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STUDY: Miserable mice! Fibromyalgia transplanted to mice…in blood?

 •  • by Paul Ingraham
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Fibromyalgia is the unexplained disease of widespread pain and fatigue — symptoms that have now been diabolically “transplanted” from humans to mice, in a new experiment (see Goebel et al).

The effect was temporary, thankfully, but for a couple weeks after mice are injected with serum from people with fibromyalgia, they seem to be struck down by fibromyalgia themselves. They get sluggish and weak. They flinch away more dramatically from cold and pressure. Nerves in their skin actually shrivel up (I am not kidding). These signs are all familiar to us from human fibromyalgia.

How is fibromyalgia making the leap to the mice? Goebel et al. had something in mind, because there are many clues that fibromyalgia involves the immune system in some way. The bearer of the bad news appears to be one our most common antibodies, the immunoglobulin G (IgG), an immune system workhorse. The mice were safe when IgG was filtered out of the serum or when the serum came from healthy humans. Only serum with “bad IgG” from fibromyalgia patients was a threat to the mice.

The mice bounced back as levels of human IgG levels in their little systems slowly declined over a few weeks. Phew! I accept that mice are essential in medical research. Doesn’t mean I have to like it.

The Monument to the laboratory mouse is a sculpture in Novosibirsk, Russia, commemorating the sacrifice of the mice in genetic research. Photo by Irina Gelbukh (cropped, CC BY-SA 3.0

What is immunoglobulin G?

Immunoglobulins (Ig) are antibodies, molecules that identify and neutralize invaders, and G is one major class of them, a family of proteins with many properties that distinguish it from other major types. For instance, it’s the only type of antibody that crosses the placental barrier, so it has a crucial role in infant immunity. It’s also strongly associated with allergic responses, including anaphylactic shock.

One key thing to note is that we can’t just get rid of IgG. It’s too important.

And what’s wrong with it in fibromyalgia?

As with all things immune, IgG is just stupidly complex, and it’s more of a family of proteins than “a molecule.” There are many ways that IgG — as a class of antibodies — can be different in fibromyalgia patients.

Just knowing that fibromyalgia patients have “bad IgG” isn’t super helpful, because we don’t know why or how it’s bad — and you can’t just get rid of it. Goebel et al. suggests that therapies that reduce our total IgG supply somewhat “may be effective,” but we have no idea. Blocking their effects is another promising approach, but complicated. All of this will take a lot of work. Still, at least it’s a promising place to look.

(And there are probably several sub-types of fibromyalgia, and they probably don’t all involve tainted rogue IgG.)

Flaws and limitations?

I am not qualified to find specific fault in this quite technical study, but I didn’t pick up on any red flags. Of course it’s “just an animal study,” and we know that “mice lie and monkeys exaggerate,” the biologist’s lament about the unreliability of animal models. Different species can be weirdly impervious to things that are nasty for others.

But this is a bit different from the usual “we learned something about how animals work, but we have no idea if humans are the same.” When a well-described disease in humans can be inflicted on mice with an extremely specific procedure, there’s a good chance it’s an important finding — even if we’re not sure what to do with it yet.

This paper has now been added to the PainSci fibromyalgia guide in a new section, “Useless but fascinating: the greatest hits of fibromyalgia research.”

A Rational Guide to Fibromyalgia — The science of the mysterious disease of pain, exhaustion, and mental fog. (22,000 words, 89-min read)

Goebel A, Krock E, Gentry C, et al. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest. 2021 Jul;131(13). PubMed #34196305 ❐ PainSci #52110 ❐