Dr. Martina Melzer, published: 03.06.2022

 

Deutsche Version

 

A malfunctioning autonomic nervous system, ANS for short, is from my point of view the epicenter, the core that lies behind syndromes like ME/CFS, POTS, fibromyalgia, long covid, irritable bowel syndrome, etc.. The second part of the epicenter is the limbic system - more on this in the "Mindset" strategy. These findings are not mine, but from all my research, courses, programs, books.

The first person who turned me on to the ANS was Australian Dan Neuffer. He wrote the book CFS Unravelled and founded the ANS Rewire program. He is a physicist and must have spent what felt like 10,000 hours doing intensive research. He talked to scientists and then made his own conclusions. I now even go so far as to claim: a malfunctioning autonomic nervous system plays a completely underestimated role in  many chronic diseases - from diabetes, to high blood pressure, to cancer.

What are the functions of the autonomic nervous system?

Here I have to elaborate, because: important.

The autonomic nervous system essentially consists of two major nerve cords: the sympathetic and parasympathetic nervous systems, both of which operate automatically and autonomously. The sympathetic nervous system is the activating part, and the parasympathetic nervous system, also called the vagus nerve, is the calming part. Together they control, regulate and influence the functions of the internal organs and other body systems: Eyes, lungs, thyroid, heart, stomach, intestines, liver, spleen, pancreas, kidneys, bladder, sexual organs, adipose tissue, hair roots, blood vessels, sweat glands, immune system, hormonal system. And besides, areas in the brain that perform vital functions: Cardiovascular regulatory center, respiratory center, swallowing, sucking, coughing and sneezing center, digestion, vomiting center, tear formation, pupil size, urinary bladder emptying. So the ANS is really a BIG PLAYER in us.

While the sympathetic nerve originates in the spinal cord, the vagus nerve runs into the brain stem. The nerve messenger acetylcholine serves to transmit signals in both nerve cords. In the sympathetic nervous system, there is also adrenaline and noradrenaline. The precursor messenger of norepinephrine is dopamine. Norepinephrine and epinephrine bind to so-called alpha or beta receptors located on the organs. Acetylcholine binds to so-called muscarinic receptors. By inhibiting or activating these binding sites, the neurotransmitters control the target organs.

Superior to the autonomic nervous system is the hypothalamus, a central control center in the brain that is connected to virtually all brain regions and the central nervous system. The hypothalamus receives signals from the limbic system (our emotion center) and other brain areas and sends signals to the pituitary gland, parts of the brain stem and the spinal cord. The main task of the hypothalamus is: to keep the organism in balance, to keep it healthy. For this purpose it controls the hormonal system, water balance, body temperature, food intake, cardiovascular system, activation or inhibition of the sympathetic or parasympathetic nervous system, sexual function, etc.

Autonomic nervous system and immune system

When immune cells or other components of the immune system detect a pathogen or other foreign substance that it considers potentially dangerous, it triggers an acute inflammatory response. This information is immediately sent to the brain. This happens primarily via the vagus nerve, whose numerous secondary branches all over the periphery "feel" what's going on. Eighty percent of the information relayed by the vagus goes from the periphery to the brainstem. But the sympathetic nervous system also picks up the "inflammation" information. Now the hypothalamus is activated and through it the nerve branches of the sympathetic and parasympathetic nervous systems that flow into the periphery.

Both are significantly involved in controlling and regulating the acute inflammatory reaction: The sympathetic nervous system communicates with all immune cells and organs primarily via the messenger substance norepinephrine, since they possess receptors for norepinephrine. If a pathogen, toxin or injury causes acute inflammation in the body, the sympathetic nervous system stimulates the immune system initally, which increases the inflammation. At the same time, the sympathetic nervous system tunes the entire body and organ functions to adapt to the acute event - for example, providing energy and shutting down tasks that are not so important at the moment. Via the so-called HPA axis (more in the strategy "Hormones"), more noradrenaline and adrenaline are released from the adrenal glands. Somewhat delayed then also cortisol.

As already mentioned, the parasympathetic nervous system initially sends pro-inflammatory signals to the hypothalamus. This probably also triggers the feeling of sickness, the so-called sickness behavior, with fatigue, fever, pain, bad mood. However, the descending nerve cords of the vagus nerve send an anti-inflammatory message. Receptors for the neurotransmitter acetylcholine are also found on all immune cells and organs. Thus, under normal circumstances, the vagus nerve ensures that inflammation subsides once the pathogen, toxin, or injury is removed. In this way, the nervous system, immune system and body return to balance - to their homeostasis.

The extent to which the hypothalamus activates the ANS, influencing inflammation and immune response, depends on the time of day, emotional state and current stress level, among other factors. This truly complex interplay is summarized under the unwieldy term "psycho-neuro-endocrino-immunology."

Connect, fight, flee, fawn or freeze?

Why does the ANS control and regulate so many important bodily functions? What is its overriding purpose? It serves to protect us, to ensure our survival. The autonomic nervous system constantly checks whether we are safe or in danger. If it senses danger, it prepares us to fight for our lives (fight-response) or to run (flight-response) in an emergency. If the situation seems hopeless and fight or flight is futile, it puts us into freeze-response. We play dead. Sometimes playing dead can also help the attacker pass by and not scent us. Another survival mechanism is submission (fawn-response).

These are all biological processes that can also be observed in wild animals. Example: A wolf in a pack fawns to the alpha animal because it cannot make prey alone. A lizard freezes because you touch it. It plays dead and thus says: Don't eat me. A gazelle races through the savannah at what feels like 100 kilometers per hour to escape the lion. A female polar bear fights with a male polar bear to save the life of her polar bear cub.

On the other hand, if our ANS gets enough signals that we are safe, we relax (rest) and can attend to the digestion of the last meal (digest). We also laugh, flirt, play, talk with other people (connection) and our pets. We are socially engaged (social engagement system).

The Polyvagal Theory

Dr. Stephen Porges has put forward the so-called polyvagal theory. He hypothesizes that two parts of the vagus nerve have evolved over the course of evolution. The older part is the dorsal vagus nerve, which extends into the abdominal organs and occurs in two states of tension (high tone, low tone). In low tone it takes care of rest, relaxation, digestion, sleep. In the high tone it causes the freeze reaction, puts the body into survival mode and shuts down all non-essential body functions. The evolutionarily younger part of the vagus nerve is the ventral vagus nerve, which only extends to the heart and is primarily important for safety and connection.

How does the ANS get out of balance?

If we are in a real or perceived dangerous situation, the sympathetic nervous system is activated. The heart races, we sweat, are tense, alert, the stomach grumbles. We are ready for fight or flight. If the situation feels hopeless, the dorsal vagus goes into overdrive. We are frozen, stiff, the heart beats slowly, the limbs are poorly supplied with blood. Once the dangerous situation is over, we calm down, relax, breathe deeply, are relieved, ready to connect with others. The ventral vagus is ramped up, the sympathetic nervous system and dorsal vagus go into a calmer mode. This is how it ideally proceeds when the autonomic nervous system is in balance and able to regulate itself.

However, chronic stress and trauma can throw the ANS out of balance. Stressors and trauma can be physical as well as psychological and/or environmental.

Physical factors include: heavy exercise, accident, injury, surgery, unhealthy diet, lack of exercise, illness, infections, vaccinations, childbirth.

Mental factors include: Bosses, stressful job, school, college, job loss, divorce, relationship problems, physical/sexual/emotional abuse in childhood or adulthood, financial problems, information and news overload, marriage, caring for a relative, constant availability, lack of time, too many demands, personality traits.

Environmental factors include: Molds, chemicals, air pollution, contaminated drinking water, pesticides.

From my perspective, the difference between chronic stress and trauma is that trauma is simply at a higher intensity level than "just" chronic stress. People often think of trauma primarily in terms of a catastrophic event such as a bad accident, sexual abuse, war, or a hurricane. Much more often, but often overlooked, developmental trauma occurs when children experience trauma over a long period of time, usually at the hands of their parents or other close relatives, but also at the hands of teachers and classmates.

I think that not only the autonomic nervous system gets out of balance due to such factors, but also the limbic system. Why? Sensory perceptions from the outside world and the inside world are sent via the vagus nerve (and other pathways) to the hypothalamus. The hypothalamus sends the information to the limbic system for evaluation. It decides whether the sensory perceptions mean safety or danger and in turn sends the appropriate results to the higher, newer part of the brain, our thinking brain. And of course to the hypothalamus, the control center of our autonomic nervous system. Depending on whether the outcome of the limbic system is danger or safety, the hypothalamus adjusts the sympathetic and parasympathetic nervous systems accordingly. If the limbic system is now misdirected due to the above-mentioned factors, it preferentially sends on danger signals, thereby upsetting not only our bodily functions, but also our world of thought and our behavior.

In most cases, no single factor is sufficient to cause lasting disruption of the autonomic nervous system. Several of the above-mentioned examples must come together. Then there are various possibilities of misregulation: the sympathetic nervous system simply remains permanently active in the unhealthy survival mode and the parasympathetic nervous system cannot jump into its healthy mode. Or unhealthy sympathetic nervous system and unhealthily activated dorsal vagus are switched on at the same time. Some refer to this as "functional freeze." Or the healthy mode of the sympathetic nervous system cannot ramp up. In all variants, the ventral vagus is also dysfunctional, we are not in flow but stuck in survival mode. Medically, the dysfunctions are called dysautonomias.

Do some stressors sound familiar? Play detective again. Sit down, take a piece of paper, your journal or smartphone and do some soul-searching. What stressors might be playing a role in your life? Did several come together before the onset of your illness? This sleuthing is absolutely essential to your recovery!

Here are two very good videos that explain the ANS and how it gets out of balance due to stress and trauma:

Sources: Polyvagal Institute, Irene Lyon

Is a misdirected ANS the cause of many syndromes and diseases?

According to my personal view and research: Yes. Overactivity of the sympathetic nervous system, from a conventional medical point of view, can manifest itself with these symptoms, for example: Trembling, goose bumps, pain of all kinds, palpitations, cardiac arrhythmias, sweating and freezing at the same time, flatulence, constipation or diarrhea, fluctuations in blood sugar, high blood pressure. A throttled activity of the sympathetic nervous system is accompanied by: Circulatory problems when changing position (orthostatic intolerance), fatigue, exercise intolerance, intolerance to heat, dizziness, low blood pressure. Overactivity of the vagus nerve can cause such symptoms as: Diarrhea, copious saliva, slowed heartbeat. Decreased activity of parasympathetic nerve can make dilated pupils, sicca syndrome, dry mouth, palpitations.

From the polyvagal perspective, depending on the ANS status, the following picture emerges: If the sympathetic nervous system is too active it is associated with anxiety, anger, restlessness, increased alertness, rapid heartbeat, shallow breathing, concentration problems and inability to switch off. If the dorsal vagus is in too high a state of tension this leads to stiffness, a numb feeling in the body, dissociation, hopelessness, brainfog, fatigue, lack of energy, thinking problems. In chronic stress or trauma, these two states alternate as in a ping-pong game - a boom and bust cycle (too much activity - crash) with sympathetic high, sympathetic low, parasympathetic high and parasympathetic low occurs. Or they are both turned on at the same time.

All in all, a maladjusted ANS can cause myriads of different symptoms. Because there are so many variations of how it can be misdirected, the symptoms are also so varied.

It is scientifically accepted that POTS, or Postural Tachycardia Syndrome, is dysautonomia. Many studies also mention ANS dysfunction as an important disease mechanism in ME/CFS and Long Covid. In MCAS, mast cell activation syndrome, and Ehlers-Dahnlos syndrome, dysautonomia plays a major role. Irritable bowel syndrome is considered to be a disorder of the gut-brain axis - that is, the faulty interaction of the gut nervous system, sympathetic nervous system, and parasympathetic nervous system. Dysfunction of the ANS is suspected in fibromyalgia, and likewise in depression, anxiety disorders, and (complex) post-traumatic stress disorder (PTSD). There is evidence that dysfunction is a contributing cause in autoimmune diseases, cancer, hypertension, cardiovascular disease, diabetes, obesity, and other typical diseases of civilization. Depending on genetic predisposition, lifestyle, environmental and stress factors, you get disease A or B.

 

Read blog-article: Is Long Covid = ME/CFS?

What is the Cell Danger Response (CDR)?

In connection with the dysfunctional nervous system that is stuck in its survival mode, I must briefly mention what is called the Cell Danger Response (CDR). CDR, according to its discoverer Dr. Robert Naviaux, is an evolutionary mechanism that provides healing and recovery in the body at the cellular level after injuries and (life-threatening) dangerous situations. These situations include infections, psychological or physical trauma, lack of oxygen, stress, environmental toxins, accidents, among others.

These factors trigger a stress response in the body and this activates the CDR. It causes the cells to go into a hypometabolic state, so their metabolism is shut down, you go into a kind of hibernation. The central site of action is the mitochondria, the little energy power plants in our cells. Immune system, autonomic nervous system, metabolism, hormonal system, gut microbiome, gut nervous system, genes, sleep, behavior and thinking all adjust to this status. Naviaux lists some "symptoms" that accompany it: Social withdrawal; interrupted sleep; abdominal, head and muscle pain; sensitivity to light, sound, smell and touch; flu-like symptoms. CDR goes through various stages until the body is healed and fully functional again. Then the energy is back, too.

Naviaux suspects that in many chronic diseases, including ME/CFS, this healing cycle is incomplete and the body is stuck in survival mode. He says that the perception of danger and safety can be traced to and affects every cell and mitochondrion.

I think CDR is the molecular explanation for all the negative effects caused by an autonomic nervous system misdirected by stress. After all, the activation of fight, flight, fawn or freeze is for survival in a dangerous situation. If the organism is stuck in survival mode, it cannot heal and become healthy.

How do you bring the nervous system back into balance?

From my point of view, it is essentially a matter of making the limbic system and the autonomic nervous system understand that you are safe 95 percent of the time (if this is not the case for you, for example because of domestic violence, you urgently need to make yourself safe!) The point is to extend the window of tolerance beyond which both systems classify an internal or external stimulus as a danger. You have to manage to get the organism out of survival mode and into healing mode. Sympathetic and parasympathetic systems allow us to be physically and mentally active, to be social, to rest, to recharge our batteries, to digest food, to sleep restfully - when they are in balance. I always say: it's all about balance!

How do you stop survival mode? Through neuroplasticity (= brain training = the brain is malleable and changeable). Roughly speaking, the limbic system and ANS perceive so many stimuli as danger over time that the associated neural pathways and connections become stronger and stronger. One classifies more and more things as danger, avoids more and more, renounces more and more. The brain also classifies movement and bodily sensations as a source of danger - even if they have no serious causes, but are simply triggered by the malfunctioning of the ANS (of course, always have new symptoms checked!). It is now a matter of turning the previous data highways (danger mode) in the brain into side roads and creating new highways (safety mode), which are now only small side roads. Through neuroplasticity we can learn new behaviors and discard old ones, adopt healthier conversations with ourselves, change our lifestyles, not evaluate things but simply notice them first. We can learn to deal with stress factors differently, to perceive symptoms only as bodily sensations for the time being. All this requires a lot of strength, self-confidence, persistence and time.

From my point of view, with regard to syndromes such as ME/CFS, fibromyalgia, POTS and irritable bowel syndrome, but also with regard to (complex) PTSD, depression and anxiety disorders, we have to take a two-pronged approach to reshape the brain and regulate limbic systems such as ANS: a top-down approach and a bottom-up approach.

By a top-down approach, I mean influencing limbic system and autonomic nervous system in the older part of the brain, the brainstem, via the evolutionary younger part of the brain - our thinking brain, the cortex. With it, we consciously think and plan and actively control our behavior. We can influence the way we talk about ourselves. We can tell ourselves "I am safe." We can meditate and practice mindfulness, simply notice our symptoms and emotions, calm our mind. We can visualize beautiful things from the past or imagine beautiful things in the future. We can create an imaginary place where we are 100 percent safe and where we can always go in our mind. Cognitive behavioral therapy is also a top-down approach.

A bottom-up approach, as I understand it, comes from the body, through purposefully influencing our breathing, muscle tension, posture. And ideally without constantly drifting away mentally. All these things are perceived by the vagus nerve and sent to the hypothalamus and the limbic system. Calm, deep breathing, relaxed muscles, an upright posture signal safety. That's why techniques like yoga, progressive muscle relaxation, Feldenkrais, breathing exercises, vagus training, influencing heart rate variability and EFT tapping (Emotional Freedom Technique) are so useful. Because if the body is in survival mode, you can try as hard as you want to change your thinking and behavior, it won't work. It only works when your body feels safe - at least temporarily. You can say to yourself "I am safe", but as long as you remain totally tense, the sentence is of no use at all. If you say it, exhale deeply at the same time and relax your muscles, then the signal "safety" arrives not only in the younger but also in the older part of the brain.

One of my favorite exercises is orienting: Sit, stand, lie down, feel your body, the points of contact with the ground, notice what you see, hear, feel, taste, smell. What calms you down? What worries you? Are there more signals for safety? Then you are safe - in your body and your environment.

Most mind-body techniques are a combination of "top-down" and vice versa.

Emotions can also be influenced from above and below. More about this in the strategy "Mindset".

In addition to these techniques, it is essential for our sense of safety to connect with other people who make us feel good. Whether we talk to them, laugh with them, sing with them, play with them, do something with them, cry with them, throw up with them. Pets can also establish this sense of safety. And, when we connect with nature. Just a few minutes in nature is enough to regulate your nervous system. Even looking at nature pictures! That's why I created a little video about it with my own photos:

There are so many ways to retrain your brain! On the "Useful" page, I've linked to some programs that basically all have neuroplasticity at their core. You have to find for yourself the things that feel good to you, that you enjoy, and that you would do over a long period of time.

 

PS: Of course, I research and check everything I write here as well as possible. Nevertheless, I am only human and make mistakes. In addition, I may draw completely different conclusions as someone else would. Simply because they fit my story. But every story is different.

Important: The content on this page is for informational purposes only and is not a substitute for talking to your doctor or other therapist. The content reflects my personal experiences, research and findings that have helped me and that I therefore want to share. However, in your personal case, completely different things may play a role and other things may help. Please talk to your doctor or therapist before making any decisions that affect your physical or mental health. Also important: I don't want to convince anyone of anything here. Rather, I want to point out possible ways that hopefully can help some people to improve or overcome their Fatigue or ME/CFS.

 

sources

Thews, Mutschler, Vaupel: Anatomie, Physiologie, Pathophysiologie des Menschen

Eva Soto-Tinoco, Natalí N. Guerrero-Vargas, Ruud M. Buijs: Interaction between the hypothalamus and the immune system. Experimental Physiology 2016

Leal, Â., Carvalho, M., Rocha, I., & Mota-Filipe, H. (2018). Inflammation and Autonomic Function. In (Ed.), Autonomic Nervous System. IntechOpen

Content of Polyvagal-Akademie. Online: https://polyvagal-akademie.com/

Content of Irene Lyon. Online: https://irenelyon.com/

Content of Jessica Maguire. Online: https://www.jessicamaguire.com/

Dan Neuffer: CFS Unravelled

Alex Howard: Decode your fatigue

Prof. Georg Hasler: Die Darm-Hirn-Connection

The Dysautonomia Project. Online: https://thedysautonomiaproject.org/

Matthijs Kox,  Lucas T. van Eijk, Jelle Zwaag, ,Peter Pickers: Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. PNAS 201

Bucsek MJ, Giridharan T, MacDonald CR, Hylander BL, Repasky EA. An overview of the role of sympathetic regulation of immune responses in infectious disease and autoimmunity. Int J Hyperthermia. 2018

Naviaux R: Perspective: Cell danger response Biology—The new science that connects environmental health with mitochondria and the rising tide of chronic illness. Mitochondrion 2020

Naviaux R: Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response. Biology 2019

Taylor AG, Goehler LE, Galper DI, Innes KE, Bourguignon C. Top-down and bottom-up mechanisms in mind-body medicine: development of an integrative framework for psychophysiological research. Explore (NY). 2010