Ending, FINALLY, the shameful stigmatization of fibromyalgia and chronic fatigue syndrome: Part 1
This article series presents an innovative disease mechanism for fibromyalgia, chronic fatigue syndrome, and related disorders.
Short overview:
Part 1 explains the basic disease mechanism of fibromyalgia and related, so-called functional somatic syndromes (FSS), like tension headache or irritable bowel syndrome. CFS develops in a special way from this mechanism, and is explained in Part 3.
Part 2 explains how the FSS develop in two phases from the mechanism presented in part 1.
Part 3 explains the temporary symptoms of the FSS exemplarily with irritable bowel syndrome, premenstrual syndrome, electrohypersensitivity, and multiple chemical sensitivity. It explains also the very uncommon disease mechanism of CFS.
Fibromyalgia and chronic fatigue syndrome (FM/CFS) are severe, debilitating diseases.
Especially tragic for those affected is the frequent psychiatrization and stigmatization due to the lack of medical findings. Charges such as: “Come on, get a grip. It’s all in your head.” are the painful consequences.
This article wants to end this stigmatization by providing an innovative physiological disease mechanism that, finally, can plausibly and scientifically explain the symptoms of these and related disorders.
After reading the article, no one can claim that there is no medical explanation for the alleged “impossible” symptoms of FM/CFS.
To develop the disease mechanism, I printed and read about 800 original scientific articles, added thousands of comments, and finally used 300 of the articles. This disease mechanism is therefore not at all far-fetched, but thoroughly researched and well-founded.
But don’t worry, the article describes the disease mechanism conclusively with only 16 references (the complete hypothesis can be found on my homepage). Some paragraphs of Part 1 are a bit technical. Hang in there ... Part 2 and 3 are simple and like the clear view after the summit ascent. You will see and understand …
Brief information about me: I have a master’s degree in computer science and acquired profound knowledge in neuroscience over the course of my life.
Now let me get straight to the heart of the matter:
„Extinction neurons“ in the brain are a common point of attack for different types of stressors
In the brain, there exists a class of neurons, the so-called interneurons. Interneurons bear this name because they only form very short nerve connections to neighboring neurons. In contrast, other neuron types can form connections up to 1 m long.
A type of interneurons, named „PV+ interneurons“, has a special feature: their permanent high activity makes them extremely sensitive to various kinds of physiological stress.
The “Interneuron Energy Hypothesis” describes the reasons and implications of the high sensitivity of these interneurons. See the abstracts of PMID 26284893 (2) and 24896567 (3) (the PMID is the article number at www.pubmed.gov). Here, only the high sensitivity of this type of neurons is important.
A part of the PV+ interneurons are an important carrier of a certain type of memories, the so-called extinction memories. The neurons physically storing or carrying extinction memories are called extinction neurons.
The function of extinction memories is easy to understand. Probably you read about Pavlov’s dog, who was trained to salivate when a bell rang. Read here and here the story, if you don’t know it. It’s a must read.
To summarize, Pavlov’s dog was repeatedly presented with a ringing bell when his food was served. Afterwards he produced saliva even when no food was served, but only the bell rang.
This procedure is called classical conditioning and it creates a memory that represents the association between the food and the ringing bell. This memory is also called a conditioned reaction.
Some time later, the dog was repeatedly presented with the ringing bell without receiving food at the same time. As a result, the dog finally stopped salivating when the bell rang. This procedure of loosing the conditioned reaction is called extinction learning.
Countless experiments followed Pavlov’s discovery. They mainly used aversive (i.e. negative) stimuli to investigate associations between stimuli such as an electric shock and a neutral stimulus such as turning on a light.
In the classical experiment, which you have probably heard of, a rat is conditioned with a mild electric shock so that it freezes when an light is turned on.
If the light then lights up several times without simultaneous electric shock, this represents extinction learning, and the rat loses the freezing reaction.
The association between the aversive and the neutral stimulus that is created in classical conditioning is named aversive memory. The memory that forms during extinction learning is named extinction memory.
The most important result of the research on classical conditioning was that during extinction learning the aversive memory that was created in the process of conditioning is not erased, but rather blocked by the extinction memory which formed during the procedure of extinction learning.
The main function of extinction memories is therefore to block, or control, other memories.
Extinction memories and the various kinds of memories controlled by them have several crucial properties:
- Many memories, in particular aversive ones, are inseparably associated with physiological reactions. For example the memory Pavlov’s dog developed to the ringing bell and the simultaneously presented food is inseparably associated with increased saliva production.
- Most importantly, in order to block memories, extinction neurons constantly send inhibitory (blocking) signals to neurons that carry those memories. Neurons carrying such memories are so-called principal neurons (PNs). Extinction neurons need to send permanently inhibitory signals to principal neurons, because unfortunately nature constructed principal neurons in a way that they get immediately and continuously active, when not receiving inhibitory signals.
- Aversive memories memories develop during all kinds of negative experiences, including the many physically and emotionally painful experiences made during childhood, and are all bestowed with extinction memories. Time by itself is a kind of extinction procedure.
- Interestingly, aversive memories also include a type of brain-internal immune memories, which are crucial to understand the development of CFS, see below.
Already at this point of the discussion, it is obvious that a dysfunction of interneurons must induce horrible symptoms because it entails an automatic and voluntarily not controllable activation of old aversive memories and the associated physiological reactions.
Imagine, only those extinction neurons that control a single strong fear memory of your childhood stop functioning.
The fear memory and the associated physiological reactions would immediately get active, and you would immediately feel strong, unexplainable muscle cramps, elevated respiration, fear emotions, etc.
And these symptoms would not go away until the extinction neurons would restart to work.
That means, from the point of time on these extinction neurons ceased functioning, your normal life would just be over. You would need to stop working, and you would ceaselessly bother doctors with complains about your symptoms.
And of course those doctors would never find a cause of your condition, because a selective dysfunctioning of extinction neurons cannot be diagnosed with the currently available diagnostic tools.
So, at this point it is clear that dysfunctioning of extinction neurons is a theoretical disease mechanisms that could make you chronically sick, without any medical findings … as with the FSS.
I’m sure you understand what I’m getting at …
… exactly, dysfunctioning of extinction neurons could theoretically be an explanation for the FSS, like fibromyalgia and chronic fatigue syndrome.
But can it also be a real and scientifically provable explanation?
In order to answer this question we have to investigate the following points:
- Is there scientific proof that dysfunctioning of extinction neurons really cause symptoms?
- If yes, are these symptoms similar to those of the FSS, thus could explain the FSS, including fibromyalgia and CFS.
So far, we could only theoretically deduce that dysfunction of neurons inhibiting old memories should lead to overactivity of these memories and induce physical and mental symptoms in the affected person. And it seems hopeless to test the presumed effect, because how is it possible to deactivate among hundreds of millions of neurons in the brain exactly those which inhibit a certain fear memory?
But then a group of researchers around Julien Courtin and Cyril Herry from the University of Bordeaux in France succeeded in something incredible (1).
Using state-of-the-art optogenetic methods, they were able to experimentally deactivate exactly those extinction neurons in mice that were responsible for inhibiting a certain fear memory.
Imagine what this means. This is exactly the previously unthinkable experiment that is necessary to check whether a dysfunction of extinction neurons really causes symptoms.
And indeed, the result of this experiment met the theoretical expectations:
The mice in which the extinction neurons were deactivated developed a strong anxiety response in the form of a freezing reaction, although they were not exposed to any anxiety stimulus and were calm in their normal environment.
This research result clearly shows that the lack of activation of extinction neurons, for example triggered by infections, toxins, extreme or prolonged stress, can cause physical and mental symptoms.
And if one examines in detail which symptoms are triggered by dysfunction of extinction neurons, one does indeed find a strong overlap with the symptoms of FSS.
I describe the technical details of this argumentation, as well as the study by Julien Courtin and Cyril Herry (1) in a separate article. It is very interesting, but somewhat technical. You can skip it for now and read on here.
Now that it has been clarified that dysfunction of extinction neurons can indeed produce the symptoms of the FSS, the final question is how such dysfunction can develop to cause a specific FSS in an individual.
Read in Part 2 how such a dysfunction can develop in two phases.
Convenient link to: Part 3
References
- Courtin, J., Chaudun, F., Rozeske, R. R., Karalis, N., Gonzalez-Campo, C., Wurtz, H., … Herry, C. (2013). Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression. Nature, 505(7481), 92–96. doi: 10.1038/nature12755
- Kann, O. (2016). The interneuron energy hypothesis: Implications for brain disease. Neurobiology of Disease, 90, 75–85. doi: 10.1016/j.nbd.2015.08.005
- Kann, O., Papageorgiou, I. E., & Draguhn, A. (2014). Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks. Journal of Cerebral Blood Flow & Metabolism, 34(8), 1270–1282. doi: 10.1038/jcbfm.2014.10
- Optogenetics. (2019, August 8). Retrieved from https://en.wikipedia.org/wiki/Optogenetics






