Looking Ahead to Change: Little by Little
I don't make New Year's Resolutions. I don't think I ever really did, but the last decade or two would have been enough to stifle that impulse. I've just been too aware that I don't have that much control over what happens in my life.
Discuss the article on the Forums.

Ponderings and speculations about purinergic signaling, in pursuit of a unified ME/CFS theory

Discussion in 'General ME/CFS Discussion' started by necessary8, Oct 29, 2017.

  1. Murph

    Murph :)

    Messages:
    507
    Likes:
    2,610
    So (after a quick Youtube tutorial!) I ran a single tailed t-test.

    The difference between female patients and controls delivers a p value of 0.00358.

    Between male patients and controls was 0.02942

    Between all patients and all controls was 0.00183

    That all looks reasonably significant but 450 metabolites were measured and I've selected this one ex-post so we should proceed with caution.
     
    Jesse2233 likes this.
  2. pattismith

    pattismith Senior Member

    Messages:
    650
    Likes:
    908
    some other studies quote some other P2 receptors involved in pain:

    "The review then describes purinergic mechanosensory transduction involved in visceral, cutaneous, and musculoskeletal nociception and on the roles played by receptor subtypes in neuropathic and inflammatory pain. Multiple purinoceptor subtypes are involved in pain pathways both as an initiator and modulator. Activation of homomeric P2X3 receptors contributes to acute nociception and activation of heteromeric P2X2/3 receptors appears to modulate longer-lasting nociceptive sensitivity associated with nerve injury or chronic inflammation. In neuropathic pain activation of P2X4, P2X7, and P2Y12 receptors on microglia may serve to maintain nociceptive sensitivity through complex neural-glial cell interactions and antagonists to these receptors reduce neuropathic pain."
     
    Janice Hargreaves and Hip like this.
  3. Murph

    Murph :)

    Messages:
    507
    Likes:
    2,610
    Thanks @nandixon, your point is supported by what this paper is saying:

    CD39 and CD73 in immunity and inflammation.

    CD39 helps make adenosine which itself is an immunosuppressant. Presumably that is the end phase of the cell danger response, returnign things to normal. The shortage of adenosine but normal levels of eATP could well fit in with Naviaux's theory of a cell danger response that never quite moves through to its last stage.
     
    nandixon likes this.
  4. voner

    voner Senior Member

    Messages:
    541
    Likes:
    846
    View attachment 24907 View attachment 24906
    @dreampop,

    this paper, that I referenced before, cites involvement extracellular ATP signaling & the P2X4 receptor in microglia in the spinal cord in the production of allodynia ,

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489427

    certainly in my body (ME/CFS + FM), PEM includes a dramatic increase in the sensitivity/pain of allodynia....
     

    Attached Files:

    Last edited: Nov 1, 2017
  5. Sidereal

    Sidereal Senior Member

    Messages:
    3,097
    Likes:
    17,174
    Regarding adenosine, I recall Dr Speight (the ME paediatric expert in the UK) anecdotally remarking at one of his talks that some of his recovering patients flipped from the tired-and-wired severe ME presentation to a hypersomnia and extreme sleepiness kind of transition period which could last for a while sometimes before recovery. I wonder if this is the CDR slowly resolving itself, marked by a rise in adenosine. FWIW, I developed the adenosine excess issue a couple of years ago when my condition began to improve substantially. Prior to that, when I was severe, it was pain & insomnia galore.
     
    anne_likes_red, garcia, Hanna and 3 others like this.
  6. PinkPanda

    PinkPanda Senior Member

    Messages:
    206
    Likes:
    542
    Very interesting, thankyou for posting!
    A bit off topic, but what I find interesting are the vitamin B2 and B3 forms, FAD and niacinamide, coming up in the results as low.
     
    Murph, anni66, ljimbo423 and 2 others like this.
  7. lansbergen

    lansbergen Senior Member

    Messages:
    2,505
    Likes:
    2,710
  8. nandixon

    nandixon Senior Member

    Messages:
    824
    Likes:
    2,060
    @bertiedog McClaren is assessing intracellular ATP. In Naviaux’s metabolomics study he's measuring ATP in plasma, which is extracellular.
     
    Hanna and bertiedog like this.
  9. bertiedog

    bertiedog Senior Member

    Messages:
    981
    Likes:
    1,320
    South East England, UK
    Oh thanks for that explanation.

    Pam
     
  10. edawg81

    edawg81 Senior Member

    Messages:
    102
    Likes:
    265
    Upstate, NY
    Before I had a major onset, I had some bizarre ME symptoms (before I even knew I had it). I was very wired and tired for a few weeks, and then one day I magically I started to sleep A LOT, like 12 hours a day (much more than usual for me), I was super foggy, and then after a few days of that, I was normal, no symptoms at all. I was like that until I caught a cold a month later, then I became very symptomatic with MECFS. I know if I ever start to sleep like crazy again, I will go back into remission or some sort of recovery.

    TL;DR: My experience mirrors your experience.
     
    Sidereal and sb4 like this.
  11. wastwater

    wastwater Senior Member

    Messages:
    942
    Likes:
    641
    uk
    Does anyone that wears a wrist watch notice it is sometimes very slack then tight I wonder if there is some kind of swelling going on
     
  12. anni66

    anni66 mum to ME daughter

    Messages:
    214
    Likes:
    832
    scotland
    Yes. My daughter hadvthe ATP pri
    I am not at all scientific, so have probably got this wrong, but does eATP not also activate AMPK via CD39. AMPK via endocrine interaction would seem to be a player in Naviaux's Dauer state as it is involved in CLOCK processes, therefore a CD39 antibody may also affect this pathway?
     
  13. Mel9

    Mel9 Senior Member

    Messages:
    416
    Likes:
    982
    NSW Australia
    Would these proposed mechanisms explain low body temperature after overdoing things physically?
     
    Last edited: Nov 2, 2017
  14. dreampop

    dreampop Senior Member

    Messages:
    207
    Likes:
    506
    If this illness in some part purinergic mediated, would they inflammasone be actived? It is in Fibromyalgia (1) but I could find no studies of it in ME/CFS. Many of the mediators are intracellular, but il-1b and il-18 would be detectable maybe.
     
  15. debored13

    debored13 Senior Member

    Messages:
    348
    Likes:
    163
    Vermont, school in Western MA
    IV ATP would work but would be dangerous. https://www.ncbi.nlm.nih.gov/pubmed/12381087 and related studies...
    messing with the bodies "energy currency" directly is a recipe for disaster
     
  16. necessary8

    necessary8

    Messages:
    67
    Likes:
    253
    @nandixon @Marco @Murph Great finds. I will look over that later.

    I'm crashing right now, so sorry if I don't answer all the questions, I need to rest. I will just say that a lot of your questions are actually answered in my initial post, so you might want to read it again more carefully. (But I unerstand if you can't, brain fog is a bitch)

    I have some good shit planned for part 2, but it will take me a while to write it.
     
    Murph likes this.
  17. Learner1

    Learner1 Professional Patient

    Messages:
    1,105
    Likes:
    1,804
    Pacific Northwest
    My doctor said AMP IVs might be temporarily helpful. He's seen dramatic results with them. He said it's illegal in the US but available in Canada.
     
    pattismith likes this.
  18. debored13

    debored13 Senior Member

    Messages:
    348
    Likes:
    163
    Vermont, school in Western MA
    i'm just saying i've seen two articles so far showing dangerous results from them. look at the research. this isn't the same as feeding the kreb's cycle, directly IVing ATP could be rlly dangerous
     
  19. Learner1

    Learner1 Professional Patient

    Messages:
    1,105
    Likes:
    1,804
    Pacific Northwest
    This is where following random advice from the web may not be the best. I work with 2 excellent doctors who I trust and who are up on all the latest research and are in contact with other experts and who know me and prescribe treatments that are right for me.

    We all need to do what is appropriate for our genes, environmental factors and health status.

    And, with that said, generic studies not done on patients like us may not give accurate info in what works and what doesn't and why.

    You're doing a great job of investigating various concepts ... Keep up the good work! ;)
     
    bertiedog likes this.
  20. debored13

    debored13 Senior Member

    Messages:
    348
    Likes:
    163
    Vermont, school in Western MA
    I guess I'm not saying your doctor is wrong, I'm just saying that IVing ATP carries more risks than supplementing intermediates or cofactors that feed the kreb's cycle. i would assume? that the kreb's cycle has an aspect of being rate limited, so over feeding it with one thing isn't necessarily like the biggest deal, but IV ATP is your bodies energy currency, and taking it directly is ballsy. I guess I'm pointing that out as much for the people here reading as anything... although it would be hard to obtain IV-able ATP anyway... But, like, I would have to trust my doctor with my life to try that, and I hope you do!
     

See more popular forum discussions.

Share This Page