Hip
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The vagus nerve is not the only route.
Yes, there are four known routes through which inflammatory cytokines deriving from an infection in the body can trigger sickness behavior in the brain. If you wanted to stop all sickness behavior during an infection, I think you would have to block all four pathways.
One thing I can say for sure though is that it is not at all like experiencing PEM.
What would you say were the differences between your PEM symptoms and sickness behavior symptoms, and what if any were the similarities? This question is also for anyone else interested in answering it.
Just to help you, here is a list of symptoms that appear in sickness behavior:
Sickness behavior symptoms:
Fever
Malaise (the feeling you get when you come down with an infection like the flu)
Loss of appetite
Lethargy
Fatigue
Sleepiness
Decreased locomotor activity (general movement from place to place)
Altered sleep-wake patterns (circadian rhythm disruptions)
Cognitive impairment (brain fog)
Impairment of learning and memory
Low mood / depression
Loss of libido
Anhedonia
Anxiety
Irritability
Decreased social interaction
Increased hyperalgesia (more aches and pains)
Reduction in grooming (less keen on performing the normal daily ablutions)
Here is the CCC definition of PEM:
Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period usually 24 hours or longer.
at this point I can say that fatigue and lethargy are a result of poor energy production and a depletion of energy in every major bodily system.
You can of course speculate that poor energy production may be the cause of your fatigue and lethargy, and some researchers have indeed done this, hypothesizing that ME/CFS may be due to mitochondrial problems; but nobody knows for sure what is going on in ME/CFS. There are only theories at this stage.
One thing to be aware of, though, is that even in healthy people, the muscle fatigue they feel in their mind when they have significantly used their muscles is in part a psychological fatigue, and in part a real depletion of energy in the muscles.
I only recently became aware of this, but in there are in fact two mechanisms which lead to fatigue during normal muscle use: central fatigue and peripheral fatigue. I am talking about healthy people here.
Central fatigue is the psychological feeling of fatigue generated in the brain, and contrasts to peripheral fatigue, which is defined as the physical running out of energy in the muscles, or the running out of other factors needed to make the muscles work. For a fuller description of the two types of fatigue, see here: Muscle weakness - Wikipedia
One study I read on this subject discovered that when you use your muscles a lot, you get a serotonin build-up around the motor neurons in your brain (the motor neurons that are activating your muscles). The more you use the muscles, the more this serotonin engulfs your motor neurons. This flood of serotonin then creates a psychological feeling of muscle fatigue. This is central fatigue.
This central fatigue is not a real loss of physical muscle energy, but a feeling created in your brain that the muscles are tired. The idea of deliberately creating this psychological feeling of muscle fatigue is presumably to protect you from overusing your muscles, which could lead to muscle damage.
So you see that even in healthy people, a deliberately created psychological feeling of muscle fatigue is used to make sure you don't overwork yourself. Just as in sickness behavior, a deliberately created feeling of overall fatigue is created so that you conserve energy.
I mention this just to show that it is not so straightforward to work out whether the feeling of fatigue you have comes from a physical depletion of energy, or a feeling of psychological fatigue imposed on you by your own brain.
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