Healing

Healing is one important thing that is mostly ignored by the modern medicine. Our bodies have an amazing ability to heal and we should do everything we can to support healing. One example where healing is extremely important is the spine. Most of my patients suffer from spine issues. The first question we should ask is why they have the issue in the first place? Why is the tissue quality not good enough? Why was the pressure on the disc or the spine joint high enough to cause an issue? And if the issue occurred why it did not heal in a timely manner? Very few patients and medical providers ask any of these questions. One spine surgeon actually quit doing spine surgery after he realized that he needs to think about these questions: youtube link.

Many people just want a fix for their spine. And you cannot blame them for this. The modern medicine is selling surgeries as a fix. What most patients do not realize is that the healing after the surgery is more important than the surgery itself. There is a great quote by the surgeon John Mulholland in the book "The body electric" (by Robert Becker): "The surgeon can cut, remove or rearrange the tissues, and sew up the wound, but only the patient can do the healing. Surgeons must always be humble before this miracle. We must treat the tissues with sure, deft gentleness, and above all we must do no harm, for we are nothing more than nature's assistants." Also a surgery does not fix the root cause of the problem. The root causes persist creating the same issues all over again.

The modern medicine teaches people that there is only one way in life: your body will break down and you will need medications and surgeries. What is rarely mentioned is that we have a very poor understanding of the human body and biology in general. Sometimes I tell my patients that if you take the smartest 100 scientists in the country they are not as smart as their own bodies. All these scientists have no clue how to build a human body starting from one cell. Our bodies did build themselves. And our bodies also know how to heal. All we need to do is to give our bodies the right ingredients: proper food, movement, social life and the right mindset.

Consciousness

Consciousness was one reason I got interested in neuroscience 20 years ago. After graduating with a PhD in neuroscience in 2011 I felt I knew just a little more. Over the last couple of years I read extensively about different psychotherapy approaches and pretty much ignored the science about consciousness. Out of the psychotherapy approaches the most interesting ones were internal family systems and psychedelic assisted psychotherapy. Over the last 6 months I came across the research by Michael Levin in bioelectricity. After listening to tens of hours of presentations and podcast episodes with Michael Levin I realized that he actually has some interesting ideas about consciousness. He thinks that cognition (and maybe consciousness) is a property of the cells in general and that neurons are not special. I agree with the assessment that cognition is likely universal. The implications are pretty profound. It is very likely that our organs have some level of cognition. Also it seems that in the brain there are multiple conscious agents that interact with each other. Only one or some of these conscious agents have access to the language module. The other agents manifest in other ways: maybe movement, emotions, writing…. The psychological approaches mentioned earlier (e.g internal family systems and psychedelic assisted psychotherapy) facilitate a discussion between these conscious agents. Meditation is another way to get access to these agents. Currently in psychology there is a separation between consciousness (the conscious agent(s) with access to language) and the subconscious level (the conscious agents without access to language). I feel that this separation is misleading. In my opinion all these agents are conscious.

Nature is full of examples where even simple cells are capable of making amazing decisions. This is an interesting experiment: youtube link

I will spend the next year thinking and reading on this topic. I have a book list already.

Personal development

Every year I set the goal to read about a certain topic. So far I spent a year or so reading about food, mind and movement. This year I am reading about bioelectricity. Over the last 3-4 years I learned way more than they taught me during my education. I am applying this knowledge to myself, my family and my patients.

One of my favorite athletes is Novak Djokovic. I am reading a book written by his doctor: Igor Cetojevic. The following quote is really good:

“When I was studying in China a doctor told me, "In the West when you go to a doctor, they ask you about your family history. "Did your parents suffer from any particular disease, for example?" Here in China often the patients ask me, “Is your family healthy? Are you in good health?” If I can't keep myself and my family in good health why should a person put his life in my hands."”

Revolutionary ideas

Once in a while I come across ideas that are truly mind blowing. I remember that in 2008 I read an article in the New Scientist about tunneling nanotubes. I was super excited that a new form of intercellular communication was discovered. It took a long time to become accepted.

About 1-2 years ago I listened to a podcast episode with Michael Levin and his name stuck in my mind. Two weeks ago I remembered about him and looked him up. I could not stop reading and thinking about his research. Michael Levin and his collaborators discovered a new layer (bioelectricity) above the DNA/cell hardware level. The implications are massive from tissue regeneration to cancer treatment and philosophy (what is consciousness). His website is an amazing resource. I am not sure when he has time to do actual research because he gives tons of presentations and is a guest on many podcasts.

Some of his presentations:

https://www.youtube.com/watch?v=SRV1oLRXeE4

https://go.ted.com/michaellevin

Prevention of Alzheimer's disease

A lot of news recently about new medications to treat Alzheimer's disease. I think more focus should be on the prevention of dementia. This is a figure about modifiable factors to prevent dementia. It is estimated that modifiable factors contribute to about 40% of the risk of dementia. Improving these risk factors also helps pretty much everything else in the body. The figure is from this article:
https://www.ncbi.nlm.nih.gov/pmc/articles/

Food as fuel for the body

I think most of us forget that the role of food is actually to be fuel for the body. The food industry is just trying to confuse us and they use all kind of tricks to make us buy their products. The reality is that we have a very good idea what is the right fuel for us. For most of the human history we ate simple fresh foods and our body evolved to function the best with this type of fuel. The best is to eat foods that are in season with maybe the one exception being the vegetables.

The food industry confused us to such a degree that common sense does not apply to food anymore. For example, in diabetes (which affects 1 in 10 adults in US) carbohydrates increase blood glucose. The common sense would be to avoid carbohydrates in diet, but the food industry convinced everybody (including medical professionals) that we need just to set some arbitrary limits for carbohydrate intake in diabetes. Imagine that you put diesel into your gas engine car and then you go to your mechanic. The mechanic is going to fix your car first time. But you put diesel again and again. By the third or forth time the mechanic will just give up. Also the mechanic is never going to tell you just to just add less diesel into your gas car. In diabetes we lost our common sense and the medical professionals just tell people to use the wrong fuel (carbohydrates) but relatively not too much of it. And then the medical professionals just keep patching the engines (various organs) damaged by uncontrolled diabetes day after day…

One of the organs that is greatly affected by the wrong fuel is the liver. Our livers are the first stop for the digested ingredients in the food. According to the paper by Younossi Z et. al. Hepatology. 2019: “Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death.”

Part of the problem in US is that we never had a unitary food culture. This is a theory described in the book “The omnivore’s dilemma” by Michael Pollan. According to Michael Pollan: “So violent a change in a culture’s eating habits is surely the sign of a national eating disorder. Certainly it would never have happened in a culture in possession of deeply rooted traditions surrounding food and eating. But then, such a culture would not feel the need for its most august legislative body to ever deliberate the nation’s “dietary goals”—or, for that matter, to wage political battle every few years over the precise design of an official government graphic called the “food pyramid.””

Eating simple fresh foods can prevent a lot of diseases. But once you got a disease a great effort needs to be done to reverse the disease. The sickest somebody is the biggest the effort required. For example, in diabetes type 2 related to obesity things have been going badly for so many years that it will take years to reverse it with a very strict dietary approach. And maybe the metabolism will never be back to healthy level in people with long standing diabetes. But at least we have to try.

How to improve health, pain and eveything else - 2022 edition

Since graduating from my pain fellowship 6 years ago I have been thinking about how to help my patients achieve pain relief and better health. In the big picture the things that make us sick are: our genes, our behavior, our environment and time. We cannot change our genes yet and even when we can do it I will not sign up for the first wave of gene therapies. We definitely cannot change time. So we are left with our behavior and our environment. From a behavior perspective I think we knew the basics for a very long time, but somehow we forgot what is truly important. In my opinion there are three levels we should be thinking about.
1. Metabolic health. I wrote a blog post about this last year. Basically, the metabolic health is closely related to our diet. My advice is to eat whole foods, lots of vegetables, avoid excessive fruit intake (especially grapes and other very sweet fruits). Stay away from sugar/fructose, fruit juices and processed foods. The goal of the food industry is to sell us stuff and they create super addictive foods. Billions of dollars are spent on creating and advertising foods that make us sick long term. The food industry is so good at getting us sick that it takes only 10-20 years to accomplish this. Just look at the children, they are getting obese and metabolically sick at very high rates. It is estimated that 19.7% of American children and adolescents (2-19 years old) are obese according to CDC. One study estimated that only 12% of the US adult population is metabolically healthy. The effort to improve metabolic health needs to be even greater for people with serious metabolic disturbances like diabetes. In addition to everything mentioned so far people with diabetes should look into a low carbohydrate diet.
2. Movement. Most of us don’t move as much as our ancestors. I am reading the book: “The practice of natural movement” by Erwan Le Corre. In Erwan’s opinion many of us are by choice zoo animals. We limit our movements and our environment so much that we are nowhere close to our ancestors in terms of movement type and frequency. Our children have the instinct of our ancestors and practice all kind of movements by crawling, jumping, climbing everything they can find. But we then restrict what children can do and we put them in chairs at desks. For many people the only movement they do is walking from one chair/couch to another. In my opinion the best is to return to a whole range of movements using as many muscles as possible. One step in that direction is yoga or tai-chi. If you have children around, try to do whatever they do. If you see physical therapists, ask them how they are going help you improve your whole body.
3. Mental health. Our minds are amazing tools but we need to use them properly for our benefit. We should give our minds as much attention as we give to our bodies. A daily practice of mind exercises like meditation can unlock deep levels of the mind. Everybody carries around a certain level of baggage from the past: e.g. traumas big and small. The good news is that we can heal the past. For significant trauma leading to PTSD and depression I think an option in the near future will be psychedelic therapy. Tim Ferris had a good podcast episode and the book “The fellowship of the river” by Joseph Tafur is a good resource. For chronic pain therapies targeting emotions (e.g EAET and PRC) are more successful than the standard cognitive behavioral therapy.

Another important area is sleep. I wrote a blog post about sleep a few years ago. In my experience if we improve metabolic health and mental health, sleep gets better. But we should not ignore sleep hygiene.

We will probably have little use of the modern medicine outside acute conditions if people master all these levels of health.

Interesting readings

I usually write about the podcasts that I have been listening to every year. This year I don’t have any new podcasts. But I found a really good journal: Philosophical Transactions B of the Royal Society. For each issue they have a theme and most articles are free/open access. The issues discussing: “Systems neuroscience through the lens of evolutionary theory” and “Perceptual consciousness and cognitive access” are outstanding.

Predictive coding and chronic pain

One of my first posts on this blog in 2018 was about brain tricks. Four years later there is way more information about the role of predictive coding in different conditions, including chronic pain. Some of the researchers involved in this are: Tor Wager, Mick Thacker and Zhe S Chen. The idea is that there is a top down processing of pain in various areas of the nervous system and a bottom up flow of information from the periphery to the brain. The ultimate goal of the humans is to survive and predicting future events increases the chance of survival. The best way to look at pain is to consider pain as a danger signal. Sometimes the nervous system gets stuck in predicting pain when there is no actual threat. The theory is that the prediction is so strong that it does not matter what signals are coming from the body.

In my opinion it is not only that the prediction happens but also the body is affected. There is a prediction error generated whenever the prediction does not match the actual input from the body. I don’t think prediction errors are tolerated in the nervous system for long periods of time. So the options are either change the prediction or change the input. The prediction obviously does not change as long as there is chronic pain. Then the only option is that the input changes. Our nervous system has amazing control over the body. I think it is reasonable to assume that the brain can actually change the input to match the prediction in chronic pain through a variety of mechanisms (e.g. autonomic nervous system and immune system). There is a paper by Moseley et. al. in which they show that an illusion of the hand location in complex regional pain syndrome can change the temperature of the hand. Asya Rolls has published articles showing the connection between the brain and the immune system. In one paper by Koren et al. they show that an inflammation in the colon activates certain brain areas and then activating the same brain areas can create inflammation in the colon. In the end it is likely that there is both a body and a nervous system problem in chronic pain. But the cause is probably the nervous system.

The best way to change the prediction is actually psychotherapy: see the work of Howard Schubiner. The psychological approaches are pain reprocessing therapy (PRT) and if needed, emotional awareness and expression therapy (EAET). In the real word it is a little hard to convince patients with chronic pain to explore the psychological approaches that can significantly improve or even cure their chronic pain. Our society is so focused on structural problems that we have become oblivious to the role of the brain/nervous system.

There are also ways to affect the bottom up information. For example, movement therapies like physical therapy, yoga, tai-chi can change the actual peripheral information. There is a chance that the weight of this bottom up information will increase over time when compared to the prediction. Slowly the prediction will move closer to the now improved peripheral information and chronic pain disappears.

Plantar fasciitis

Plantar fasciits is a common problem that affects 1 in 10 people during their life time (Am Fam Physician article). I have a few people that I trust when it comes to feet. One of them is Mark Cucuzzella who is a family medicine doctor and a runner. Mark Cucuzzella and a few other practitioners put together a handbook about how to treat plantar fasciitis naturally: link

Other good resources about feet are Irene Davis and Daniel Lieberman who are researchers at Harvard. They are involved in research in biomechanics and are proponents of minimalist shoes and barefoot running. This lecture called “An evolutionary medical perspective on shoes” by Daniel Lieberman is very entertaining.

Metabolic health

It is estimated that only 12% of the US adult population is metabolically healthy (source). Over the last year I have been working to improve the metabolic health of my patients as part of the chronic pain treatment. The success has been variable, but I have seen dramatic results in some patients.

Recently I started to read the book “Metabolical” by Robert Lustig. This book contains some errors and his style might not be for everyone, but overall it is an excellent resource for understanding metabolic health. He proposes eight molecular pathways that can be altered in metabolic diseases:
1. Glycation - determined by glucose level
2. Oxidative stress
3. Mitochondrial dysfunction
4. Insulin resistance
5. Membrane Integrity
6. Inflammation
7. Epigenetics
8. Autophagy

In our clinical practice we cannot easily assess the molecular pathways, but we can get some idea from the vital signs and lab work. I recommend everybody to be involved in their own care because that is the only way to understand the significance of metabolic health.

Labs:

- Lipid profile (LDL-C, HDL-C, Triglycerides). The one I look at first is the triglycerides. The goal should be below 150 mg/dl (even better if under 100). Most common causes of increased triglycerides are sugar/fructose and alcohol. LDL cholesterol (the so called bad cholesterol) is a complicated topic because there are different types of LDL and these are not assessed on the regular labs.
- Homocysteine level – high levels (over 15) might be due to folic acid deficiency
- Alanine aminotransferase and aspartate aminotransferase (ALT and AST). ALT needs to be below 25. If ALT is elevated then we need to measure GGT. If GGT is over 35 then likely there is a need for liver ultrasound to assess the liver fat. Fatty liver can lead to NASH (nonalcoholic steatohepatitis) which is the leading cause of liver transplant in US. Sadly, the children have fatty liver at alarming levels: one study estimated that about 1 in 4 obese children has fatty liver disease (source). Other studies put the prevalence of fatty liver at even higher levels in obese children.
- Uric acid – goal is below 5.5. This podcast episode is a really good discussion about uric acid.
- Fasting insulin – if above 15 microunits/ml then insulin resistance. Obesity is the most common cause of insulin resistance.
- Fasting glucose
- Hemoglobin A1c – aim for close to 5%. The medical system has decided that hemoglobin A1C of 7% is good enough, but this is far from optimal. The goal of 7% was chosen because it is really difficult to safely decrease hemoglobin A1C to normal levels with medications. The only way to normalize hemoglobin A1C is diet.

Podcasts 2021

Over the last few months I spent many hours listening to the following podcasts:

Theories of Everything with Curt Jaimungal - some of the episodes I really enjoyed: Donald Hoffman, Karl Friston and Anil Seth

Thoughts on Record - some of the episodes I really enjoyed: Joseph LeDoux, Lisa Feldman Barrett, Charles Raison, Howard Schubiner and Allan Abbass

Mental health

According to the the World Health Organization mental health is a state of well-being in which an individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and is able to make a contribution to his or her community.

In my opinion everybody should do everything in their power to achieve the best mental health possible. Physical health is far from enough if you do not have good mental health. There area many therapies available for improvement of mental health depending on the needs. In my field of chronic pain the following options are available:
1. Cognitive behavioral therapy (CBT). This is by far the most popular therapy in chronic pain and psychiatric diseases. Some information from the American Psychological Association here.
2. Acceptance and commitment therapy (ACT). A good lecture by Lilian Dindo here. Steven Hayes is an important figure in this field.
3. Internal Family Systems (IFS). A good introduction is this podcast episode with Tim Ferris and Richard Schwartz. This is a fascinating article about using IFS in chronic pain. More information in this post on Medium.

Any discussion about chronic pain and psychology should also include John Sarno. He helped thousands of people heal their chronic pain. A good lecture about his method by Ira Raschbaum here. For some people just reading his books completely resolved their long lasting pain.

One very debilitating condition is post-traumatic stress disorder (PTSD). There is a really good hope that psychotherapy combined with psychedelics is going to provide the most successful treatment soon. An overview in this podcast episode with Tim Ferris and Rick Doblin. A documentary showing the method applied on three people with PTSD is “Trip of Compassion”. One research article published in Lancet Psychiatry with treatment resistant patients in 2018 showed that more than 50% of participants did not meet PTSD criteria one month after the treatment : full pdf here.

Physical activity

Over the last year I spent some time learning and thinking about how our body moves. One problem is that our body did not evolve for our current environment. It seems that the most damaging habits that we have are: sitting for extended periods of time and wearing shoes with thick soles. The part about sitting is probably obvious for many people. The shoe situation is less obvious because it happened more recently. The biomechanics of walking and running in shoes with thick soles are very different than barefoot walking/running. The book “Born to run” got me into minimalist shoes more than 10 years go and I never looked back. More recently researchers like Daniel Lieberman and Irene Davis did experiments to show what was already quite obvious, barefoot running has less impact on the body than running in shoes with thick soles.

Another thing to consider is the overall biomechanics of the whole body. Many of us have imbalances between various muscle groups. Therefore we do not move in the best way possible and become prone to injuries. One approach that evaluates the whole body is called functional movement and it is promoted by Gray Cook. You can watch a good presentation he gave at Google. In Gray Cook’s opinion we need a systematic approach: first have a basic level of health, then evaluate and improve functional movement, and only after that move to fitness (amateur level athlete) and maybe even skills (professional level athlete). If we jump directly to fitness and skills we have a higher risk of creating even more imbalances in the body resulting in injury.

In my clinical practice I see patients with chronic pain after various injuries. I think one important question to ask is why they were injured in the first place. For example why would somebody get a herniated disk? Or knee osteoarthritis? I think most injuries are a result of the imbalance between tissue quality and load. Major factors that impact tissue quality are prediabetes/diabetes and obesity (through the metabolic consequences). Major factors that impact load are obesity and poor biomechanics. We need to address al these factors in everybody. Ideally we should strive to prevent injury. For example, a physical therapist or another trained professional should do annual well being evaluations in everybody and see what things can be improved to prevent injury.

In my own case I changed my diet to improve my health, I started to incorporate yoga to improve my functional movement and I am looking into better running techniques to improve my fitness.

Good resources:
- many talks by Daniel Lieberman and Irene Davis on youtube
- for running advice and training I like Mark Cucuzzella. Just watch how he runs barefoot in this video
- for whole body exercise a decent resource is Diamond Dallas Page Yoga

Diabetes

This is just a general overview. Everybody should discuss with their medical provider before making any changes in their life style.

Diabetes is a massive healthcare issue. In the United States about 1 in 10 people are diabetic. This is an increase from 1 in 100 people who were diabetics in the 1950s. What changed from the 1950s is the food. Diabetes affects everything in the body from bones, muscles to heart and kidneys. Most doctors focus on one or a few organs when talking with patients about diabetes, but truly all organs are affected.

Sadly, the medical system does not do enough to help the diabetic patients. Normally, the fasting blood glucose is around 80-90 mg/dl, but in diabetic patients we came to consider acceptable values that are at least 1.5 to 2 times higher. Imagine going to the doctor with your blood pressure twice as high as normal. Everybody will freak out. So why do we tolerate these high blood sugar values? I think there are two issues. Most doctors have no clue about the true damage caused by diabetes and the second issue is that most doctors do not know how to really manage diabetes and achieve normal blood sugars.

Nowadays the most common diabetes is diabetes type 2 which is more than 90% of all diabetes cases. The most common pathway to diabetes type 2 is weight gain. When we eat carbohydrates and proteins our body secretes insulin and insulin helps to store some of the energy as fat. Over time our fat stores become full. The body develops insulin resistance because there is no more place to put all the excess energy. The insulin levels keep increasing to compensate for the insulin resistance. High insulin level by itself is actually detrimental to health (see this paper by DeFronzo). In the end, the organ secreting insulin (pancreas) may get exhausted by years of over secreting insulin and stops making insulin.

So how do we fix diabetes? There are two issues in diabetes type 2: insulin resistance and high blood glucose. To decrease the insulin resistance the obese patients need to lose weight. As long the insulin levels are high it is very hard to lose weight because insulin is a growth hormone. Therefore, the best way to lose weight is to decrease the insulin levels which can be achieved with low carbohydrate diet or fasting or a combination of fasting and low carbohydrate diet. For normalizing blood glucose levels the best is to follow a low carbohydrate diet.

Low carbohydrate diet is not that hard to achieve. Most people like the foods included in this diet: meat, dairy, eggs, leafy vegetables. One doctor who has diabetes type 1 is Dr. Richard Bernstein. He was diagnosed with diabetes type 1 in 1946 at age 12. He has been practicing low carbohydrate diet since the 1970s. Dr Richard Bernstein has an amazing practical and theoretical knowledge in the diabetes field. He is sharing his knowledge on youtube (recommend Dr. Bernstein's Diabetes University) and in his book The Complete Guide to Achieving Normal Blood Sugars. Other resources include: the diet doctor and low carb md podcast. Virta Health published a bunch of papers about low carb diet: https://www.virtahealth.com/research.

Fasting is an even more accepted practice. Most religions have a form of fasting and fasting has been practiced for thousands of years. One of easier form of fasting is time restricted fasting or intermittent fasting, An easy way to start is 16 hours of fasting and 8 hours of food every day. Multiple days of fasting are also possible. It is important to keep in mind that are our bodies are very efficient and for every full day of fasting we might lose as little as half a pound. Jason Fung is one of more recent advocates of fasting with multiple books and videos on the internet. Fasting is not good just for diabetes, but also for health in general. This a good review article from the New England Journal of Medicine about the benefits of fasting: de Cabo and Mattson. NEJM 2019.

Learning

Over the last year a few books/podcasts had a big influence on me:
- the book “Dr. Bernstein's Diabetes Solution” describes a very comprehensive approach for diabetes treatment. I recommend this book to all my diabetic patients, I actually bought a copy to lend to my patients.
- Rhonda Patrick podcast with Ronald Krauss changed the way I view LDL cholesterol.
- Peter Attia podcast with Rick Johnson changed the way I view sugar and fructose. I rarely eat products with added sugar nowadays.

Chronic pain

Approximately 100 million people live with chronic pain in US and for half of them pain is really impacting their life. The mechanisms of chronic pain are much more complicated than most people realize. This is just a general diagram of the pain network. Everybody has a personal pain experience because of the individual variations at so many levels.

Currently, our medical system is focused on medications and procedures. The success is not that great since these treatments do not address the underlying problems. I think a better way is to address the whole person and try to calm down these vicious cycles started by acute pain (increased muscle tone, hyper-reactivity of the autonomic nervous system/endocrine system, increased inflammation) and change the processing of information in the central nervous system (spinal cord and brain). For each potential pain treatment we should look at how it influences the following four final goals:
- decrease sensitization in the central nervous system
- decrease inflammation in the periphery and central nervous system
- improve self healing/homeostasis
- improve muscle activity and decrease joint load
Current medications and procedures almost do not accomplish any of these goals. What actually works is the good old wellness measures. The four areas essential for our well being are: nutrition (fasting seems to be a very potent treatment), physical exercise, sleep (really undervalued today) and mental health/spirituality. Just think about fasting and sleep. Both are free resources and both work on all the four goals above. If you are suffering from chronic pain and consider fasting please discuss this with your medical provider since it can affect other medical conditions.

Animal pain research

Over the last 15 years I have been involved in the pain field initially in research and then in clinical practice. I regularly attend scientific meetings. It continues to amaze me the amount of pain research done on mice/rats. Honestly, I do not think the findings in mice/rats are transferable to complex conditions like human pain. For a very simplistic and partial view please see my section about pain mechanisms. The result of so many billions of dollars spent on animal pain research is very lacking. Not much in terms of treatments came out of this research.

At recent scientific meetings the hype was about how male mice and female mice are different. Some researchers seem to believe that because most research was done on male mice, the results were not suitable for translational (treatment finding) research. Following this reasoning I am baffled that they do not realize that the difference between female mice and male mice is much much smaller than the difference between humans and mice. Humans are very different creatures. Recently I saw an article in the journal Nature describing the significant differences between the brain neurons in humans and mice: Hodge RD et al. Nature. 2019 Sep;573(7772):61-68. One of the conclusions of this paper is: “Notably, serotonin receptors are the second-most-divergent gene family, challenging the use of mouse models for many neuropsychiatric disorders that involve serotonin signalling.” Pain circuits are intimately connected to the the brain areas involved in various psychiatric diseases (e.g. anxiety, depression). Earlier this year one article that was very hyped on the internet talked about the areas of amygdala in mouse that seem to be important for the “unpleasantness of pain”: Corder G et al. Science. 2019 Jan 18;363(6424):276-281. I find it hard to believe that the findings of the Corder G et al. paper will have any importance for the human pain.

I think we should focus on animal research only to understand the fundamental mechanisms of biology (e.g cell biology, molecular biology) and use human research to understand complex diseases like pain. Even the fundamental mechanisms at the cellular level do not always translate from mice to humans. There are a few studies looking at functional knockouts in humans that were not predicted from studies in mice: Saleheen D et al. Nature. 2017 Apr 12; 544(7649): 235–239 and Narasimhan VM et al. Science. 2016 Apr 22; 352(6284): 474–477.

How to improve your sleep

One of the popular beliefs is that you have enough time to sleep when you are dead. I have to admit that until recently I did not pay attention to my sleep. But over the last year I taught a wellness class for my resident physicians and sleep is an essential part of a healthy living. I felt I had to read more about sleep. One book that I really enjoyed was: “Why We Sleep: Unlocking the Power of Sleep and Dreams” by Matthew Walker.

Matthew Walker makes a great case for sleep. Sleep is pretty much the Swiss army knife for health and it is free. Poor sleep has been correlated in studies with all the diseases you can imagine from heart disease, obesity, diabetes, degenerative brain diseases (Alzheimer’s) to cancer. The obesity connection is really interesting. Humans are the only animal who voluntarily deprives itself of sleep. The other animals decrease sleep only when they don’t have enough food. This connection sleep/food is likely preserved in us. When we don’t get enough sleep our brains/bodies are guessing that we are food deprived and we feel like eating a lot of food high in calories (junk food).

Basically the recommendations I found so far are:
- Allocate enough time for sleep - at least 8 hours per night
- Use dim lights in the evening (or red lights if you have them), no screen time, turn your devices to night mode (reddish color of the screen)
- Cold room: 65-68 degrees F (use socks if needed, obviously this temperature is much easier to achieve in the winter)
- Decrease worry/anxiety: best is meditation, another option is to do journaling one hour before bed and end the journaling with a couple of things for which you are grateful that day
- No food/exercise for 2-3 hours before bed
- No alcohol in the afternoon/evening
- Limit/give up coffee (including decaf) or caffeinated beverage (i.e tea, Coke, Pepsi). If you sleep enough you might not need any of these
- Create the connection between bed and sleep, go to bed only when sleepy, don’t do anything else in bed (like reading or watching TV). If you don’t fall asleep get up and do something else
- Avoid sleeping pills, they do not induce normal sleep

And even more recommendations:
- If you snore discuss with your doctor about a sleep study, maybe you have sleep apnea
- If your sleep partner interferes with your sleep, consider sleeping in different beds/rooms

Matthew Walker appeared on a few podcast shows that I follow. You can listen to him on Peter Attia podcast: episode 1, episode 2 and episode 3.

Antibodies as treatment for pain

A while back I did a PhD in neuroscience. My work was focused mostly on the molecular mechanisms of nociception in the peripheral nervous system. At that time it was not clear which receptors would be a good clinical target for pain treatments. In the meantime it looks like the pharmaceutical companies had good results with two targets: CGRP (calcitonin gene-related peptide) for the treatment of migraines and NGF (nerve growth factor) for the treatment of pain due to osteoarthritis.

The CGRP antibodies and the CGRP receptor antibodies are on the market already (an overview here). One of the CGRP receptor antibodies is erenumab. The clinical studies are really good. In the STRIVE trial “a 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo)” . You can read The New England Journal of Medicine article on STRIVE trial here. But also there are concerns about safety: see articles here and here. It is really interesting how we got to CGRP as a target for the treatment of migraines (see this article). The mechanism of migraines is not clearly understood, but it seems that one cause is a seizure like activity called cortical spreading depression (CSD) that starts in the occipital lobe. The CSD triggers the clinical migraines by irritating the trigeminovascular system. Initially, substance P was thought to be important in causing migraines, but targeting substance P failed. Then, the attention moved to CGRP because it was found to be elevated in the blood during severe migraine attacks.

The NGF antibodies for the treatment of pain due to osteoarthritis are still under study in clinical trials. One NGF antibody is tanezumab. Concerns about safety abound: articles here and here. As the name nerve growth factor suggests, NGF is important for neuronal survival but also for the pancreas and the immune system. Maybe it will be a matter of finding a dose that has benefit and minimal side effects.