Preprint A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma, 2025, Edwards, Cambridge and Cliff

What Arnoble is describing here is, to my knowledge, a phenomenon reported by a large number of patients. It might be worth taking note of it. It happens to me too—a 'burning spine,' most notably in the cervical region, has been described for a long time by many patients.

 

But that sounds different from Arnoble's symptom. The spine is probably the commonest site of pain in the body and it lights up when we are not well so I am not persuaded it tells us much.

 

I can't be sure, but I doubt that it's different from what Arnoble's wife (?) describes, it's a very distinct sensation. Personally, I wouldn't necessarily describe it as aching or painful, it's quite difficult to describe, I could see how people end up describing it as aching. It might very well be of no 'use', my intuition tells me otherwise.

 

This is the same for me also. I think this is very common in people with ME.
When I first got ill and was still working and was trying to explain my symptons of fatigue to disbelieving people, "so what, we all get tired!", it was only when I mentioned that I felt exhausted in the morning and that I progressively felt less tired as I worked through the day that I got a different reaction from them.

 

This is also very true for me.

 

Just checking I’ve got this right – you’re saying there is a faint possibility that the neuro signals are not false, and are actually contributing to the problem, possibly (Via interferon gamma receptors on synapses and neurotransmitter receptors on T cells).

But it sounds like it’s more likely the Neuro pain and fatigue, false signals, in the sense that they are not related to the pathology.

If that is the case, we go back to the original problem with neurovigilance that pushing through shouldn’t contribute to the problem. Yet the experience of many people is that it does.

I’m aware that I might not have understood correctly so I am asking to clarify.

 

Yep. There's a warm-up effect that would be great if it weren't for the fact that it overrides your ability to sense your limits.

Once you've broken through the wall of shakiness and heaviness, the warning system seems to be dialled right down until it becomes a near-emergency.

 

Yes, this is fairly normal for me. I usually feel like sh%t first thing, then generally grotty after eating, for about an hour or two, then gradually improve from about 1500.

 

Still, won't pushing through lead to more "false" signalling? And even if these signals are "false", aren't they still the cause of symptoms and limit our abilities? How could pushing through lead to any improvements in that case?

 

I don't really understand what you mean by false signals @Simon M . The pathology probably is the signals as far as I can see.

Edit: basically what Jesse said.

 

Yes and no - for me at least pain and fatigue and not the only thing that limit our ability. This goes to the heart of psychosocial and biopsychosocial views of the world and what we need to do to recover, at least as I understand them.

I hope I make more sense below:

Pain and fatigue exist to protect us from harmful activity. The CBT model and mind-body approaches work on the basis that 'hurt does not mean harm'—those signals mislead us. "False signals" is probably the wrong term. What I meant is that people mean the symptoms are real, but they give wrong information, and so we can ignore the pain and fatigue that are holding us back (and move ahead into a bright future...)

CBT is built on the idea that we focus too much on our symptoms, and what would feel like unremarkable pain and fatigue to a 'normal' person is perceived by us asd a major signal. Their solution is to ignore such symptoms and carry on.

Neuro hypervigilance is used by BPS as a twist on this: invoking an oversensitive/amplifying insula (a brain organ that plays a critical role in monitoring bodily functions and emotions), it is not overfocusing but some unhelpful feedback loop that has locked our brain into an unhelpful pattern. The answer is still to change our thoughts and behaviour.

My point is that if the (b)PS model is right, we can push through the pain and fatigue and make progress. (Mind body approaches often explicitly argue that changing your thoughts/behaviours rewires the 'flawed' neural pathways, e.g. NLP).

But my experience is that pushing through leads to functional loss (a relapse). But the functional loss is not because pain and fatigue are stopping me (they return to my 'normal' levels after a couple of weeks), it is muscle weakness, brain fog, etc.

That doesn't fit with a neuro hypervigilance model where the neuro signals are not contributing to the pathology.

See above. I am clearly confused, as I thought this:

Meant there is much more likely that the neuro is not signalling back, though it is possible. In which case it isn't contributing to the pathology in the sense of making the illness worse (in my experience, pain in particular, but also fatigue usually return to pre-relapse levels quite quickly).

It feels like we are going round in circles, so maybe I'll leave it there.

 

Here is her typical PEM sequence:
a) a feeling of "nausaa" in/around DRG at vertebra prominens (years ago there was also "weight" here, but less so in recent years); not vomit-nausea, rather malaise
b) MUST lie down pretty much immediately as her body feels like it will not support itself, not even in a chair
c) staying flat, the "nausea"/"weight" subsides over a half-hour or so, at least to a bearable level; the subsequent PEM can keep her feeling lousy for days/weeks/months - depends

This sequence has ALWAYS occurred, for 25+ years now, never occurred before the initial triggering infection, and can follow physical or mental "exertion" equally. She has no other co-morbidities and, prior to MECFS, was much more active and agile than your average person.

 

I think this is an area where thinking in psychobehavioral falls apart: the reason is not the function. Biologically, pain and fatigue serve those roles, constructed by evolution over millions of generations for reasons that promote survival. But it's not their function. Evolution is not concerned with individuals, and does not care about logic or making sense.

Neither pain nor fatigue follow some logic where some brain process has determined: oh no, this could be bad, must protect. They are autonomic processes that are complex at the macro level, but mechanistically simple at the level they act on. Attributing sentient-level organism behavior to them is tempting, and is the core of psychobehavioral ideology, but to me is as misguided as anthropomorphizing natural phenomena. Nature does not weep when it rains, however poetic it may sound.

BPSers love to work those things out along with thoughts and behavior, and although some small parts can be influenced this way, they would work out the same even if nothing beyond the primitive brain is involved. Lizards and other animals lacking a complex brain very likely behave 99% the same as us at the biological level, even if they behave slightly differently. Same for someone in a vegetative state.

There are always situations where pushing against either is necessary. In nature, walking on a broken leg, pain, to relative safety is necessary. So is continuing a long trek, fatigue, towards where food will be next season. Seeing them as protective in the psychobehavioral sense isn't much different from animalism, or seeing signs in tea leaves. All animals do the same. Without thought.

To me it's a lot like when people make analogies between government finances and a household budget. They are budgets in the general sense, but this is about the only overlap between either concept. It's not coincidence that pretty much all the core ideas in psychobehavioral beliefs originated in a time when superstitious concepts, such as ESP, ghosts, telepathy, astrology and so on, were very popular. They have the same idea of tacking on human behavior and motivation onto natural processes that, at the smallest level, are as purely automatic and indifferent to what intelligent beings think and believe as water freezing.

It's also quite similar to the concept of stress, which has many different meanings, such as cellular stress, or mechanical stress (and its counterpart: mechanical fatigue). Human culture has created overlaps in how we talk about those things, but they really have nothing in common outside of our perception and the limits of language.

 

As I say in my post #313 above, my wife experiences "nausea"/"weight" not "pain". Her sensation is an infallible prelude to PEM over 25 years, and there are no other co-morbidities or explanations. Innocent correlation does not seem to me to reflect her evidence.

 

Thinking further on this, clinical psychology, and neurology, are too focused on the neocortex, on human-specific intelligence, and not enough on the parts that actually regulate all this stuff, the primitive nervous system. They give far too much importance to thoughts and beliefs, which 99.999% of animals never had, as being central to how biology functions.

Working with the analogies of pushing through pain or fatigue for survival, there are many thoughts and behaviors that can influence what an organism, even a relatively smart human, will do. Thoughts and beliefs at the level of culture, such as choosing to stay in place because members of the tribe will surely come to help, or waiting for a sign from some deity or even choosing to see this as divine punishment, or perhaps following some beliefs that some have settled on, to go some place where food might be, or not, perhaps following a divine sign "observed" by attributing meaning to natural processes, how it's better to stay in place, to rest, and wait for magical providence.

Those thoughts and beliefs will definitely have influence in behavior, will even overrule it. This is one applicable way for thoughts and beliefs to influence a whole organism. Steve Jobs basically chose to die because he made some attributions out of behavior, mostly what he chose to eat, and how the influence biological processes.

But taking those ideas further, into beliefs creating or curing illness, the entire point of psychosomatic ideology, is just a completely different set of assumptions. Not too coincidentally, the kind of assumptions that can see religious figures carved into toasts, but applied to biology instead.

 

I am shamefully ignorant about nerves, but:
a) what about sensory innervation of structures near the DRG (e.g., spinal meninges)
b) what about innervation of the blood vessels supplying the DRG

I mis-described it - apologies - please see #313 above for a more considered description, of nausea/weight rather than ache.

She has no "dodgy bits of back" or other co-morbidities. Even so, how would a dodgy disc light up from immune signals elsewhere?

 

Hi Jesse thanks for bring up my question again & asking it in a more useful way

that’s exactly what I was trying to ask! and thanks Jonathan for answering am so encouraged by yr response I always thought the significant positive impact of stress to be so odd & the way PEM will be delayed (for a while at least) UNTIL I calm down (sufficient to sleep) to be a strange phenomenon.

it certainly makes a bit of a mockery of the “brain retraining” fan club’s ideas that our systems are stuck in ‘fight flight’ mode. I wish mine were!

edited to add: just in case - that was a genuine thank you @Jesse not sarcasm. and welcome to S4

 

By and large stimulation of nerve cells and also tissues around them - as occurs when a disc presses on a nerve root and surrounding meninges and blood vessels, very close to DRG - just gives you pain in the part the nerve supplies. For sciatica that is the foot. For cervical spondylosis it is your thumb or fingers.

Everything I now about neurology tells me that it is extremely unlikely that symptoms felt near DRG have anything to do with the DRG. That doesn't mean that DRG are not involved in ME/CFS but if they are that is not going to be how it shows itself.

I hear what you say about the symptoms your wife has. I think that may well be additional evidence that immune signalling is going on - rather than either faulty mitochondria or psychosomatics - so of interest, but for other reasons.

The immune signals we are interested in tend to work by sensitising nerves so that stimuli that would normally be experienced as touch or movement are experienced as unpleasant. Since we all have dodgy discs at the vertebra prominens (the worst is usually c5-6 just above) and in the lumber region we can expect to get pain or other unpleasant feelings in those places when we have an infection or an immune disease.

 

so it would easily explain why people with very severe ME\CFS have such acute sesitivity to touch ?