The Evidence: Fibromyalgia may be an autoimmune condition

In a paradigm shifting new study, researchers were able to trigger fibromyalgia symptoms in healthy mice by injecting them with blood from fibromyalgia patients. Specifically, scientists injected the mice with IgG antibodies from individuals with fibromyalgia in England and Sweden.

IgG antibodies (immunoglobulin G) are immune proteins that attach to foreign substances so the immune system can neutralize them. IgG antibodies recognize and target pathogens and toxins. Sometimes rogue IgGs, called autoantibodies, turn against our own bodies, and are directed against our own tissues, like joints or organs, which is what characterizes autoimmune disorders.

When IgG antibodies from fibromyalgia patients were injected into healthy mice, the mice developed fibromyalgia-like symptoms, such as an increased reaction to pain, less physical activity, and reduced muscular strength. After two weeks, once the IgG injections wore off, the fibromyalgia symptoms experienced by the mice reversed. In contrast, IgG injections from healthy people into mice did not cause any symptoms. Importantly, injecting mice with blood from fibromyalgia patients that had been filtered free of IgG antibodies also had no effect on pain sensitivity in the mice.

From these results, the researchers concluded that “fibromyalgia pain is caused by IgG autoantibodies,” and is likely an autoimmune condition. This is a profound change in how we understand and treat fibromyalgia.

But how do IgG antibodies trigger fibromyalgia pain?

 The answer lies in where fibromyalgia IgGs appeared to target their activity in the body – the nervous system. Researchers examined tissues from the mice that had been injected, and detected fibromyalgia IgGs in specific nervous system cells that affect sensory nerves. In order to understand these findings, let’s define a few areas of the body:

Sensory neurons are nerve cells that carry information about sensations, like temperature, pressure, or pain.

Glial cells support, protect and take care of nerve cells by providing structural support, insulation, and nutrients, as well as modifying nerve signaling.

A dorsal root ganglion is a cluster of neurons around the root of a spinal nerve, just outside of the spinal cord. The cluster includes sensory neurons carrying information from the body to the spinal cord. Glial cells in the cluster form a layer around the cell bodies of these sensory neurons.

In this study, the researchers primarily discovered fibromyalgia IgG antibodies in glial cells of the dorsal root ganglia (the support cells in the cluster of sensory neruon cell bodies).

This finding means that fibromyalgia IgGs target glial cells that support and regulate sensory nerves, sensitizing them to pain signals. In other words, the immune system has gone haywire, and IgG antibodies are being directed against sensory nerve structures carrying pain signals. Hyperactive sensory nerves send more intense and frequent signals communicating the presence of pain.

But this isn’t the first time a discovery like this has been made. “Autoimmune pain” is a new term that describes how specific IgG antibodies can target different nerve structures, causing sensory nerves to become hyper-sensitive to pain and other sensations. But autoimmune pain has never previously been linked to fibromyalgia.

Putting this all together, fibromyalgia may be an autoimmune condition in which specific IgG antibodies target glial cells in dorsal root ganglia, causing the sensory neurons supported by the glial cells to become hypersensitive to pain.

How will this discovery change future research and treatments for fibromyalgia?

As a disorder of the immune system, a number of new treatments will open up for fibromyalgia that have previously been used for other autoimmune conditions. As we saw in the mouse study, the depletion of fibromyalgia IgG antibodies (once the human IgG injection stopped) reversed fibromyalgia symptoms. Theoretically, treatments currently used for autoimmune conditions like myasthenia gravis, which filter out the amount of IgG antibodies circulating in your bloodstream, could reduce fibromyalgia symptoms! “Plasma exchange is a dialysis-like procedure that is performed on a patient’s vein. An individual is hooked up to a machine that nearly simultaneously removes the blood and puts it back in. The machine “skims” the blood of harmful antibodies. Removing the antibodies prevents them from causing muscle weakness.”

 It’s important to remember that this study was conducted on mice, not humans, so much more needs to be done before we can understand or treat fibromyalgia as an autoimmune condition.

Autoimmune pain explains why fibromyalgia is a pain condition without inflammation, because the immune system (IgGs) directly targets the nervous system. The absence of inflammation, a hallmark of most injuries, and pain conditions like arthritis, has historically been used to suggest fibromyalgia is “all in your head” or “psychosomatic.” Studies like this one will hopefully be the nail in the coffin of the doubts about the physical pathology of fibromyalgia – it’s “all in the body!”

Critically, no fibromyalgia IgG was discovered in the brain or spinal cord (brain and spinal cord)  tissues of the affected mice, demonstrating that the fibromyalgia pain was caused by the sensitization of sensory neurons in the body.

Previous research has shown substantial alterations in central nervous system activity in people with fibromyalgia compared with healthy individuals. The researchers suggested that the hyper-sensitization of sensory nerves in the dorsal root ganglia, which are located just outside of the spinal cord, could alter nervous system activity in the spinal cord, thereby causing the patterns of central nervous system characteristic of fibromyalgia. However, further research needs to clarify the body vs. brain debate over the mechanisms of fibromyalgia pain processing dysfunction.

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.