Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
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Anxiety, microglial activation etc

Discussion in 'General Treatment' started by Marco, Nov 22, 2014.

  1. Marco

    Marco Grrrrrrr!

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    Microglial activation/'neuroinflammation' is something of a hot topic in ME/CFS recently and many of us have neuropsychiatric symptoms such as anxiety/depression, cognitive issues etc.

    Typical meds are far from lacking in side effects so it's interesting to find evidence of effectiveness of what appear to be fairly side effect free 'natural' (sic) substances.

    It seems that Luteolin (contained in celery and chamomile for example) seems to be able to dampen down 'neuroinflammation' :

    "We have shown that the flavonoid luteolin is a potent modulator of microglial activation, cell shape, and effector functions. Luteolin induced global changes in the transcriptome of resting or LPS-activated microglia leading to a polarized M2-like phenotype with anti-inflammatory and neuroprotective characteristics."

    http://www.jneuroinflammation.com/content/7/1/3
     
  2. beaverfury

    beaverfury beaverfury

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    Something else to try. Thanks @Marco .

    Minocycline and Japanese knotweed (resveratrol source) definitely helps me in this regard. I have a clearer head and no more pain since taking them.

    Still can't exert myself mentally without payback though. It's like my brain gets swollen.

    If we hang around for another decade someone may fund a mouse study on VanElzakkers vagal nerve theory and go on to develop a tasty microglial inhibitor to put us back into the land of the living.

    I'm glad you investigate all things 'neuroinflammation', Marco. This is my bias regards my personal version of this shitty illness.

    @Ema just posted this. Sinks my heart to think that years of stress beforehand, or 'microglial priming', may have set me up for this illness before a pathogen hit me. (Lyme or virus).
    http://forums.phoenixrising.me/inde...on-causing-immune-problems.33948/#post-526799
     
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  3. Marco

    Marco Grrrrrrr!

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    @beaverfury

    Your version of this illness sounds very much like mine. I'm going through a pretty tough time at the moment with very heightened anxiety and have been trying to get some relief. Beta blockers haven't worked and I've been prescribed a benzo but don't want to go down that route. I had a one off success with a COX-2 inhibitor which cleared the anxiety completely for a few hours but I couldn't repeat the effect. I just bought some chamomile tea for the hell of it.

    Had a tough morning yesterday trying to configure a new modem/router and brewed a cup of the tea. I know we're hyper-sensitive to meds but I didn't expect to get mildly stoned from a herbal tea;)

    So I couldn't help thinking microglia - and lo and behold!
     
  4. adreno

    adreno PR activist

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  5. Marco

    Marco Grrrrrrr!

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    I wonder would stress link to polymorphisms in the P2X7 receptor gene @Simon discusses in this article?

    Triggering Effects: Andrew Lloyd on Infections, Genes and Getting Chronic Fatigue Syndrome

    http://www.cortjohnson.org/blog/2014/11/22/infections-genes-chronic-fatigue-syndrome/

    It seems to be linked to neuropathic pain, and bipolar and major depression with this speculative hypothesis also implicating infection :

    Synaptic P2X7 receptor regenerative-loop hypothesis for depression.

    http://www.ncbi.nlm.nih.gov/pubmed/17558618
     
  6. Marco

    Marco Grrrrrrr!

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  7. beaverfury

    beaverfury beaverfury

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    Excellent links @Marco .

    All the P2X7 stuff is new to me. Thanks for pointing it out. Very interesting article by @Simon on Andrew Lloyd's studies. Surely something useful has to come out of this one day, though what do you do about genetic defects?

    My anxiety is under decent control with Stablon. I also take Magnesium Threonate and Melatonin at night.
     
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  8. Marco

    Marco Grrrrrrr!

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    The PX27 receptor was one of the purinergic receptors that popped up in the Lights' exercise studies and I found this interesting (in an otherwise boring paper) :

    "The purinergic nucleotide receptor P2X7 is increasingly associated with diverse pathological conditions including cancer, pain, inflammation and aberrant responses to infection .........Consistent with its role in amplification of innate immune responses (6-10), genetic association studies link variants of this receptor to the control of Mycobacterium tuberculosis in different populations on three continents"

    Which makes sense in the context of the Dubbo study.

    Good to hear that Stablon is helping. After many attempts to palm me off with antidepressants over the years when I didn't need them I fully expected my Doc to recommend them and I was happy to agree this time. I can't understand why he then suggested a benzo - only to be used when I needed it - when I had explained it was an everyday problem? Unfortunately after a long wait for the appointment I was too mentally trashed to argue.
     
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  9. Thomas

    Thomas Senior Member

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    I'm in the same boat as you folks in the sense that I just can't overuse or strain my brain without suffering what I subjectively call "neuroinflammatory hell" -- that is, the feeling of brain swelling, ears ringing, and very pronounced cognitive exhaustion. I'm already starting to feel the burn from composing this message...

    I may ask my doc to go back on Prozac as it seemed to help with this in the past. And since my relationship with my girlfriend crumbled, I'll be able to deal with the sexual side effects. I am already on Remeron, and low dose Amitryptiline for sleep and IBS.

    As for Benzos, I don't want to recommend something to folks I don't know personally, however, low dose Klonopin has been a life saver for me at times. And I find very low daily doses to be fine and not cause any addiction. It really helps damp down the cognitive overload, especially when in public.

    For very intense things such as my best friend's wedding 2 weeks ago that I promised I would attend. The benzos (and sometimes low dose stimulants) allow me to be present and participate in festivities (albeit it at a much lower threshold and consciousness as my previous fun self).

    I've also been playing around with Reishi mushroom extract as I belive in large doses it can be a potent microglial dampener.

    Lastly, as for stress. Yes, not a day goes by that I don't think that if perhaps if I were less stressed throughout my life, had I been able to avoid this damn mess of ME. Who knows. That's the toughest pill to swallow for sure! (pun intended)
     
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  10. Marco

    Marco Grrrrrrr!

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    Bingo with the first paragraph Thomas (and everything else for that matter).

    I'm pretty sure that there's a stress related ME/CFS that needs to be slotted in to @Jonathan Edwards proposed collection of 'ME's.

    Thanks for the reassurance also on benzos. I'm still a little concerned about neurological kindling if using occasionally.
     
  11. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am prepared to believe that stress is a factor. I just worry that it is an easy way of 'explaining away'. And at least for adolescents 'unstressing' seems to make no difference - a fully supportive environment can get nowhere. It seems a bit of a blind alley for research ideas. On the other hand if there is an 'ME3' limbic/cingulate/endorphine loop that stress can feed in to as well as viruses/cytokines/antibodies maybe neuropharmacologic clues like naltrexone are pointing in the right direction?
     
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  12. Marco

    Marco Grrrrrrr!

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    It certainly wasn't my intention to 'explain things away'. From what I've gathered 'stress' whether psychological or in the original sense as proposed by Selye is just as potent a 'stressor' on the immune system as infection and does tend to be chronic.
     
  13. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Sure, I am not suggesting you are explaining away, Marco. I just worry that others use the term stress in a hand-waving sense to do that and send everybody off for CBT without thinking further. I guess that it is a slippery concept unless one focuses in on the biochemical pathways - like microglial activation mechanisms.
     
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  14. SDSue

    SDSue Southeast

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    Well said. Because many (most?) of us have been dismissed as "anxious" or "stressed" by doctors, family, friends, etc, this is a touchy subject, indeed. I appreciate those who look beyond any stressors to acknowledge the underlying mechanisms and pathways.
    I wonder this myself. Immediately prior to falling so ill, I was under enormous stress for an extended period of time. I've always thought the unrelenting stress made me vulnerable to ME/CFS, and that is a tough pill to swallow.
    Ditto! It's not a "headache" in the typical sense.
     
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  15. beaverfury

    beaverfury beaverfury

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    It would be nice if we knew what the precise aim of 'inhibiting' microglia was, regards ME/CFS. Obviously we want them working optimally rather than just shut down, which they don't seem to be doing in a range of diseases.

    Until then I'm happy to pour chemicals on them that seem to shut them up.

    Ibuprofen might be one.
    'The main cellular target for NSAIDs is thought to be microglia. This is supported by the fact that in patients taking NSAIDs the number of activated microglia is decreased by 65%."[17]

    I wonder if the Celebrex in Dr Pridgen's antiviral trial is adding benefit through microglial inhibition?

    'Studies have shown that long-term neuroimmune activation persists after the herpes infection in patients.[23] Microglia produce cytokines that are toxic to neurons; this may be a mechanism underlying HSV-related CNS damage.[23] It has been found that "active microglial cells in HSV encephalitis patients do persist for more than 12 months after antiviral treatment."[23] http://en.wikipedia.org/wiki/Microglia
     
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  16. Marco

    Marco Grrrrrrr!

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    This is true of course when there is a evidence gap that allows for baseless theories and 'pragmatic rehabilitation'.

    On the other hand - and I fully appreciate why, I fear we have become overly defensive and reluctatnt to discuss symptoms that many of us experience and which might be a significant component or even represent a distinct sub-group.

    Examples abound of 'mood' and neuropsychiatric symptoms associated with neurological, metabolic and even autoimmune diseases which do not appear to result from living with a chronic illness and I'm sure few would now claim a psychological or stress related basis for primary Sjogren's for example. Where incidentally elevated rates of anxiety/depresssion may be correlated with this P2X7 receptor :

    The expression of P2X7 receptors on peripheral blood mononuclear cells in patients with primary Sjögren's syndrome and its correlation with anxiety and depression.

    http://www.unboundmedicine.com/medl..._its_correlation_with_anxiety_and_depression_
     
  17. Little Bluestem

    Little Bluestem All Good Things Must Come to an End

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    But might not a fully supportive environment allow other treatments to be more effective?
     
  18. BurnA

    BurnA Senior Member

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    Is there any evidence that stress can cause disease ?
    My opinion is stress, virus', and psychological issues are the three cards some doctors like to play when they haven't a clue whats going on.
    The problem with stress is that most people are under some form of stress so if they are asked they might tend to agree that they were 'under stress' but is general everyday stress likely to cause disease ?
     
  19. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I tend to agree. But we may be wrong.
     
  20. Marco

    Marco Grrrrrrr!

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    There are certainly lots of claims of an association although it would take a systematic review to sort out an real effects if any. But there does appear to be some evidence that psychological stress activates the same immune pathways in the brain as pathogens and tissue damage.
     

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