Fibromyalgia could be an autoimmune disorder, new research suggests

Mice injected with immunoglobulin G from fibromyalgia patients developed characteristic symptoms of the disease, suggesting the poorly understood disease may be autoimmune, according to a new study.

The mice, like fibromyalgia patients, became highly sensitive to pain and cold, their grip strength diminished as did their range of activity compared with mice injected with IgG from healthy human controls. The research offers new perspective and potential targets for therapy on a disease that has been difficult to treat, researchers note in the Journal of Clinical Investigation.

"It seems we have discovered a previously hidden immune pathology in this disorder, which has long been considered by many people a primary brain problem," Dr. Andreas Goebel, director of the Pain Research Institute at the University of Liverpool, in the U.K., told Reuters Health by email.

"Perhaps our results might prompt a rethink about our approaches to other pain conditions or symptom-based disorders - might autoantibodies play a role here as well?" Dr. Goebel said.

He and a team that included Dr. David Andersson at King's College in London and Camilla Svensson at the Karolinska Institute in Stockholm performed a battery of tests on mice in vivo and in vitro.

They injected the mice with IgG serum from eight fibromyalgia patients and from a group of healthy people, and with serum from fibromyalgia patients that had been stripped of IgG to rule out the possibility that other compounds might be at play.

The team tested pain sensitivity in the mice using two esthesiometers. Point-tipped von Frey filaments press into the paws, and a Randall-Selitto device pinches the paw between a platform underneath and the point of a cone lowered at increasing pressure until the animal withdraws the limb. Cold plates measured cold sensitivity by placing the paws on top and recording the time until the mouse withdraws.

Fatigue and weakness are key symptoms of fibromyalgia, and the mice exposed to fibromyalgia IgG were more lethargic and had reduced grip strength. Remote monitoring showed the test mice covering less ground at night when they are typically active. And a grip strength test found weaker grip in the test mice.

Dr. Goebel and team went on to investigate the pain-receptive nerve fibers of mice that had been injected with the different serums. Sometime after injection, researchers sacrificed the mice and removed skin and attached nerves to study reactions to stimuli.

As expected, the skin-nerve preparations exposed to IgG from fibromyalgia patients was more sensitized to pain and cold. The findings were statistically significant.

Prior research has found abnormalities in peripheral small-nerve fibers in fibromyalgia patients, prompting Dr. Goebel and colleagues to test the effect of IgG on intraepidermal nerve-fiber density. Two weeks after the start of injections with fibromyalgia IgG, nerve fiber density in the hind paw skin had decreased significantly.

A higher dose of fibromyalgia IgG heightened the sensitivity of pain receptors, suggesting potential in therapies that reduce a patient's IgG.

"Possible lines of approach include direct antibody reduction therapies - some of these are already available, immune modulation therapies, and future technologies which will interfere with the yet to be discovered molecular antibody targets or downstream effects," Dr. Goebel says.

Before discovering treatments, however, further research might aim to discover what is different about the IgG in fibromyalgia patients. Identifying biomarkers for fibromyalgia could be an important first step, said Dr. Benjamin Natelson, professor of neurology at the Icahn School of Medicine at Mount Sinai in New York, New York.

The discovery appears to challenge the medical community's understanding of fibromyalgia.

"I've been thinking of it as a brain disease," Dr. Natelson told Reuters Health by phone. "This has been the first paper, for me, that helps understand how something can affect the brain and at the same time the peripheral nerves. I've never really understood what role small-fiber abnormalities have in the genesis of fibromyalgia. This paper doesn't make it clear except that, remarkably, the mice also had changes in the number counts of the small fibers."

But the findings also lend support to a condition that some physicians have considered psychosomatic. Dr. Natelson specializes in the care of patients with myalgic encephalomyelitis, chronic fatigue and fibromyalgia, conditions that are not well understood and that can be downplayed in the medical community. This research legitimizes the disease, said Dr. Natelson, who wrote the book "Your Symptoms Are Real: What to Do When Your Doctor Says Nothing Is Wrong."

—Rob Goodier

This article was originally published on Health News Online Report.