Passive transfer of fibromyalgia symptoms from patients to mice
Goebel A, Krock E, Gentry C, Israel MR, Jurczak A, Urbina CM, Sandor K, Vastani N, Maurer M, Cuhadar U, Sensi S, Nomura Y, Menezes J, Baharpoor A, Brieskorn L, Sandström A, Tour J, Kadetoff D, Haglund L, Kosek E, Bevan S, Svensson CI, Andersson DA. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest. 2021 Jul 1;131(13):e144201. doi: 10.1172/JCI144201. PMID: 34196305; PMCID: PMC8245181.
This is the first research study to suggest that fibromyalgia may be autoimmune! The investigators removed immunoglobulin G antibodies (IgG) from humans with fibromyalgia. They then injected this IgG into mice, and it produced classic fibromyalgia problems in the mice:
– The mice ended up with higher pain levels. In the study, they withdrew paws at lower pressures than normal (using a pain measuring device, a dolorimeter). This meant that the mice felt pain at levels not felt as pain by normal mice.
– Increased cold sensitivity. They removed their paws from a cold metal plate earlier than normal)
– Became less active
– Became weaker (reduced paw grip strength)
– Skin biopsies showed few nerve fibers (like small fiber neuropathy)
– Some IgG from fibromyalgia humans attached to pain nerves in the mice. This provides a clue that there may be specific antibodies that target pain nerves, causing fibromyalgia problems.
– Some IgG from fibromyalgia humans attached to nerves along the spinal cords in the humans. This suggests that there may be antibodies that target nerves in humans, leading to fibromyalgia pain
– However, the IgG from fibromyalgia humans did not produce systemic inflammation. Nor did it produce inflammation-causing cytokines (immune system molecules that allow white blood cells to talk to each other)
– But IgG from “healthy” humans did none of the above!
My initial reactions to this study about fibromyalgia and autoimmune disease:
- Fascinating study!
- It also reminds me of one of my favorite sayings, “The more you know, the more you know you don’t know.”
- Now, if you had asked me 2 years ago if fibromyalgia is due to autoimmunity, I would have said, “No. It is due to overactive pain nerves.” Now, I must question our previous thoughts on fibromyalgia.
- Also, this may be why current treatments for fibromyalgia (exercise and nerve pain medicines) are so crappy. Perhaps we should be using some sort of immune system treatment that can remove these IgG antibodies.
The more you know, the more you know you don’t know.Donald Thomas, MD
What we already know about fibromyalgia and autoimmune disease
– Fibromyalgia is a condition that causes pain in multiple body parts. Fatigue, trouble sleeping, and numerous other problems often accompany this pain.
- Previously, very few doctors or scientists thought that fibromyalgia was due to autoimmunity.
– However, 10% – 30% of autoimmune disease patients (like lupus, Sjogren’s disease, and rheumatoid arthritis) also have fibromyalgia.
– Most fibromyalgia patients respond poorly to the current standard of medical care treatments (exercise, depression therapies, nerve pain medicines, and sleep management).
- Exercising regularly (as in “The Lupus Secrets“) is currently the most effective treatment for fibromyalgia pain.
What this study adds to our knowledge about fibromyalgia and autoimmunity
- We must consider whether fibromyalgia is an autoimmune disease, not simply a “centralized pain syndrome.”
- This is added proof that fibromyalgia is real. Those people (including many healthcare providers, unfortunately) who do not “believe” in fibromyalgia should change their minds and become empathetic and compassionate towards those who suffer from it.
- We may be able to cause fibromyalgia problems by transferring fibromyalgia-causing antibodies from one organism to another.
- Although IgG from fibromyalgia patients may bind to pain nerves and cause fibromyalgia pain, it does this without causing inflammation.
- ………………….. This means that anti-inflammatory, immune treatments may not help. We may need to try immune therapies to remove these causative IgG antibodies. This could explain why anti-inflammatory, immune medicines (like prednisone, methotrexate, and mycophenolate) do not help the fibromyalgia symptoms in patients with autoimmune disorders.
- Click on the link in this sentence to see a nice review article about chronic pain and how it may be due to autoimmunity.
How the study on autoimmunity and fibromyalgia was done (in brief)
- Sweden and the United Kingdom
- Healthy people, fibromyalgia patients, and female mice
- The researchers removed pure IgG from the patients and injected it into the abdominal cavity of female mice.
- They performed numerous tests for pain, cold sensitivity, muscle strength, and activity in the mice.
- In addition, the scientists did not know which mice received IgG from healthy people or fibromyalgia patients (i.e., they were “blinded”).
- They performed skin biopsies on the mice. They studied the skin biopsy pieces under a microscope to count the number of small nerve fibers.
- Immunofluorescence studies of the IgG were done to see if any of it was sticking to the nerves in the mice.
What should be studied in the future about fibromyalgia and autoimmune mechanisms
- Researchers should repeat this study. It would be best to do this in people of different races to see if it is present in diverse groups.
- We should identify the IgG antibodies that bind to the pain nerves and cause fibromyalgia symptoms
- If repeat studies show the above, we should search for treatments that can remove those IgG antibodies. Then, we should test to see if they are safe and reduce or stop fibromyalgia pain. Wouldn’t that be a wonderful thing?!?
Years ago when told I had fibromyalgia in addition to SLE and Sjogren’s, I chose not to have the fibro treated because my understanding was it is not progressive and I was already take so much medication. Does this study confirm that it’s not progressive or shed any light on if it’s safe to continue a non-treatment approach?
Thank you for continuing to educate the autoimmune community. I’ve learned so much from your encyclopedia and blogs.
Ginger: This study does not address whether fibromyalgia is progressive or not. You are correct that although fibromyalgia can be very painful and life-altering (due to fatigue, memory problems, and such), it is not life-threatening. Medical treatments (like duloxetine, amitriptyline, pregabalin, etc.) can have so many side effects that putting up with fibromyalgia and exercising instead of taking more drugs are often preferable. However, it would be wonderful if this science were to lead to effective, safe treatments.
Thanks for the kind words, and comments, and for reading my blog.
Donald Thomas, MD
Thank you for sharing this research. I’ve always thought that it has something to do with autoimmunity, so this is exciting! I’m in my 60’s now, so I may not benefit from the research, but future generations will! It’s so interesting that I first was diagnosed with Lupus, followed by fibromyalgia, then along came inflammatory bowel disease, and most recently RA. I feel that the small nerve neuropathy seen in fibromyalgia is caused by autoimmunity, just no proof, maybe now research will be able to provide proof.
My fibromyalgia has gotten significantly better since I’ve been on Benlysta for SLE, I’m almost pain and fatigue free, and what remains is very manageable and most of the time not disruptive to my daily life.
My experience is that firstly addressing someone else’s comment that fibromyalgia is progressive, provided my8amd those I know with it have all been diagnosed correctly and while doc7may be pretty dismissive of a lot of things regarding my experience, they seem pretty confident in the diagnosis. I would also argue in my experience that regular exercise is the worst treatment for me. It kills me. I’m already wheelchair bound and can’t walk unaided at all. I can’t sit for long in the natural position a chair would have me in because of increased pain and numbness in the legs. Pain medication that is specifically for nerve pain does absolutely nothing for me, and they keep trying to convince me that the type of pain medication that has been working for me doesn’t work for fibromyalgia, despite 10+ years of it helping with pretty steady increases because I know how to take it properly and carefully yet still effectively and no thanks to my drs. I exercise and its immediate effect is instantly worse pain, more severe breathing difficulties and greater weakness and reduced ability to move and increased physical exertion and then a delayed massive spike in fatigue that absolutely floors me and means anything I was still able to do after exercise which wasn’t much, I can no longer do, so if I need the bathroom, a drink, food, it all just has to wait as I cannot lift my arms and can barely keep my eyes consistently open. I’ve tried to explain this but I’m forever met with resistance of how itcannot possibly be that bad as if I don’t know how this has affected me after a lifetime of gradually increasing chronic pain and weird symptoms from childhood until now which takes me to almost 40. It’s greatly frustrating and more so when I continue to be met with accusations of being addicted to my medication also when it’s them constantly trying to throw more pills at things when I go to them and were I addicted I’d be running out long before my prescription is due and I’ve also proved before that I can stop whenever I need to from when they’ve put me on stuff that had me sleeping my life away and they insisted they could do nothing else. They soon found other ways once I’d gone cold turkey and then gone back to them once I’d self-detoxed and was sat in front of them in agony and suffering severely again. Its so difficult because they don’t listen to us and we are the ones suffering.
Raine: thanks for commenting. It is a shame we don’t have better treatments for fibromyalgia. I hope and pray we do sooner than later.
Donald Thomas, MD