1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Brain Cells Making us Sick? The microglia connection in ME/CFS & Fibromyalgia
Simon McGrath looks at theories that microglia, the brain's immune cells, could trigger and perpetuate the symptoms of ME/CFS and fibromyalgia.
Discuss the article on the Forums.

One Theory To Explain Them All? The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome -

Discussion in 'Latest ME/CFS Research' started by est_sunshine, Dec 28, 2013.

  1. est_sunshine

    est_sunshine

    Messages:
    23
    Likes:
    21
  2. barbc56

    barbc56 Senior Member

    Messages:
    1,235
    Likes:
    615
    It would be very unusual for one condition to cause all of our illness. But maybe a subset? I need to take a closer look at the article as right now I am way behind in my reading.

    Thanks for posting this.
  3. alex3619

    alex3619 Senior Member

    Messages:
    6,579
    Likes:
    9,522
    Logan, Queensland, Australia
    The vagus nerve hypothesis comes up from time to time. There is good evidence for some of it, but it will be interesting to read if they cite anything new. Viral infection of the nerves is also a leading hypothesis for a common complication in fibro and ME, small fiber polyneuropathy. It would also explain why antivirals work, but its harder to explain why Rituximab works using this model.

    PS I first read of a vagus nerve hypothesis in about 1993 but in connection to type 1 diabetes.
    Plum likes this.
  4. est_sunshine

    est_sunshine

    Messages:
    23
    Likes:
    21
    I think the gist is that several infectious agents including the herpes virus and other bacteria are capable of infecting the vagus nerve which can lead to a chronic immune activation which will keep the body reacting as if it has a large scale infection.
  5. est_sunshine

    est_sunshine

    Messages:
    23
    Likes:
    21
    Yes it still doesn't offer a treatment plan that targets the infectious agent. Hope you're feeling better Alex :)
  6. SOC

    SOC Moderator and Senior Member

    Messages:
    4,891
    Likes:
    5,361
    USA
    Interesting theory that could explain a lot about CFS (Fukuda, Empiric) or FM, and maybe ME/CFS (CCC, ICC). I hope we see more work on this hypothesis!

    I'm a little puzzled by the idea that the cytokines are only localized and not in the blood. Immune studies have shown both immune cell abnormalities (NK cell abnormalities for one) and abnormalities in circulating cytokines. It seems that these significant results are contrary, or at least unexplained, by the theory of a hit-and-run infection of the vagus nerve.

    Maybe this explains a subset which has sickness behavior symptoms (fatigue, flu-like symptoms, pain) without immune abnormalities.
  7. alex3619

    alex3619 Senior Member

    Messages:
    6,579
    Likes:
    9,522
    Logan, Queensland, Australia
    The rodent study where the spinal cord was targeted and they measured cytokines and other things is worth reading about. Cytokines were normal in the blood, but not in the spine. This fits with Lipkin's findings, though according to the article this may depend on exactly where on the vagus nerve the infection occurs.

    Every time a new hypothesis or model comes up (and this is an enhancement on older ideas) it might be right. Most hypotheses are probably wrong, being based on incomplete information. In time though one will arise that is correct - is this it? Further studies will tell us. The other point that needs to be considered is subgroups. More than one model may ultimately be proven right.

    In the meantime this raises questions about neuropathy. Do anti-glial drugs work in our neuropathy, as suggested in the article?
  8. alex3619

    alex3619 Senior Member

    Messages:
    6,579
    Likes:
    9,522
    Logan, Queensland, Australia
    Cort explains this in the comments rather well. No cytokines are needed in the blood to invoke a major brain response, only at the vagus nerve. That nerve sends the signal to the brain (probably) that orchestrates the brain response.

    However do be aware that the brain is connected to spinal fluid, and abnormal spinal fluid cytokines may be normal in the blood. Lipkin is looking into this.
  9. SOC

    SOC Moderator and Senior Member

    Messages:
    4,891
    Likes:
    5,361
    USA
    Yes, I think I get that. The thing is, abnormal cytokine patterns are found in the blood in a significant group of CCC/ICC-defined patients, aren't they? Are you thinking that these are somehow getting there from the spinal fluid? Since I don't know much about the immune system, I guess it's not surprising that I don't get how abnormal spinal fluid cytokines can be normal in the blood. :)
  10. alex3619

    alex3619 Senior Member

    Messages:
    6,579
    Likes:
    9,522
    Logan, Queensland, Australia
    Hi @SOC, the article covers this. Whether or not abnormal cytokines are in the blood might (an hypothesis) be due to the location of the infection. If the vagus nerve is infected in the spine then only spinal abnormalities are likely to be found, but if its in the body then it can get into the blood.

    Also the brain response may change our immune system with unpredictable consequences for the most part.

    There is far too much of this model that is still speculative. I wish the science were done tomorrow. Maybe if I wish real hard at New Year?
  11. SOC

    SOC Moderator and Senior Member

    Messages:
    4,891
    Likes:
    5,361
    USA
    Thanks, Alex. I read the article, but I'm really struggling cognitively lately. I appreciate you clearing that up for me. :)

    I'm willing to wish real hard at New Year. :D
    alex3619 likes this.
  12. Ema

    Ema Senior Member

    Messages:
    3,081
    Likes:
    3,085
    Midwest USA
    I'm still confused about the vagus nerve.

    So if it is stimulated, that invokes a parasympathetic response which calms us down in times of stress. This is why they teach the deep breathing exercises to help with stage fright et al - to stimulate the vagus nerve and break the sympathetic fight or flight response and help us focus.

    Yet somehow the vagus nerve is also stimulated when we get a blood draw, which leads to fainting and reduced blood flow to the brain. That doesn't seem useful to helping stage fright.

    I've heard discussion that overstimulation of the vagus nerve is the problem and that drugs like Zofran can calm down an overactive vagus nerve and restore sympathetic/parasympathetic tone.

    But then there is also talk that stimulation of the vagus nerve, like with an implanted stimulator is the way to go possibly for some.

    So which is it - are we trying to stimulate the vagus nerve, calm down the overactive vagus nerve or something else? I don't get it.
  13. lansbergen

    lansbergen Senior Member

    Messages:
    911
    Likes:
    367
    http://www.bioimmersion.com/docs/acth_antiinflam.pdf

    Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice but fails to inhibit
    TNF synthesis in a 7-deficient mice Thus, the nicotinic acetylchlinereceptor a7subunit is essential for
    inhibiting cytokine synthese by the cholinergic anti inflammatory pathway

    http://www.ncbi.nlm.nih.gov/pubmed/21921156

    Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
    Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ.

    Abstract

    Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses.

    .
  14. Ema

    Ema Senior Member

    Messages:
    3,081
    Likes:
    3,085
    Midwest USA
    So this is saying that we want to stimulate the vagus nerve to produce acetylcholine.

    But what if the vagus nerve isn't producing acetylcholine properly anymore because it is overstimulated already? In that case, wouldn't we want to calm it down?

    And how to tell the difference?
  15. lansbergen

    lansbergen Senior Member

    Messages:
    911
    Likes:
    367
    I stimulate the a7nAchR with the immune modulator. That could be the reason I do not have big gut problems. .
  16. katcoff

    katcoff

    Messages:
    13
    Likes:
    1
    The vagus nerve explanation seems very likely to me. I have been sick many decades with CFS, and after investigating the role of the vagus nerve, it could indeed be responsible for some of my symptoms, such as the occasional cardiac arrythmias, IBD, near-fainting spells, as well as the fatigue and flu-like symptoms.
    The hypothesis that there is a chronic herpes infection also makes sense, as I know that shingles is a nerve-base chronic herpes infection which waxes and wanes in intensity like CFS.
    I was tested some years ago for hhv-6 in my blood, but the result was negative, though that's been deemed quite possible as the virus could hide in the nerve tissue and not the blood.
    I read the abstract from VanElzakker. All I can hope for is that his plans to follow up with autopsy-based tissue biopsies or other methods to trace the virus locations are quickly undertaken so that this horrendous condition can be resolved.
  17. alex3619

    alex3619 Senior Member

    Messages:
    6,579
    Likes:
    9,522
    Logan, Queensland, Australia
    Post mortem vagus nerve biopsies are an important step. I wonder if any of our biobanks are prepared for this?
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

    Messages:
    2,641
    Likes:
    2,844
    Cornwall, UK
  19. Fuschia

    Fuschia

    Messages:
    26
    Likes:
    22
    Something I'm trying to understand about this theory if anyone could help me...

    Is it that the infection in the vagus nerve is still present so a low level cytokine response is always humming away in the background, or is it that the initial infection was in the vagus nerve, now gone, but at the time meant that the glial cells were receiving too loud a "virus is present" signal and that that damaged them? Sort of like your eardrums being damaged if you stand next to the loudspeaker.

    In the first case, what is stopping the body simply repressing the virus in the vagus like normal? Is the vagus nerve unusually hard for the immune system to get at? Is it something like the way it's hard for the body to clear a bacterial infection from your sinuses because of low blood supply to the area etc. Maybe it is an infection in the vagus nerve plus an abnormal immune system that leads to me/cfs if the body is having a hard time clearing it.

    If it's the second scenario, could glial damage show up on a scan?
    SOC and voner like this.
  20. Marco

    Marco Old blackguard

    Messages:
    1,130
    Likes:
    714
    Near Cognac, France
    Yes - infections and other 'stressors' can prime and/or activate microglia which can be measured using a PET scan.

    This poster presentation claims to have confirmed microglial activation in ME/CFS which would be A BIG THING :

    http://ras.ni.brain.riken.jp/neuros...keyword=&key_start_disp_num=0&key_disp_num=10

    Unfortunately I've not come across a full published paper.
    SOC, MeSci and Fuschia like this.

See more popular forum discussions.

Share This Page