A Thought Experiment on Muscles

[Evergreen]

Was that a single muscle group study? The abstract talks of Vo2 max changes. It also seems different from other CPET studies in that day 1 was low.

Yeah, they did two things, a fitness test, and then, 4-6 weeks later, 3 bouts of plantar flexion exercise, albeit in quick succession:

Subjects performed 3 · 180 s bouts of plantar flexion contractions at 35% of MVC with each bout preceded by 60 s of rest and followed by 390 s of recovery. Phosphorous spectra were collected at 10-s intervals, as previously described [28]. Quantification of spectra was undertaken using the jMRUI software [32] with metabolite concentrations and metabolic calculations performed as described previously [28]. In particular, we evaluated the time required postexercise for pH to return to within 0Æ01 units of baseline levels and the time postexercise when maximum proton efflux occurred. These times were summed for each individual for the three bouts to form a total pH recovery time, and total time to maximum proton efflux.

I'll email you a copy.

 

[Jonathan Edwards]

sorry, that’s a bit of a list of my dances about the data. But I’m not sure how much weight this finding can bear

That is very much my perspective.

I ask the question because I think it is critically important for us to know what reasons we have for thinking that signals provoking PEM (the whole point of all this) are arising because of use of one or more muscles and their mitochondria and arising within that muscle. Maybe there is nothing going on in the muscles. Maybe the signals are arising in blood vessels, nerves, lymphoid tissue, fascia or wherever.

And I think a useful question to ask is what is happening in ordinary viral myalgia. A brief search of the net suggests that nobody really knows or has bothered to enquire closely. It is just assumed that some circulating cytokines do it.

 

[boolybooly]

OK, questions like this are worth asking ... and then answering.

CPET means Cardiopulmonary Exercise Test ? (Not computed positron emission tomography.)

Interesting idea about localisation of testing per muscle groups. Makes me wonder if it might even be possible to do this in vitro, if as has been reported ME patient plasma has the ability to induce ME in other cells. Big IF but if you could use PWME plasma to give a dissected animal muscle model ME for example, stimulating contraction via nerves. I know its a bit mean but I had a chicken wing for lunch, so no meaner than that.

Since you mentioned thought experiments, I hope this includes subjective reflection as it just so happens I am having PEM today from 20 mins pruning cotoneaster and holly in my garden yesterday. I felt rough afterwards and knew I had passed the threshold for a PEM response.

Sure enough PEM is here 24 hours later. The feeling is primarily systemic, a bit fluey as one would get from an immune challenge, most notable symptom is a mild ache in the middle of my head and sense of a dearth of energy and impending headache if I push it, which I may be able to avoid if I am careful to pace and rest, as I did stop after 20 mins yesterday, so this is the mildest PEM I can have and still notice its presence.

Which tells you something as it is not all or nothing, it is scalable.

Also muscle ache and sense of weakness relating to arms which I used for pruning and carrying. Am having to rest my wrists on the wrist board of my keyboard to be able to type for example. Legs feel OK but I know exertion elswhere will combine with the existing PEM and add to the systemic component.

There is a sense of energy debt at my core and from experience I know if I push it when I am like this I will suffer as there is not much freely available energy to draw on. If I exert in any way I will draw on more of the energy debt, whatever that is and that will make recovery longer and risk of headache and other symptoms like heart arrhythmia and squits more likely and then more severe.

So I think it is a mix of both systemic and localised symptoms. What I don't know is how the systemic symptom is manifested, is it in the blood or the nervous system or both? Does it switch cellular metabolism somehow? Does that apply only to the cells in muscles exercised or the whole body? I dont know.

I might try to think about this in two days, when the PEM effect should have lifted and it might be easier to think, if I behave myself.

 

[Sasha]

I ask the question because I think it is critically important for us to know what reasons we have for thinking that signals provoking PEM (the whole point of all this) are arising because of use of one or more muscles and their mitochondria and arising within that muscle.

All sorts of routes seem to lead to an experience that looks like the PEM from muscular exertion - those routes include mental effort, strong emotion and exposure to sensory stimuli including light, smell, sound and touch. So I'm wondering whether we should be looking for something upstream of the muscle. (As ever, please bear in mind that I'm no biologist and I don't know what I'm talking about.)

 

[Creekside]

But my impression is that people think there is a change in muscle with use.

Has anyone ruled out neurological effects? Maybe something in brain or nerve function affects muscle function. Could it be some effect of immune cell changes, such as the first muscle exertion primes some cells, which then inhibit muscle function later?

Just wanted to throw in that for me excessive cognitive or emotional exertion can mean that I’m generally less able in my whole body,

I don't know whether cognitive-induced PEM reduced my muscle function, but it sure made me not feel like doing physical activities. That might be an interesting experiment: test muscle function of people with cognitively(or emotionally)-induced PEM.

 

[rapidboson]

I think that was just one off grip strength?

As per methods:

Hand Grip Strength Measurement
HGS of the dominant hand was measured using a digital hand dynamometer (EH101, Deyard, Shenzhen, China) in two separate sessions. Rest time between sessions was 60 min, in which no strenuous physical activity took place. Patients sat in an upright position facing a standard table during measurements of HGS. The forearm of the dominant hand was placed on the table in full supination holding the dynamometer. Under supervision and verbal motivation, the handle was pulled 10 times with maximum force for three seconds, followed by a five-second relaxation phase. Before starting the measurement, the participants were shown two separate demonstrations of how the dynamometer should be used. The dynamometer displayed the highest value reached within these three seconds (measurement in kg), and this single value was then recorded. The attempt with the highest reading out of ten repetitions was recorded as the maximum strength (Fmax), and the average force (Fmean) of each session was calculated. Fatigue ratio (Fmax/Fmean), a measure of the decrease in force during one session, and recovery ratio (Fmean 2/Fmean 1), a measure of recovery of force between both sessions, were calculated.

References 8, 12,13,14 are about the same topic apparently.

 

[Evergreen]

Here's figure 4 from Jones et al. 2011 for anyone who is interested. This shows pH at rest (a) and after each of 3 bouts of plantar flexion exercises (b), (c), (d) separated by breaks of 6.5 mins/390 seconds:

You want to look at the black "Norm CFS/group 1" bar compared to the white controls, as the black group is the patients who exerted themselves adequately.

 

[Simon M]

I think it is critically important for us to know what reasons we have for thinking that signals provoking PEM (the whole point of all this) are arising because of use of one or more muscles and their mitochondria and arising within that muscle. Maybe there is nothing going on in the muscles. Maybe the signals are arising in blood vessels, nerves, lymphoid tissue, fascia or wherever.

I think a common experience is that PEM feels the same where it was triggered by physical or mental exertion. I guess one possibility is its mitochondria overload in the brain or in muscles, but perhaps Exertion in either organ (Muscles, cancer or organs, collectively) trigger a more generalised response. Possibly the same one as viral myalgia?

 

[rapidboson]

I remember some studies that have shown damage (?) to the mitochondria in specific areas of the muscle, maybe the sarcolemma or sarcomeres (something like that) but not all througout the muscle fibers?
Does that ring a bell?

I think it's this study

https://pmc.ncbi.nlm.nih.gov/articles/PMC10855807/

 

[V.R.T.]

I think a common experience is that PEM feels the same where it was triggered by physical or mental exertion. I guess one possibility is its mitochondria overload in the brain or in muscles, but perhaps Exertion in either organ (Muscles, cancer or organs, collectively) trigger a more generalised response. Possibly the same one as viral myalgia?

Yeah I've gotten muscular PEM symptoms and joint soreness from mental overexertion on many occasions.

 

[Utsikt]

Yeah I've gotten muscular PEM symptoms and joint soreness from mental overexertion on many occasions.

Me too!

 

[Kitty]

I only know the difference in what it feels like.

When I get up from sitting on a rested day, my leg muscles are reasonably willing. Getting up hurts and feels as if the muscles are being pushed hard, but it's not enough to make me reluctant to do it. For very short distances—a few paces—I can walk in a way that my rolling gait isn't obvious.

With PEM the large muscles judder unsteadily into action, and I can't get up without using both momentum from a rocking action and a push-up using my arms. My legs feel shaky all the time I'm standing; I walk from the hip with the legs almost straight, so I have to rock from side to side even more than usual. I think I keep them straight because it feels as if they might give way if I bent them to achieve a more normal gait.

Why this happens, I've no idea. It feels like a mixture of reduced power and reduced control, but I don't know how much of the latter is the cognitive impairment of PEM. I lose the ability to judge spatial relations, which makes me feel more at risk of falling; that sense of unsteadiness might affect my gait.

 

[hotblack]

To elaborate on an earlier comment. Some questions I have had for a little while, in an individual

• Does maximum hand grip strength vary over time with symptoms
• How long do you need to wait between subsequent single grips to not see the drop off in grip strength seen in multiple grips
• After a drop off in multiple grips is seen how long does it take to return to the baseline/maximum

These would seem to give an idea of correlation, triggering patterns and recovery. Something where testing after cognitive load (that feels like it triggers things in my body) could be interesting too. Also just the process of testing in a non ‘loaded’ environment (i.e. not a lab with lots of stuff happening) could be interesting.

I thought of getting a dynamometer and doing some self experimenting. The medical grade ones are very expensive though and I’m not sure how accurate the cheap ones are.

The question is, do people think something like this would tell us anything useful?

 

[Utsikt]

Does maximum hand grip strength vary over time with symptoms

For me it does. There are drastic differences between my strength on a good day and bad day. On bad days I struggle with lifting a glass. On good days I can pour water from a large bottle with one hand.

 

[jaded]

Alain Moreau did some work trying to induce pem with a small device contracting the muscle. I can’t remember much more and am too crashed to look into it to say exactly what it was in detail.

But I remember it triggered the release of certain micro-RNAs which could have downstream effects on the vasculature.

 

[ME/CFS Skeptic]

This is just personal anecdote, but in my experiences there is something that goes wrong in the muscle.

It feels like the lactic acid feeling you get after a long run but from doing simple tasks (that take a while). I got this early on in my illness when I wasn't deconditioned yet and still better at sprinting and weight lifting than my peers. But I would get this lactic acid feeling from riding my bicycle to school or repeatedly folding napkins, easy things that did not feel like an exercise for healthy people.

For me personally, the duration and intensity of the task is crucial. The abnormality is not that clear in short and intense burst of activity but in longer and repetitive taks that require some muscle endurance. So I hope that ME/CFS researchers will study this using a less intense but longer task than CPET.

I realise this is not representative for all ME/CFS patients but I've several heard others say the same thing so perhaps there is a subgroup with this phenomenon.

 

[hotblack]

For me it does. There are drastic differences between my strength on a good day and bad day. On bad days I struggle with lifting a glass. On good days I can pour water from a large bottle with one hand.

I have absolutely the same. But I’ve never measured it
I find coordination can be another good signal, but I don’t know of a way to measure that… maybe a dartboard!

It feels like the lactic acid feeling you get after a long run but from doing simple tasks (that take a while).

I may have similar. There are certainly times when a trivial activity can cause what feels maybe like what you describe in muscles I’ve used, but then it can spread throughout my whole body, it’s an odd sensation but I know a sign of bad things to come. Other times the activity can be… fine.

 

[richie]

I believe Fluge and Mella are working on something along those lines. They asked for pwME (CCC, probably >=moderate due to in person) and healthy controls last summer. Afaik, they got as many people as they needed.

Although I’m not sure what they will be measuring.

You can see the device here:

I understand that to mean "Will yu gi us an 'and" and we have farmers in the area by names such as Lund

 

[richie]

That is very much my perspective.

I ask the question because I think it is critically important for us to know what reasons we have for thinking that signals provoking PEM (the whole point of all this) are arising because of use of one or more muscles and their mitochondria and arising within that muscle. Maybe there is nothing going on in the muscles. Maybe the signals are arising in blood vessels, nerves, lymphoid tissue, fascia or wherever.

And I think a useful question to ask is what is happening in ordinary viral myalgia. A brief search of the net suggests that nobody really knows or has bothered to enquire closely. It is just assumed that some circulating cytokines do it.

This is the proposal in sarcoidosis but the puzzle is whence the cytokines if the granuloma are gone.

 

[richie]

My experience has been muscle "firing" after trivial exercise (formication, fasciculation", extended periods of stiffness and acidy feelings. I wonder if failure to repair muscle due to altered sleep is a factor at all. As a Pompe disease carrier who was prescribed vitamin D to make the most of an insufficient enzyme I do wonder about any role for autophagy.