Chronic fatigue syndrome from vagus nerve infection: psychoneuroimmunological hypothesis

[JaimeS]

I have never been able to find a decent exposition of the effective ranges of cytokines, because it does vary.

Also a surprisingly difficult thing to search for. I ended up on "how far do cytokines travel?" but it still didn't yield much.

I was surprised to see that this primer listed cytokines as autocrine, paracrine, or endocrine, meaning the affected body system is some distance away. Also, it may be old news to many, but here is actually an excellent primer on cytokines in general:

Inflammatory Cytokines in Non-Pathological States

Very good because it makes it clear that there is no clear-cut distinction between pathology and non-pathology - 15 y.o., so it may not be entirely accurate, but it's a good beginner's resource for someone like me who has been getting this info piecemeal and needs to patch in the rest!

-J

 

[Hip]

I hadn't seen the word endocrine used to describe a cytokine before, but it does make perfect sense, given that endocrine means "secreting into the systemic circulation". So IL-6 would certainly be described as an endocrine cytokine.


On another thread I was trying to connect Il-6 to the vagus nerve infection / sickness behavior theory of ME/CFS. IL-6 definitely plays a role in sickness behavior.

What's more, IL-6 levels in the blood increase by as much as 100 times after exercise (during exercise, muscles release copious quantities of IL-6 — IL-6 is also classed as a myokine).

So I thought this exercise-induced release of IL-6 might well explain PEM, if this IL-6 makes sickness behavior worse. So far though, I have not been able to fully connect the dots on this IL-6 PEM theory.

 

[Violeta]

Maybe if someone has leaky gut, a bacterial infection as a source of LPS, and a viral infection, the infection can spread fairly easily to wherever.

http://www.sciencemag.org/content/334/6053/245

And there's even a possibility that metals sequesters pathogens, different metal, different pathogen, drawn to a different organ or type of cell.

 

[natasa778]

I believe this is a reasonable hypothesis at this point. So how would one go about addressing a vagus nerve infection - or any kind of nerve infection?

-J

Just thinking out loud, my starting point being this finding that cutting the vagus nerve massively reduces risk of developing Parkinson's ... not suggesting anyone gets out their scissors and starts snipping their vagus away but wondering if things to stimulate/strengthen vn would help in these situation. Not to strengthen it 'to fight off infections' lol but to stimulate it as in 'lower its sensitivity threshold'. To lower its reactivity and production of cytokines when encountering infections/inflammation in the perietal nerves (or its own cells), and passing on those cytokines to the CNS. Things like deep breathing techniques (or even mad-sounding things like gargling and gagging exercises??) in the absence of over-the-counter VNS stimulators and magic antivirals?

This article mentions Érirú exercises for vagus stimulation. No idea if it is any good at all, anyone tried?

 

[JaimeS]

I hadn't seen the word endocrine used to describe a cytokine before, but it does make perfect sense, given that endocrine means "secreting into the systemic circulation". So IL-6 would certainly be described as an endocrine cytokine.


On other threads I was trying to connect Il-6 to the vagus nerve infection / sickness behavior theory of ME/CFS. IL-6 definitely plays a role in sickness behavior.

What's more, IL-6 levels in the blood increase by as much as 100 times after exercise (during exercise, muscles release copious quantities of IL-6 — IL-6 is also classed as a myokine).

So I thought this exercise-induced release of IL-6 might well explain PEM, if this IL-6 makes sickness behavior worse. So far though, I have not been able to fully connect the dots on this IL-6 PEM theory.

On a purely personal note, I've found it interesting that my cytokines are not dysregulated, or weren't at last draw. Totally mid-range normal, even though other pathogenic markers are distinctly 'off'. Then again, it wasn't measured during exercise.

I wonder if the genetic susceptibility is somewhere in a hypersensitive vagus nerve, as @natasa778 suggests. That would mean you wouldn't have to have elevated interleukins necessarily: you would either have elevated ILs or elevated sensitivity to them.

-J

 

[JaimeS]

Regarding vagus nerve stimulation:

Whoa: http://www.ncbi.nlm.nih.gov/pubmed/?term=vagus+nerve+stimulation

Also, raise your hand if you have persistent inflammation at the base of your skull/top of your neck.

I'll tell you one thing that got rid of it completely for a whole day:

...electrocution.

LOLz, right? I was getting a nerve stimulation test that was pretty horrifying - I mean, I was screaming, not just owowow - but afterwards, the pain at the back of my neck was completely absent. I stood up and said, "my neck doesn't hurt." The tech just stared at me all blase, like, lady, you were screaming a second ago. When I woke up the next morning it was nearly back to normal, but I had a blissfully pain-free day. Despite the screaming, I seriously wondered if I would consent to electroshock every morning. My '....no' was creepily tentative.

Acupuncture? Therapeutic mini-shocks? I'd seriously consider either one. It does make me wonder if some of what is causing the trouble is a polar molecule or a metallic ion...

-J

 

[JaimeS]

This article mentions Érirú exercises for vagus stimulation.

No experience, but the site looks distinctly shady!

 

[Hip]

Just thinking out loud, my starting point being this finding that cutting the vagus nerve massively reduces risk of developing Parkinson's ... not suggesting anyone gets out their scissors and starts snipping their vagus away

It occurred to me that one easy way to test the vagus nerve / sickness behavior hypothesis would be to temporarily anesthetize the vagus nerve using an injectable local anesthetic, much in the same way as a dentist anesthetizes your trigeminal nerve.

Anesthetizing the vagus would block the electrical signals that its sends to the brain when this nerve detects the presence of the infection-derived cytokines IL-1β and TNF-α.


Provided the vagus nerve was only anesthetized below the heart (so that heart function is not affected), then I think this would be safe. It would be like having a temporary truncal vagotomy, which is a standard medical procedure.

If temporarily anesthetizing the vagus reduced ME/CFS symptoms, then that would suggest the vagus nerve / sickness behavior hypothesis is correct.

 

[JaimeS]

It occurred to me that one easy way to test the vagus nerve / sickness behavior hypothesis would be to temporarily anesthetize the vagus nerve using an injectable local anesthetic, much in the same way as a dentist anesthetizes your trigeminal nerve.

Anesthetizing the vagus would block the electrical signals that its sends to the brain when this nerve detects the presence of the infection-derived cytokines IL-1β and TNF-α.

Provided the vagus nerve was only anesthetized below the heart (so that heart function is not affected), then I think this would be safe. It would be like having a temporary truncal vagotomy, which is a standard medical procedure.

If temporarily anesthetizing the vagus reduced ME/CFS symptoms, then that would suggest the vagus nerve / sickness behavior hypothesis is correct.

....uhhhh, who volunteers?

vagal block (vagus nerve block) regional anesthesia produced by blocking of vagal impulses by injection of a solution of local anesthetic into the vagus nerve at its exit from the skull.

Huh, apparently you can do it safely from the back of the skull without affecting the heart?

And then there's this, which ties directly in to my previous comment about getting relief when I was shocked with a high voltage.

Can the Nervous System Be Hacked?

After anesthetizing the animal, Tracey cut an incision in its neck, using a surgical microscope to find his way around his patient’s anatomy. With a hand-held nerve stimulator, he delivered several one-second electrical pulses to the rat’s exposed vagus nerve. He stitched the cut closed and gave the rat a bacterial toxin known to promote the production of tumor necrosis factor, or T.N.F., a protein that triggers inflammation in animals, including humans.

“We let it sleep for an hour, then took blood tests,” he said. The bacterial toxin should have triggered rampant inflammation, but instead the production of tumor necrosis factor was blocked by 75 percent.

Proposed therapy?

Why, yes, that IS an implanted electrical stimulator locked around the vagus nerve.

-J

 

[acer2000]

I have always wondered about damage to the vagus nerve causing problems. I got CFS after I had open heart surgery. There were a lot of variables in my case - hospital stay, blood transfusion, surgery, and then an illness that hit about 5 months after the operation. In the intermediary I developed migraines and "IBS".

The point is, there has always been concern about trying to avoid damaging the vagus nerve when doing surgery in that general area. Heart surgery is a particular risk.

From a practical perspective, I'm not sure how you'd figure out if you had damage though. Save gross dysfunction.

 

[Hip]

....uhhhh, who volunteers?

I would love to.

vagal block (vagus nerve block) regional anesthesia produced by blocking of vagal impulses by injection of a solution of local anesthetic into the vagus nerve at its exit from the skull.

I can't seem to find much info about this technique, and why it is used.

 

[natasa778]

Just remembered that they are now using a small vagus stimulator device to keep RA arthritis in check -working theory being that it helps dampen down inflammatory signals that then spread to joints etc.

Still early days but the results (if they hold) are nothing short of phenomenal.

http://www.huffingtonpost.com/2015/05/29/hacking-the-nervous-syste_n_7469526.html

Having found evidence of a role for the vagus in a range of chronic inflammatory diseases, including rheumatoid arthritis, Tracey and his colleagues wanted to see if it could become a possible route for treatment. The vagus nerve works as a two-way messenger, passing electrochemical signals between the organs and the brain. In chronic inflammatory disease, Tracey figured, messages from the brain telling the spleen to switch off production of a particular inflammatory protein, tumour necrosis factor (TNF), weren’t being sent. Perhaps the signals could be boosted?

He spent the next decade meticulously mapping all the neural pathways involved in regulating TNF, from the brainstem to the mitochondria inside all our cells. Eventually, with a robust understanding of how the vagus nerve controlled inflammation, Tracey was ready to test whether it was possible to intervene in human disease.

 

[JaimeS]

I would love to.

Brave!

I can't seem to find much info about this technique, and why it is used.

Me, neither. I searched around a bit (read: ten minutes) but couldn't locate why on earth anyone would want to do such a thing.

-J

 

[JaimeS]

Just remembered that they are now using a small vagus stimulator device to keep RA arthritis in check -working theory being that it helps dampen down inflammatory signals that then spread to joints etc.

Still early days but the results (if they hold) are nothing short of phenomenal.

http://www.huffingtonpost.com/2015/05/29/hacking-the-nervous-syste_n_7469526.html

Same study, @natasa778 , different article.

-J

 

[Hip]

There is, by the way, a new hand-held vagus nerve stimulator device called the Gammcore, which is detailed in this and subsequent posts. The Gammcore you apply to the vagus nerve in your neck. It is an alternative to the surgically implantable vagus nerve stimulators.


Though I am not sure if vagus nerve stimulation would help ME/CFS patients, if the problem is the vagus sending signals to the brain indicating an infection in the body/stomach, or in the vagus nerve itself, and thereby triggering sickness behavior.

In this case, you would presumably want to block vagus nerve signaling, rather than stimulate it.


Although electrical stimulation of the nerve may actually serve to partially block it, if the electric current is partially paralyzing the nerve on a temporary basis for several hours (as per @JaimeS's experience with feeling better after her nerve stimulation test, which I believe used an electric current).

If you can electrically paralyze the vagus to a degree, it should block some of the sickness behavior signals this nerve sends to the brain, and you may then feel better.

 

[MeSci]

Anyone tried a battery-powered 'massager' - or vibrator - on the neck or skull base? I don't have constant neck pain, but it is frequent, and sometimes the skull base too.

 

[JaimeS]

@MeSci

When I get a massage, or try a hand-held massager, it does feel good - but there's a limit. If the person pushes too hard or for too long, I begin to feel dizzy and sick to my stomach. It is not pleasant.

Apart from the pain of the shock itself, the electricity seemed to dissipate the problem instantaneously.

-J

 

[MeSci]

@MeSci

When I get a massage, or try a hand-held massager, it does feel good - but there's a limit. If the person pushes too hard or for too long, I begin to feel dizzy and sick to my stomach. It is not pleasant.

Apart from the pain of the shock itself, the electricity seemed to dissipate the problem instantaneously.

-J

I tried it this morning and started feeling very weird after a few seconds. Maybe it would be better applied elsewhere on the spine?

 

[JaimeS]

I tried it this morning and started feeling very weird after a few seconds. Maybe it would be better applied elsewhere on the spine?

....when I got it, it was on the LEG. But the voltage was HIGH. Really, really high. I couldn't complete the test.

When I got to the next autonomic testing post, I was nervous and shaky and asked for reassurance in some form. The two techs were like, "LOL! We switched from being techs over there because we couldn't take the screaming!" This test was the QSART, which uses a level of electricity that is best described as 'prickly'.

I have no idea what kind of voltage the initial test was, but let's say "high".

-J

 

[Snowdrop]

@MeSci
As for the base of the skull pain you probably know by now that for us ME peeps if we have pain that's a classic.
I'm sorry to hear if this is increasing for you.
I have no assess to much in the way of drugs and therapies but when this pain gets bad I just lay down and use an icepack and numb the crap out of it. Not an effective solution for long term relief but it dulls the pain at least for a while.

Also, the vibrator idea wasn't a bad choice to try. But it could have been too much.