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Passive transfer of fibromyalgia symptoms from patients to mice, 2021, Goebel et al

Discussion in 'Fibromyalgia and Connective Tissue Disorders' started by Andy, Jul 1, 2021.

  1. Andy

    Andy Committee Member (& Outreach when energy allows)

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    Abstract
    Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments.

    Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG.

    Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

    Open access, https://www.jci.org/articles/view/144201


    Guardian article about the study
    "Fibromyalgia may be a condition of the immune system not the brain – study

    "Fibromyalgia – a poorly understood condition that causes widespread pain throughout the body and extreme tiredness – may be caused by be an autoimmune response that increases the activity of pain-sensing nerves throughout the body.

    The findings, published in the Journal of Clinical Investigation, challenge the widely held view that the condition originates in the brain, and could pave the way for more effective treatments for the millions of people affected.

    They could also have implications for patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and “long Covid”. “These different syndromes are symptomatically very similar, so I think it could be very relevant to both of these conditions,” said Dr David Andersson from the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, who led the new study."

    https://www.theguardian.com/society...tion-of-the-immune-system-not-the-brain-study
     
    Last edited by a moderator: Jul 1, 2021
  2. rvallee

    rvallee Senior Member (Voting Rights)

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    Setting aside that anything from KCL is unlikely to be good on this issue, not specifically for these findings, but reading long hauler reports for the last year it's pretty clear that a % of those would normally fall under the fibromyalgia diagnosis without the context of Covid. Very few seem to, though. POTS/dysautonomia and ME/CFS, I've seen plenty. Haven't seen anyone mention being diagnosed with FM even though without this context they would have (eventually anyway, after being told to get lost a few times).

    So to the notion that FM is likely immune, I would say a resounding "DUH", it's frankly obvious. Significant musculoskeletal pain with few other symptoms (but nonetheless still sometimes significant fatigue and brain fog) is a common problem. Seems to affect the legs more than most places, but not exclusively.

    The idea of "central sensitization" was always silly, it would exclude any localization for pain. It's as if people forget how freaking huge our bodies are, when compared to its underlying processes. Lots and lots of places to hide, many of them not accessible to view.
     
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  3. Sid

    Sid Senior Member (Voting Rights)

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    Big if true.
     
    Michelle, Caesar, sebaaa and 14 others like this.
  4. Ariel

    Ariel Senior Member (Voting Rights)

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    What are the ethics standards for mouse studies, if any?
    This made me weirdly sad. (See profile pic) :(

    Edit: sorry about my silly posts sometimes. I just really love animals! :)
     
    Last edited: Jul 1, 2021
    Arvo, Louie41, Michelle and 14 others like this.
  5. Dolphin

    Dolphin Senior Member (Voting Rights)

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    Thread summarising the findings:
     
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  6. shak8

    shak8 Senior Member (Voting Rights)

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    I'll have to reread carefully, but I hope this leads somewhere. Small study. I hope there is expansion on this topic. Exciting!
     
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  7. voner

    voner Senior Member (Voting Rights)

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    @Dolphin, very informative twitter thread, thanks for posting it.

     
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  8. voner

    voner Senior Member (Voting Rights)

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    the "Discussion Section" of the paper ends with this speculation:

    The identification of a pivotal role for autoreactive IgG in the pathophysiology of FMS may transform future research and facilitate development of mechanism-based therapeutic interventions. Our results suggest that therapies which reduce the total IgG titer, such as plasmapheresis or immunoadsorption (e.g., with protein A columns), or which specifically reduce autoreactive IgG (using antigen-specific adsorption) may be effective for FMS (60). Alternatively, symptomatic therapies that interfere with the binding of autoreactive antibodies or pre- vent their functional consequences may also provide effective treatment approaches.
     
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  9. voner

    voner Senior Member (Voting Rights)

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  10. Andy

    Andy Committee Member (& Outreach when energy allows)

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    Louie41, Forestvon, Michelle and 15 others like this.
  11. strategist

    strategist Senior Member (Voting Rights)

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    Very interesting research, and ironic that it comes from King's College psychiatry's department.
     
  12. Hutan

    Hutan Moderator Staff Member

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    To prevent more mice suffering, perhaps those people who have dismissed fibromyalgia as simply the invention of hysterical women would like to volunteer to receive injections of IgG from people with fibromyalgia?
     
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  13. dreampop

    dreampop Senior Member (Voting Rights)

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    Seems very promising. I like that the methods are detailed, so it should be something another group could reproduce. The authors seemed pretty diligent in trying to avoid the possibility of comorbid autoimmune conditions explained in @Andy s video.

    The effect seems to lose steam after 5-6 days.
     
  14. Ravn

    Ravn Senior Member (Voting Rights)

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    :rofl:
    I admit I have speculated about the possibility of giving ME plasma or blood to mice to see what happens but ignorantly assumed that they would probably just die because of cross-species incompatibility. Seems I was wrong and it would be an option. However much I'd rather not hurt any mice. Maybe if Hutan's idea could be adopted :whistle:
     
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  15. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    From the Guardian article:
     
  16. cassava7

    cassava7 Senior Member (Voting Rights)

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    This seems to be a well-conducted study. An encouraging point is that the authors' experiment was successful with blood from both British and Swedish patients, as this study spanned over both countries.

    From the Guardian article:

    Prof Camilla Svensson from the Karolinska Institute in Sweden, who was also involved in the study, said: “Antibodies from people with fibromyalgia living in two different countries, the UK and Sweden, gave similar results, which adds enormous strength to our findings.”
    This study could be of special interest to Dr Scheibenbogen, as her working hypothesis for ME/CFS is autoimmunity. Unfortunately, the unpromising results from her exploratory trials of immunoadsorption, albeit very small, suggest that this finding might not apply to ME/CFS -- or at least that it does not translate directly to it --.
     
  17. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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  18. Sid

    Sid Senior Member (Voting Rights)

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    Wonderful suggestion. I’m sure they’ll volunteer without hesitation seeing as FM is all in the mind.
     
  19. Trish

    Trish Moderator Staff Member

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    Could this be the 'something in the blood' found by several researchers?
     
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  20. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Are there accounts of FM patients who underwent plasmapheresis or immunoadsorption who went into remission?
     

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