Is PEM triggered by physical exertion the same as worsening triggered by sensory stimuli, cognitive exertion or emotions? What are the implications?

Trish

Trish

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Staff member
I have started this thread in order to reduce diversion of another thread where the subject arose.

Here are a couple of quotes from that thread:

Jonathan Edwards said:
I see nothing that indicates that anaerobic threshold is relevant. When someone wakes the next day, and the days after for weeks, feeling much worse there is no plausible reason why that should have anything to do with aerobic threshold being crossed some days before. And if PEM can be produced by bright light or travelling in an ambulance the whole aerobic threshold idea makes no sense. I am afraid that it is probably pseudoscience as much as the BPS theories. This is why I see the patient so much as wedged between two piles of nonsense.
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Jonathan Edwards said:
We have no understanding in biological or scientific terms what this exertion thing is. It isn't any of the things the physiologists like Workwell study - at all. Science has no concept of exertion in that sense. As far as we know it has nothing to do with using up calories or energy.
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My questions for discussion:

pwME experiences:

Is the worsening of symptoms triggered by sensory stimuli such as light and sound the same from a patient's perspective as PEM triggered by physical exertion in terms of symptoms and reduction in function? For example is it delayed or immediate, does it trigger the same extra symptoms, does it last as long?

The same question for heightened emotions, and cognitive effort. Do they trigger the same pattern of PEM as physical exertion does?

Science discussion:

Could there be different biological mechanisms leading to worsening of symptoms described as PEM resulting from different stimuli?

If there could be different reasons for worsening following sensory or emotional stimuli or cognitive exertion, compared with physical exertion that uses energy in a measurable way then why would the exertion causes PEM idea be nonsense?

Edited to include cognitive 'exertion'.
 
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I think this is an important discussion, thank you for opening this thread @Trish. I think one has to approach this topic with more ingenuity than we have seen.

I think one might also have to ask: What are the cognitive deficits pwME report or at least what is this "cognitive PEM" some pwME/CFS report and how does it tie in with the above question or is it irrelevant to the above question, respectively can this question be answered without having to open that can of worms?

One easy thing to note is that for those people with OI, that OI cannot be part of this puzzle. That is to say the phenomena can at most be the same as engaging in physical activity in a reclined position (like doing a 2 day CPET in your bed whilst lying down and having the bicycle turned around glued to the ceiling).
 
My first thought relates directly back to the thread title: There is an argument that says emotional stress and sensory stimuli result in forms of exertion, e.g., heart rate, breathing etc. Concentration and focus are forms of exertion, too. If anything, there may be a consistency between what many would think of as disparate processes or bodily properties not typically considered physical which nevertheless can result in PEM.
 
duncan said:
My first thought relates directly back to the thread title: There is an argument that says emotional stress and sensory stimuli result in forms of exertion, e.g., heart rate, breathing etc. Concentration and focus are forms of exertion, too. If anything, there may be a consistency between what many would think of as disparate processes or bodily properties not typically considered physical which nevertheless can result in PEM.
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I think the crucial part which has been alluded to is that they are forms of exertion that we don't understand very well, that is to say they are not really tied to any excessive use of energy in the sense of physics. That is to say, "thinking hard about something" doesn't require more much energy than just lying around. In which case all the ATP, mitochondrial, metabolic theories, aerobic threshold etc don't seem particulary sensible in these scenarios.
 
Trish said:
Is the worsening of symptoms triggered by sensory stimuli such as light and sound the same from a patient's perspective as PEM triggered by physical exertion in terms of symptoms and reduction in function? For example is it delayed or immediate, does it trigger the same extra symptoms, does it last as long?
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I've learned over the years to mitigate or often avoid PEM from overdoing things "physically" , that is walking, lifting etc, so I may be off in this, but it seems to me that those produce PEM in 48 hours or so. But emotional stress or heavy and prolonged concentration will total me within 12 hours, if not sooner.

I wish I could be clearer on the walking, lifting stuff, but I've become religious about observing my thresholds. Which is worse? They're all bad, but the relative immediacy of the emotional/cognitive penalties seem to weigh more heavily on me.
 
For me they are completely different phenomena. Cognitive exertion produces brain fog, which can be debilitating, but not PEM (except when combined with physical exertion). Sensory issues are painful & overwhelming stimuli that I have difficulty processing but have nothing to do with PEM. Emotional stress is not a factor. The only link to PEM seems to be physical exertion and the effect is both delayed and not 100% reliable. Could speculate about potential mechanisms although we have so little data it would just be pure speculation.

I suspect that many pwME haven't deliberately tried to test these things separately although I do seem to be in a small minority with not having cognitive effort trigger PEM?; I'd be interested to know how widely this is shared. Astonishing that after all this time we don't have hard answers to these questions from well-conducted research.
 
I have different responses to the different stimuli.

Exceeding my physical exertion threshold cumulatively over a day or more, or a single large exertion leads to delayed PEM that includes increased muscle pain, muscle weakness, debility, feeling more ill, increased nausea, loss of appetite, sometimes vomiting, new onset headache which may be migraine type or may not, dizziness, and significant loss of function, and brain fog, confining me to bed for a day or more and taking usually one to two weeks to return to my normal level of function and symtoms.

Exceeding my cognitive threshold is also causes worsening, but it's mainly cognitive worsening, both immediate slowing down and making more mistakes, and longer term fogginess lasting from days to a week or so. I don't get the same sort of delayed PEM from cognitive effort as from physical effort, but I think I may be unusual in this

I don't have serious sensory sensitivities to normal levels of sound and light to the extent of needing to wear eye covers or ear plugs, but do find loud sound and bright light more draining than when I was well. Bright light or flashing/moving light triggers migraines and loud sound of a fire alarm once made me faint. I can't watch TV programs that involve rapid changes in light intensity and movement. For example, I've had to give up on Strictly Come Dancing since they have turned it into a light and sound show with rapid moving and flashing light.

Emotions and psychological stresses, unless they involve a combination with physical exertion, don't for me trigger delayed PEM, as far as I know.
 
Nightsong said:
I suspect that many pwME haven't deliberately tried to test these things separately although I do seem to be in a small minority with not having cognitive effort trigger PEM?; I'd be interested to know how widely this is shared. Astonishing that after all this time we don't have hard answers to these questions from well-conducted research.
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You are not alone. I'm the same. My PEM that fits the definition of PEM including delay, worsening of all symptoms and new ones, as spelled out in my post, is, as far as I can see, entirely triggered by exceeding my physical threshold. I have tended to hold back from saying this when people are discussing cognitive PEM, so maybe there are more of us than we think.
 
A minor point about how travelling in an ambulance might result in PEM (as mentioned in the first post):
it is known that the vibrations of a vehicle cause tiredness. This article mentions a study where people sat in a car simulator with and without vibrations, and they became more tired with vibrations. The article writers suggest that it is something to do with activation of the parasympathetic nerves. I remember being told that it was because muscles are constantly making minute adjustments. I don't know what the cause is, but travelling in a car has been shown to be tiring for healthy people due to the vibrations. Perhaps it involves more exertion than is immediately apparent.

For me, emotional stress (negative or positive) does not cause PEM. Quite the opposite, if there is an element of novelty for example or heightened emotions, I sometimes seem to be able to do things that would normally cause PEM, without triggering PEM. Perhaps because of some adrenalin type of effect?

I personally haven't noticed light causing PEM. Do we really know that? Immediate discomfort, yes, obviously people with more severe ME/CFS get that. I think it might often be hard to separate a stimulus of light from other stimuli.
 
EndME said:
I think the crucial part which has been alluded to is that they are forms of exertion that we don't understand very well, that is to say they are not really tied to any excessive use of energy in the sense of physics. That is to say, "thinking hard about something" doesn't require more much energy than just lying around. In which case all the ATP, mitochondrial, metabolic theories, aerobic threshold etc don't seem particulary sensible in these scenarios.
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Perhaps, even if ME/CFS is very much tied into energy issues, PEM is triggered by something other than exceeding or insulting energy thresholds, e.g. heart rate or blood flow or vascular impairments of a sort.
 
duncan said:
Perhaps, even if ME/CFS is very much tied into energy issues, PEM is triggered by something other than exceeding or insulting energy thresholds, e.g. heart rate or blood flow or vascular impairments of a sort.
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I wonder if we wouldn’t have found a “cheat” medication that vastly increases your PEM threshold in that case. For example if it was heart rate, beta blockers.
 
Nightsong said:
I suspect that many pwME haven't deliberately tried to test these things separately although I do seem to be in a small minority with not having cognitive effort trigger PEM?; I'd be interested to know how widely this is shared.
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I don't get specific symptoms of cognitive dysfunction / brain fog. Even when crashed out my brain is active. Similarly I don't think I induce PEM from cognitive effort.

I definitely do have pathological fatigue, sleep disruption/failure, physical activity induced PEM, orthostatic intolerance, severe headache, sensory hypersensitivity, major gut disturbance etc. PEM causes more OI.

I do think energy generation will be at the heart of fatigue and PEM. Possibly OI too. One of my current mental models suggests —

Substance X is the something-in-the-blood.
Increased activity (eg muscle, neuron) increases resource demand.
As fuel resource is imported to meet demand, so substance X might also be imported into the cell (eg via membrane transporters)
Substance X in the cell impairs mitochondria +/- lipid membranes (external and internal)
OxPhos ATP generation is impaired with ETC uncoupling, producing more ROS, leading to fatigue and PEM symptoms, with a delay for ROS effects -> PEM
Over time intracellular substance x is cleared, with partial restoration of mito function, leading to resolution of PEM, reduction (partial?) of fatigue.

This is the sort of thing I'm wondering about given that the nanoneedle impedance findings are presumed to have been replicated (per Fatima Labood's comments back in I think June).

(Speculatively, perhaps substance X might be some form of early amyloid oligomer as recently reported on.)

I'll have a think about other possibilities, esp how different stimuli might take effect, but simplistically it might just be too much sensation = too much neuron activity as above.
 
People with PEM tend to have puffy faces, puffy eyelids. I am pretty sure that ibuprofen reduces my symptoms - and it reduces pain and reduces swelling. I understand that it works on prostaglandins. Women seem to be likely to produce more prostaglandins than men.

Prostaglandins work on G-coupled receptors, which we've seen talked about quite a bit in relation to ME/CFS. They cause pain and swelling.

I found this paper that reports finding that prostaglandins were produced in mouse skin cells 24 hours after exposure to UVB.

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE2, PGF2α, PGD2 and PGI2 (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE2, PGD2 and the PGD2 metabolite PGJ2. Twenty-four hr after treatment with UVB (25 mJ/cm2), production of PGE2 and PGJ2 increased, while PGD2 production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5 – 25 mJ/cm2) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE2 (EP1 and EP2), PGD2 (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.
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I need to sleep now. I haven't looked to see if the level of UVB is reasonable or off the planet large, or what the issue with 24 hours is. Is it just sunburn, or is the effect produced by more subtle exposure?
 
Hutan said:
I am pretty sure that ibuprofen reduces my symptoms - and it reduces pain and reduces swelling.
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This is the second time I've seen ibuprofen brought up recently, so on the off chance it's relevant, ibuprofen is basically the only med that reduces pain for me: headache, stomachache, sunburn, etc. Aspirin and acetaminophen do next to nothing. No effect on ME/CFS symptoms that I've noticed though.
 
Hutan said:
This article mentions a study where people sat in a car simulator with and without vibrations, and they became more tired with vibrations.
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Are we sure this is not sleepiness. Sleepiness with car vibration is surely something lots of people are familiar with. Both I and my wife fall asleep in a vibrating car but not in a train. The sleepiness is irresistible but nothing to do with tiredness. And of course some people feel sick with vibration and lots of people feel sick I a boat. I suspect these are vestibular effects, not to do with muscle.
 
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