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The Study

The study, “Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load“, used a non-invasive technique called surface electromyography to assess the electrical activity (muscle fiber conduction velocity) as small amounts of force were applied to the biceps muscle.  If I have it right muscle fiber conduction velocity refers to the speed with which electrical activity results when force is applied to the muscle fiber. People with ME/CFS or fibromyalgia and healthy controls were included.

The authors reported that the pain in both ME/CFS and FM “particularly involves the muscles”. That was music to my ears as exertion typically produces muscle burning sensations and feelings of tight, contracted muscles that are impossible to ignore.

Fibromyalgia

“Negligible” levels of force were all that was required to produce a dramatic uptick in muscle membrane activity in FM.

A great deal of evidence suggests that something in the muscles in off in FM. The 2019 FM study “Fibromyalgia: Increased reactivity of the muscle membrane and a role of central regulation” produced a finding that seemed to astonish the researchers. They found that the largest increase in muscle membrane activity occurred when a “near negligible force” was applied to them.

That seemed to imply that the muscles were in a state of near activation, and just needed the slightest push to prod them into action.

That could be the result of two things: the muscle cells were being activated more quickly, or the membranes around the muscle cells were in a constant state of excitation. Since there was no evidence of increased muscle recruitment, the authors concluded that overly excited muscle membranes were the key.

Despite the fact that the muscle membranes were apparently itching to jump into action, the authors found no evidence of increased muscle activity overall. That suggested that the motor neurons in the central nervous system were feeding the muscles a steady stream of signals that was leaving them on high alert – but not quite pushing them into action.

Muscle studies are rarer in chronic fatigue syndrome (ME/CFS), but while the disease is more known for fatigue, muscle pain is common. This study’s unique feature was that it assessed muscle membrane functioning in both ME/CFS and FM. I’m fairly sure that nothing like this has been done before.

Results

The membranes surrounding the muscle cells were more excitable in both ME/CFS and FM patients compared to the healthy controls, but there the similarities ended.

As in prior studies, the muscle fiber conduction velocity (MCFV) rose abnormally high when the slightest forces were imposed on the muscles of FM patients.

The muscle conduction velocity rose “sharply” in ME/CFS as well – but only when higher levels of force were applied. . The authors noted that these levels were “far above” those of the healthy controls. The people with ME/CFS, then, didn’t exhibit the excitable response at very low levels of force that the FM patients did. Their muscles were more excitable than the healthy controls but only when a particular level of force was reached.

Different kinds of motor neurons are associated with different kinds of muscle cells. During exercise, the slow motor units linked to aerobic muscle fibers are activated first and then the motor units regulating anaerobic muscle fibers are activated next. The authors proposed that the hyperactivated motor neurons in ME/CFS were associated with the activation of thicker, more anaerobic muscle fibers.

Then they pointed a finger at the early entry into anaerobic energy production that various exercise studies have found in ME/CFS: the people with ME/CFS were  quickly blasting through their aerobic capacities and running into an anaerobic wall.

Next came a key question: could the amplified motor conduction times seen in ME/CFS have been due to muscle disuse or deconditioning? The answer to that couldn’t have been clearer. Deconditioning would have produced the opposite result – reduced muscle fiber conduction, not the increased muscle fiber conduction they found.

Similar Symptoms – Different Causes?

Fibromyalgia

The studies from this Dutch group suggest that FM and ME/CFS are both similar and different. Dramatically increased levels of muscle activation are seen in both.

In fibromyalgia, abnormally high muscle conduction velocities occur at very low force levels. This appears to result from a constant stream of signals from the central nervous system that’s leaving the muscle membranes in a constant state of near activation.

The authors suggested that a process similar to central sensitization was underway in FM patients’ muscles. Either the muscles were being fed too many signals to activate or the inhibition system designed to keep them in check was not working.  Either way, the central nervous system was throwing the muscle activation system out of whack.

Evidence of a kind of hyper-excited muscles in FM goes way back. A 1989 study, “Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia”, found that the muscles in FM tend to stay in an activated state long after a task has finished. It also found evidence of twitchy muscles which failed to relax or calm down between contractions.

Mental exertion was all it took to activate the trapezius muscle in FM in one study.

Other studies suggest problems with inflammation, reduced energy production, reduced blood flows and high levels of oxidative stress may be present in FM

patients’ muscles.

It’s surprising, given how rich the research on muscle problems in FM is, that this aspect of the disease is not better known.

Chronic Fatigue Syndrome (ME/CFS)

The results jive with those from Workwell’s two-day exercise studies which indicate that people with ME/CFS hit the wall after blowing through their limited aerobic energy production capacity.

In ME/CFS, the abnormally high muscle

conduction velocities seen in FM occur only after more force is applied to the muscle. While the authors stated that central nervous system activation may be involved in ME/CFS, they more pinned the blame on a breakdown in aerobic energy production and a subsequent quick entry into anaerobic energy production.

For years, two-day exercise studies have documented that people with ME/CFS are quickly blowing through a broken aerobic energy production – and finding themselves fatigued and in pain as their anaerobic energy tries (and fails) to keep up.

Some exercise studies do suggest that problems with energy production are present in FM, but it’s pretty clear that people with FM can generally tolerate more exercise than people with ME/CFS. This is the first study I’ve seen that might explain why. In FM, the central nervous system appears to be the chief culprit. In ME/CFS, a broken aerobic energy production systems is.

Dejurgen

Thanks Cort, as usual an excellent report on science I never heared of before.

“The authors proposed that the hyperactivated motor neurons in ME/CFS were associated with the activation of thicker, more anaerobic muscle fibers.”

Lately, I’ve been looking upside down on the issue of our muscles going very quickly into anaerobic functioning. Maybe that is the goal rather then a dysfunction. Sure, it isn’t a healthy response. Yet, it still may be a symptom due to the body attempting to prevent something even worse.

What are we talking about?

Since long, Issie has been working on the idea that excessive glutamate can cause the brain neurons (in ME patients) firing at far too high speed. That easily can create a hyper brain buzzing of activity and flashing thoughts and senses, but it all being rather unsynchornised and chaotic. That would easily lead to very high brain energy usage while creating a hyper but confused mind and sensory overload. What’s worse, the brain neurons risk to damage themselves in a process called glutamate excitotoxicity. That can permanently kill neurons.

Such uncoordinated overly buzzing brain can not only make thinking more on the edge, but muscle activation too quick and movements uncoordinated. We recently extended that idea with the “spinal cord escalator idea”, seeing good reason why an overexcited and inflamed brain can pass that inflammation downstream to the tissue like muscles and organs by having inflammation, oxidative stress and excessive levels of glutamate leak along the spinal cord to these tissue. Inflammation of inflamed tissue could equally well flow upward along the spinal cord to the brain, more precisely the brain stem where so many nerves start and end. The combination of the downward path and the upward path have potential to create a vicious circle.

Now we have stumbled on another likely odd mechanism: the inflamed brain, using so much energy so often, needs an increased supply of energy and oxygen. That means an increased amount of glucose (as few other sources of energy pass the brain blood barrier) and increased blood flow. Yet, other studies point to our brains having reduced blood flow at base and even less after exertion. And our RBC seem to be rather stuborn when it comes to release oxygen to the tissues.

A higher need for energy and oxygen and a poorer blood flow towards the brain combined with reduced oxygen release from the RBC isn’t an ideal combination to say the least. So, chances are reasonable our brains depent more on anaerobic energy usage then the brains of healthy people. That would mean an even bigger need to send plenty of glucose to the brain, for providing bits of energy per molecule of glucose converted to lactate. Research has found increased lactate levels (at least at times) in our brains too.

Our brains can produce some amount of energy by converting proteins into bits of energy too. Metabolic research however has shown that we tend to be low on blood protein too.

So it seems when our brains go on a wired frenzy, they often may need plenty of both glucose and amino acids and use much of it in a low energy yielding anaerobic process.

That is where the muscles come in. The liver has some glycogen storage, from which it can produce glucose to release to the brain. It is said to be able to store about 100 grams of it. The muscles can store up to 4 times as much, 400 grams. However, the muscles can’t release glucose to the blood stream. They lack the transporters to do so.

So, when the brain is craving for plenty of glucose, the smaller liver storage may get depleted faster then desired. Or it may not be able to convert glycogen to glucose fast enough. Or… there are a few more ways this could be insuficient at times.

When the brain really needs more glucose (and the liver can’t easy enough produce plenty of ketones), then the body quickly will have to turn to salvaging tissue for taking out the protein from it. As you can imagine, that is a rather harsh option on those tissue. So the body preferably will do that to “more repairable” tissue. Think about skeletal muscle and in second place connective tissue. There is plenty of protein in both.

Still, with muscle glycogen storage depots being four times as large as the livers storage, it’s a bit a shame the muscles can’t deliver glucose to the blood isn’t it? That holds even more for us, as most of us are crippled enough to be unable to move enough every and each single day to make a dent in those rich glycogen (if filled, of coarse) stores.

Now if there would only be a way to release that glucose. Well, actually there is, under conditions that is. Muscles are very well known to produce lactate from glucose quickly when working anaerobically and then dump plenty and plenty of lactate in the blood. Well, if that pathway isn’t broken, the liver excels at recycling that lactate to glucose. OK, the process is fairly inefficient. For each glucose converted to lactate the muscles receive 2 ATP. It does cost the liver however 6 ATP to recycle lactate back to glucose. But hey, if the alternative is to destroy skeletal muscle and connective tissue (EDS like?) to salvage enough proteins to save the brain… then it may be a fair price to pay.

All of a sudden, me waking up shivering and shaking violently with my limbs in the middle of the night makes a whole lot more of sense. Blood sugar at night can drop rather low. Blood flow gets worse. My brain feels like being in really bad trouble. If it are mainly my anaerobic (fast) muscle fibers shaking that hard, they convert plenty of glucose to lactate. The shaking and shivering is a good sort of pump to pump out that lactate to the blood and get it to my liver. The liver then can work extra hard to try and convert it to glucose for my brain. That does put a very high burden on my liver and on my breathing, especially if the brain needs plenty of it as it uses much of the glucose in an anaerobic and poorly efficient way. So me waking up and breathing like a horse in the middle of the night when I do that suddenly makes a lot more sense too…

So, our muscles going very quick into anaerobic mode: a bad dysfunction or an attempt to save our brains?

Part of the answer may be in this quote from what Cort wrote:
“Evidence of a kind of hyper-excited muscles in FM goes way back. A 1989 study…evidence of **twitchy** muscles which failed to relax or calm down between contractions.