Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment, Robert K Naviaux, 2018

[lansbergen]

The whole ME scientific community is pretty much agreed that we do not find any damaged structures in the sense that might 'heal'.

Depends on how damage and heal are defined.

Damaged structures is not the only damage that can occur.

 

[Wonko]

Possibly not that helpful, as it's "subjective", but my body feels pretty damaged - it certainly doesn't feel undamaged.

It seems likely that the scientists/doctors are using a different definition of "damage" than I would use i.e. if something doesn't work properly, and there is no user error, then it may be broken/damaged. Simply coz looking at it doesn't reveal a broken bit doesn't mean it aint broke.

 

[Jonathan Edwards]

It seems likely that the scientists/doctors are using a different definition of "damage" than I would use i.e. if something doesn't work properly, and there is no user error, then it may be broken/damaged. Simply coz looking at it doesn't reveal a broken bit doesn't mean it aint broke.

I think most of us use damaged to mean something a bit more than not working properly.

If one of the drawers of my tool cabinet will not open it is usually because the hammer has rolled over and its head has jammed the drawer shut. That is not damage. But if the drawer bottom falls out because the sides have come unglued that is damage.

The hypothesis about healing very much implies damage in the specific sense of something that needs repair or mending (fibrosis, scarring) rather than something out of line. Autoimmunity is not damage (even if it can lead to damage). It is the immune system getting caught up in itself.

I think the relevance of this is that treatments aimed at healing of the sort that is useful for damage are not very likely to help problems that are due to things being out of line. For things being out of line you need specific methods for putting them back in line - and those will be different in each case.

 

[Wonko]

Being pedantic - I would classify your hammer example as user error (improper tool storage).

I accept that you have a point of view, shared with others, as to what constitutes damage, and that your, and their, opinions on this carry more weight than mine.

This is probably because you appear to be using an objective definition, whereas I am using a subjective one, as I experience it subjectively, and it feels like repair, if available, would be a tremendously good idea, from a purely subjective point of view.

 

[Trish]

Perhaps a simplistic parallel would be the pain I experience in my muscles from my ME and the pain I experienced when I broke a bone in my shoulder. The pain felt quite similar once the initial very intense pain of the fracture decreased. The morphine I was given at the hospital for the broken bone reduced my experience of both types of pain but did not remove either.

But the shoulder pain was due to structural damage that could be seen on Xray, and gradually repaired and the pain went away completely. From that I deduce that there is nothing wrong with my bone 'healing cycle'.

The ME muscle pain never goes away, though it fluctuates according to how much I have used each particular muscle. Yet there probably isn't any physical damage causing the ME pain that can be measured or repaired. It is probably caused by biochemical imbalances of some sort that might cease if the root cause of my ME could be reversed. What that root cause might be, I have no idea.

And now I've written that, I have no idea whether it has any relevance to this thread. Ah well...

 

[lansbergen]

The ME muscle pain never goes away, though it fluctuates according to how much I have used each particular muscle. Yet there probably isn't any physical damage causing the ME pain that can be measured or repaired. It is probably caused by biochemical imbalances of some sort that might cease if the root cause of my ME could be reversed.

Mine sometimes goes away now if I stop soon enough and rest.

Even when I have done a bit to much a 500 mg tablet paracetemol can make it go away now.

It took me 20 years of immune modulation to get where I am now.

In my book the immune response causes damage. That is normal and it usely will heal fast. It is transient damage but none the less damage.

In my opion the immune system does not work the way it should. Somewhere in the route something goes wrong.

I am pretty sure the immune modulator I take, helps the immune system go back on track.

 

[Mij]

It seems likely that the scientists/doctors are using a different definition of "damage" than I would use i.e. if something doesn't work properly,

I think dysfunctional is a more appropriate term.

 

[Sean]

Interestingly, despite the millions being spent in testing, a simple test such as Total Bile acids has never been performed in any of the studies to the best of my knowledge.

Probably true for a whole range of fairly straightforward, if mostly non-routine, testing. Just hasn't been done, or the rare papers that do look at stuff were 1) too under powered for a robust finding, 2) didn't look at it in the right way, or 3) a single study that has never been done again to refute/confirm/refine/expand.

I sometimes wonder if, among the decades-long blizzard of words and assumptions and inferences thrown about from all sides, and the fancy high tech wizardry increasingly being applied to the task, we are missing something very basic in all this.

(Not in any way slighting or discouraging the high tech stuff. It may well give us the answer, or at least a critical clue or three, and it definitely should be done.)

 

[mariovitali]

I sometimes wonder if, among the decades-long blizzard of words and assumptions and inferences thrown about from all sides, and the fancy high tech wizardry increasingly being applied to the task, we are missing something very basic in all this.

I second that.

And to be more specific i believe that a very unfortunate assumption has been made : That since we do not have elevated Liver enzymes, this means that there is no Liver involvement in ME/CFS pathology.

Interestingly, Coxsackie B, EBV, Cytomegalovirus, HHV-6, Echovirus, Parvovirus they all can potentialy result in Liver Injury.

 

[Inara]

I second that.

And to be more specific i believe that a very unfortunate assumption has been made : That since we do not have elevated Liver enzymes, this means that there is no Liver involvement in ME/CFS pathology.

Interestingly, Coxsackie B, EBV, Cytomegalovirus, HHV-6, Echovirus, Parvovirus they all can potentialy result in Liver Injury.

But you should see this on an ultrasound or MRT of the liver?

 

[mariovitali]

@Inara

The following is a Fibroscan of a female ME/CFS Patient which suggests she has very significant Liver Fibrosis. Most importantly this patient did not have any elevated Liver enzymes at any point.

The gold standard of assessing the Liver is Liver biopsy from multiple sites. Not an easy test to perform so Fibroscan is the next best option.

 

[dannybex]

@dannybex do you have candidates in mind? The only thing I'm aware of that might qualify is the recent brainstem findings (here).

Last I heard Ron Davis et. al were exploring, among other things, a 'metabolic trap' hypothesis to which any notion of 'damage' seems pretty tangential.

Look, here's my thinking on this, which is absolutely not the gospel:
-Clearly ME bodies are profoundly dysfunctional. So much so that quality of life can be much worse than for some other very nasty chronic diseases.
-Tests notably don't reveal damage to patients' bodily structures. Surely some individual patients have abnormal findings but there isn't anything consistent between patients.
-This combination seems 'distinctive' to me. It is my understanding that the tools/methods/frameworks we have available to us are pretty adequate for finding what could be reasonably called damage. So we should heed the findings. Certainly we are not there yet when it comes to identifying 'changes' that lead to profound symptoms, so maybe we should keep working on that. In the end, though, many things are possible because we're all in the dark.

Certainly we all have different definitions of the word 'heal'. Personally, when I think of 'heal', I mean 'to rebuild, repair, or make healthy or whole again'. Others obviously have other definitions.

Naturally there "isn't anything consistent between patients", because it's probably very likely we got sick in different ways. That's what I've seen and heard from patients over a 20 year period, including those who have recovered or gone into remission. They all had different triggers/causes. So patients will have different issues, different things that need to 'heal' before health can be fully restored. In that vain, the following come to mind:

The gut (in cases of intestinal permeability or dysbiosis)
Muscle degeneration/loss (elevated 3-methylhistidine has been found in 2 or 3 studies)
Immune dysfunction or chronic immune activation
Peripheral neuropathy
Mitochondrial function
Cardiac and cardiac-related abnormalities
Brain/brainstem abnormalities
etc....

I sincerely don't appreciate this.

I’m sorry you were offended, of course that wasn’t my intent. It just seems that those who are bedridden – so horrifically weakened that when or if they try to stand up, they pay for it later with full-body convulsions for hours, even days afterwards – that that will never change until their bodies are able to heal, to repair, to rebuild – in whatever ways possible.

 

[dannybex]

I accept that you have a point of view, shared with others, as to what constitutes damage, and that your, and their, opinions on this carry more weight than mine.

I'm not sure why you would consider your opinion to have less weight @Wonko. It's just as valid as anyone else's, at least in my opinion.

 

[Wonko]

I'm not sure why you would consider your opinion to have less weight @Wonko. It's just as valid as anyone else's, at least in my opinion.

I am not a professor, an academic, a scientist or even an MD. It could be argued that the opinions of those better informed than I, with more decades experience, who can actually think.....lol

 

[Barry]

@James Morris-Lent, you might try telling that to Jamison Hill and Whitney Dafoe.

Also not sure where you're getting the info that one of 'the distinguishing features is that nothing is actually damaged'. Could you provide a link for that rather odd claim?

Thanks in advance.

Maybe it's more akin to an old-fashioned clockwork clock with a pendulum. You can stop the clock by simply stopping the pendulum from swinging with your finger. The clock is not damaged, but is certainly not working very well.

Edited for clarity.

 

[Barry]

Being pedantic - I would classify your hammer example as user error (improper tool storage).

Does it actually matter? Whether a body is malfunctioning due to actual physical damage, or calibration that's gone skew whiff, or something that's crashed and needs rebooting ... the actual mechanism will make a difference to how treatment might be effective. If it is that damage per se is not the fundamental problem with ME, then investigations into repairing damage are not going to help with ME. If.

 

[dannybex]

I am not a professor, an academic, a scientist or even an MD. It could be argued that the opinions of those better informed than I, with more decades experience, who can actually think.....lol

It could also be argued that ME docs will tell you that it's your experience and opinions that have helped them understand and study the illness. That opinion and experience is important.

 

[arewenearlythereyet]

I’m reading this discussion on pain vs healing with interest despite my flippant remarks about the quality of this theory/paper/fantasy novel.

I think of pain as a sensory experience in the same way as we process and interpret any message (vision, sound, taste/smell etc)

pain doesn’t equate to damage necessarily ...it equates to your brain giving you an interpretation of the messages that it receives from the body.

So is it possible that we have pain with no injury? I think there are lots of examples of confused messaging in other conditions ...perhaps this is the case with us?

I deal with joint and muscle pain every day like most of us do and quite severe peripheral neuropathy (can’t turn pages of a book etc). I am not convinced though that I can categorically link this to damage that needs to be repaired? It might be a signal of damage but it equally might be misfiring pain receptors or incorrect perception of mixed messages without injury?

I think we as patients should tread carefully and not over interpret meaning to symptoms based on feelings without evidence or overanalyse symptoms as sometimes happens ...e.g. having gi symptoms means microbe gut infection/allergic reactions to food or feeling poisoned means we have a toxic liver problem/lead poisoning etc.

We should demand evidence for statements like this and weigh up lack of evidence as much as positive evidence. And quality of evidence is just as important for our pet theories as it is for BPS theories. I don’t think that compromises doctors listening to patients or anything...I’ve seen this argument thrown around when pwme don’t like facts that conflict with pet theories....unfortunately this is not evidence..sooner or later you need hard facts that prove the theory...and patient testimonials are only that ...a subjective set of perceptions open to interpretation.

I’m trying to keep an open mind about pain and damage but so far there doesn’t seem to be much evidence of damage apart from maybe peripheral neuropathy...but even then there would be nerve conduction indications that prove the nerves are not working and I don’t think there are any studies that prove this? Perhaps there is a study on this?

I’m not sure whether that makes sense or not? It’s a bit late for me.

 

[James Morris-Lent]

pain doesn’t equate to damage necessarily

It might also be worth noting that there can be damage without pain/'disease'/dysfunction

So is it possible that we have pain with no injury? I think there are lots of examples of confused messaging in other conditions ...perhaps this is the case with us?

My amateur read is that bad messaging is at the root quite a few chronic illnesses, particularly autoimmune, but also e.g. T2 Diabetes (insulin resistance). But ME seems so distinct in that there is no pattern of damage that results - such as MS lesions, arthritis, Diabetes complications, the 8,000,000 different things lupus does, etc. - not to mention normal blood tests.

I think we as patients should tread carefully and not over interpret meaning to symptoms based on feelings without evidence or overanalyse symptoms as sometimes happens

From what I can tell enough patients have made a good enough account for our individual symptoms that doctors have been able to put together reasonable guidelines that delineate the useful disease entity 'me/cfs', so we can all slap each other's backs heartily. I think everybody can be excused for making incorrect interpretations; most of us knew nothing much about medicine when we became ill, found no answers and got hit with a bunch of BPS equine refuse from a disturbingly high proportion of doctors. But certainly when it comes to pursuit of scientific understanding or advocating for changes in institutional policy everything put forth ought to be as correct and sturdy as possible (beginning with the fact that, whatever it is, people are having a hell of a time with this condition).

 

[Mithriel]

Paul Cheney spoke about his heart transplant. He said that once he got his new heart it took almost two years before he felt completely well, despite the heart working efficiently from the very start. This was because it took that long for the rest of his body to recover from the previous damage.

At the very least I am sure this will happen in ME even if there is a simple switch as Ron Davis thinks. After many years of illness, I am overweight and unfit which I would not have been if I had been well. I have diabetes which I believe was influenced if not directly caused by ME. Neurological problems and neuropathy are caused by ME and there is no going back.

We do not get proper testing for ME so it is not possible to say there is no actual damage done. The secondary consequences of diabetes are only seen as the result of diabetes because the disease is followed. Those of us with ME have additional diagnoses added on yet a lot of us share them. I wonder if we are faced with "there are no structural problems in ME so if you have some it can't be caused by your ME"

In one sense it is all academic but saying there is no actual damage feeds into the FND/MUS script of no structural damage so it is functional which in this sense means hysteria.