young brain to recover so much better than the older brain from injury, from all sorts of things, events, et cetera. Additionally, what are the factors in the older brain that are limiting? Thinking about identifying which factors are going to allow people to restore cognitive function, physical function, wound healing and so forth is a really exciting area.

I have talked about a lot of tools today. These include somatosensation, plasticity, pain, acupuncture, nuance of acupuncture, inflammation and stress, high-intensity breathing, restricting limb movement to get compensatory regrowth of pathways, and reactivation of pathways that have been injured or damaged. As always, we take a whirlwind tour through a given topic, laying down some tools as we go.

Today I would like to talk about the principles that relate to pain and injury, as well as neuroplasticity in general, in the context of the somatosensory system. I hope this information will be of use to all of you, although I don’t wish injury on anyone. I do hope that you will keep this information in mind if ever you find yourself in a situation where you have to ask what’s the difference between my perception and the actual tissue damage? Is injury and pain the same? Well, no. Do I have some control over my experience of pain? Absolutely. Does this involve taking drugs or doing certain therapeutics? No, not necessarily. There is a subjective component, as well as a need sometimes to treat the injury at the level of the pain receptors at the site of the wound. I encourage you to take the information and do with it what you will. Thank you for your time and attention.

Thank you for your time and attention today! Please subscribe to our YouTube channel, Apple, and Spotify. Leave us comments and feedback, and give us a five star review on Apple if you think we deserve it. Additionally, check out our sponsors and Patreon page at patreon.com/andrewhuberman. If you are interested in the supplements I take, you can visit Thorne at thorne.com/u/huberman and get 20% off any of the listed supplements or any others on the Thorne site. As always, thank you for your interest in science. [relaxing rock music]