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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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A Neuroinflammatory Model of ME/CFS - Final Part?

Discussion in 'Latest ME/CFS Research' started by Marco, Jul 11, 2013.

  1. Marco

    Marco Old blackguard

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  2. Nielk

    Nielk

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    Thank you, Marco. Excellent comprehensive article full of useful information.
    Have you ever looked into neurofeedback for calming the excoticity of the brain? It has been somewhat useful for me.
     
  3. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Lot of interesting stuff in there, Marco - thanks.
     
  4. Marco

    Marco Old blackguard

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    Thanks Nielk.

    Funny you should mention neuro(bio)feedback.

    I've recently bought a device which aims to balance the autonomic nervous system which I'm trialing over a one month period and will likely write my experiences up for Health Rising.
     
  5. Marco

    Marco Old blackguard

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    Thank you MeSci. Glad you liked it.
     
  6. Firestormm

    Firestormm Guest

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    Thanks Marco. I shall air my thoughts to the wider world as I expressed them to you last night. I am most intrigued by Baclofen for obvious reasons:

    Hope to get back to the substance of your article later today. Thanks for highlighting it here :)
     
  7. Nielk

    Nielk

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    I am looking forward to reading about your experience. I have use the pRoshi system with some benefit.
     
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  8. natasa778

    natasa778 Senior Member

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    Could you post the link or more details on the device please?
     
  9. natasa778

    natasa778 Senior Member

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    Thanks for the article Marco! Wondering if you came across Ibudilast when searching for potential treatments? It is a potent antiinflammatory from Japan, licenced there for few conditions and now in trials for neuropathic pain, opioid withdrawal and chronic migraine. Has some promise for MS ... Migraine trial researchers are expecting glutamate levels to serve as biomarkers

    PS the mechanism behind its expected effects in drug withdrawal symptoms is calming of glial activation
     
  10. Navid

    Navid Senior Member

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    did anyone ever get to try this? if so, any good results?

    thanks,
     
  11. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Baclofen on its own i dont find sedating but when combined with other sleep meds i find it improves the depth and quality of sleep. It has been mentioned in other artilces as the poor mans XYREM which increases deep sleep stage 4 etc. I have also read that tolerance doesnt occur but in my experience it does just like everything else, so i find it good to use intermittently. The highest i have used at once is 75mg, but i find 25mg is enough to help sleep and is the dose i have settled on. I have used it during the day for headaches etc and it has helped but i havent used it alot outside of helping sleep. As for a muscle relaxer i have found its not that good especially with back pain, but thats my experience. Another muscle relaxer tizanadine i have found the same thing, but it does help sleep. For me the best thing i have found for muscle relaxation is lyrica.

    Its good to see these drugs investigated deeper then just their muscle relaxing qualities.

    cheers!!
     
    Marco likes this.
  12. Marco

    Marco Old blackguard

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    Wow!

    Thanks Natasha. That's a new one for me and while I've only skimmed the paper (I'll print it off and read it later) Ibudilast appears to hit all the right targets. Glial cells (astrocytes and microglia) appear to be key to controlling neuroinflammation.

    This caught my eye (bolds added) :



    Based on what I'd outlined in this and previous blogs, I've tried to summarise the model in diagram form :

    Gating diagram.jpg


    Notes :

    A neuroinflammatory cycle may be triggered by a variety of infective, physiological or psychological stressors in individuals with genetic of acquired predispositions.

    Pro-inflammatory cytokines (potentially via attenuated clearance of extracellular glutamate by glial cells) trigger a 'vicious cycle' of neuroinflammation which in itself may be self-perpetuating via 'feed- forward' mechanisms / 'kindling'. The neuroinflammatory cycle depletes antioxidant capacity which feeds back as a perpetuating 'stressor'.

    Neuroinflammtion may result in neural loss in the pre-frontal cortex compromising inhibitory mechanisms resulting in deficits in executive function, attentional mechanisms, working memory, sensory gating and vagal tone which in turn results in a state of autonomic nervous system 'sympathetic dominance'. Neuroinflammation may also result in peripheral and autonomic neuropathies. Together these mechanisms result in increased pain and nociception, fatigue, exercise intolerance, postural hypotension etc. Again these effects feed back as perpetuating stressors.
    Chronic sympathetic dominance is associated with reduced GABA, reduced stress resilience, reduced immune function (which may allow viral persistence) and is essentially a pro-inflammatory state increasing oxidative stress and the production of pro-inflammatory cytokines which in turn further stimulates the neuroinflammatory cycle.

    Persistent sympathetic activity may attenuate the production of protective (against ROS and glutamate excitotoxicity) heat shock proteins (HSPs) – a degenerative deficit also found in ageing.

    This model is potentially self sustaining at the neuroinflammation level and as a global system.
     
  13. Marco

    Marco Old blackguard

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    Interesting. I initially thought the last thing our nervous systems need is additional novel stimuli but they so suggest that it can help break repeating stress related thoughts and re-orient attention. Several studies suggest there are attention orientation problems in ME/CFS.
     
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  14. Marco

    Marco Old blackguard

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    Hi Natasha.

    There may be cheaper alternatives but I hunted around for something with a little science behind it and this site includes some clinical studies (no doubt with some interest in the product) :

    http://stresseraser.com/science-of-the-stresseraser/
     
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  15. vli

    vli

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    Can someone explain to me how glial cell attenuation helps us? I didn't know what glial cells were so I read up on them on wikipedia and I'd think they sounded like something we want more of, not less (which is what I thought attenuation meant?). Thank you!
    PS. I ask because I live in Asia where I can ask my doctor if he can get ibudilast.
     
  16. vli

    vli

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  17. beaverfury

    beaverfury beaverfury

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    Anyone ever tried Ibudilast ? Or any other microglial inhibitors?

    Or Ibuprofen? Wiki - microglia
    Non-steroidal anti-inflammatory drugs (NSAIDs) have proven to be effective in reducing the risk of AD.[17] "Sustained treatment with NSAIDs lowers the risk of AD by 55%, delays disease onset, attenuates symptomatic severity and slows the loss of cognitive abilities. 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'm suspect that ibuprofen caused some of my problems in the first place.
    I was taking it excessively and may have wiped out the mucus lining of my gut in the week i became ill.
    http://www.ncbi.nlm.nih.gov/pubmed/22776871 Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes.

    It also depletes glutathione.

    But maybe if used correctly it may help with neuroinflammation. Just speculation.
     
    MeSci likes this.
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Wow - I didn't know that there actually was evidence that exertion causes gut problems. Thank you for the link - I have saved it. It seems to fit with the leaky-gut model perfectly, including the fact that some or many of us experience an exacerbation of gut problems as part of PEM. I had theorised that it was due to acidosis of the muscles going on to acidify the gut via a reduction of the blood pH, all involving lactic acid. Maybe it is then...

    I am excited about this piece of the jigsaw puzzle! :)
     
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  19. vli

    vli

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    I hv used ibudilast (I'm in asia). it doesn't help me.
     
  20. Marco

    Marco Old blackguard

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    As far as I know ibuprofen (nothing kills a headache like neurofen for me but I only take it occasionally) is a non selective cox-2 inhibitor which explains its adverse effects on the stomach. In contrast celebrex is a selective cox-2 inhibitor that might help tackle neuroinflammation while avoiding the stomach issues.
     
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