Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia, 2023, Sara Cavaria et al

[Jonathan Edwards]

You have to remember that animal models are always manipulated to just that point where any given influence will make a big difference on the data. Adjuvant arthritis in rats was designed so that almost any intervention would seem to reduce it - same for experimental allergic encephalomyelitis. You can all sorts of effects in these systems that might just about be traceable to some meaningful biology - in that system. But stand back and consider the meaningfulness in terms of a human disease with an unknown aetiology and it is zero.

I have worked alongside people who have made entire careers out of meaningless data in this area. Being critical of basic methodology is considered bad form.

 

[Hutan]

Ha. I wondered whether human neutrophils would work in mice, it seemed a bit amazing. I haven't read the discussion of this paper yet (or much of the Method - which is at the end of the paper. Surely, they will address that issue, it's pretty fundamental.

Well, I didn't see even an acknowledgement of the potential problem of human neutrophils in mice in the paper.

The charts seem to make a good story, but there is a credibility problem.

 

[Trish]

Fascinating discussion, thank you Hutan and Jonathan.
I'm trying to get my head around whether the apparent clear difference shown in the graphs Hutan posted between FM and controls can mean anything clinically for people with FM, or how it could arise if there is no real clinical difference.

 

[FMMM1]

[Jonathan] "stand back and consider the meaningfulness in terms of a human disease with an unknown aetiology and it is zero"

Or less clearly --- if you don't understand the underlying cause, and you simply replicate the symptom (by some means probably unrelated to the actual mechanism in humans) then what is value of the data - likely zero!
Seems to highlight the difficulty in interpreting symptoms and the need for GWAS --- might even get an animal model from that! --- [Jonathan] "Most recent progress in medical research has been in terms of DNA - where the machines do not make many mistakes."

 

[Hutan]

One more thing:

Recent work indicates an immunological basis for fibromyalgia symptoms as passive IgG transfer from patients to mice can confer mechanical pain behavior (48), although we were unable to reproduce these findings (SI Appendix, Fig. S5). This may be due to differences in pain severity (measured through pain VAS) of the patient cohorts that blood samples were derived from and reflects the potential heterogeneity of disease pathogenesis among patients with fibromyalgia.

This study failed to replicate a 2021 study on the transfer of pain behaviour to mice via IgG from people with fibromyalgia. That study made quite a splash at the time.
Forum thread on that study here:
Passive transfer of fibromyalgia symptoms from patients to mice, 2021, Goebel et al

 

[Mij]

A pain expert questioning one of the authors of this paper saying it 'doesn't make sense":

 

[Creekside]

I have little trust in mouse models for pain when no one can clearly define or measure pain. If the mouse doesn't react the way your theory predicts, just change how you interpret observed effects until the results look good.

 

[shak8]

As the saying in the lab goes, "mice lie and monkeys exaggerate." Though I am grateful for any serious attention paid to my illness.

I have no background in the hypothesis and methodology of employing mice in this research topic or any other.

I am merely a human subject with FM who took NSAIDS for three months at the onset of tiny localized patches of pain, just prior to being diagnosed by a rheumy for "probable fibromyalgia."

The NSAIDs for three months did not prevent the ensuing onslaught of severe symptoms of pain, confusion, fatigue and sensitivity to light.

And NSAIDs are ineffective for pain in FM (unless one has co-occuring arthritis). They are not a recommended treatment.