Has the cause of fibromyalgia finally been unraveled?

Researchers at Ghent University have found a new explanation for the chronic pain syndrome fibromyalgia and are paving the way for new treatments.

Fibromyalgia affects up to an estimated 5 percent of the European population. This chronic condition is accompanied by persistent pain in the muscles, joints, tendons, ligaments and organs that cannot be explained by demonstrable tissue damage. In addition, many patients suffer from chronic fatigue, sleep apnea, bladder and bowel problems, anxiety and sleep disorders, and heart and blood pressure problems. And there is no clear reason for these additional complaints either.

Until now, scientists have been in the dark about the cause of this chronic pain syndrome and there is also no treatment that can cure fibromyalgia. Researchers Boel De Paepe, Joél Smet, Chris Baeken, Jessica Van Oosterwijck and Mira Meeus from Ghent University believe that they have partially solved the mystery and that their findings could form the basis for new therapies that can cure fibromyalgia.

Imbalance in brain area

The researchers analyzed the existing literature on the disease and were able to put together a number of crucial pieces of the puzzle that could explain what exactly fibromyalgia is and what can be done about it.  

“Our starting point was that many people who suffer from chronic pain for which no clear cause can be found, also very often suffer from other recurring disorders,” says Dr. Boel De Paepe. She is a scientist affiliated with the Neuromuscular Reference Center of UZ Gent and lead author of the study. For example, patients often complain that they have palpitations or are out of breath, even though they have not been exerting themselves. Due to this complex complaint pattern, these patients are often followed by doctors with different medical specializations. We wanted to find out what the common factor was between all those associated complaints, which you would initially think are very different in nature. ‘

When the researchers put the pain and all the other syndromes together, one brain area clearly emerged as one of the key regions that could explain all those different symptoms. And that was the insula, a brain area that processes pain stimuli and controls processes of the autonomic nervous system that regulate, among other things, heart rate, digestion and intestinal peristalsis.

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In their search of the existing literature, they found a study showing that a reduced density of the thin nerve fibers could be demonstrated in about 60 percent of patients with fibromyalgia. This finding was initially reminiscent of thin fiber neuropathy, a condition that leads to pain complaints in the hands and feet and seems to explain the cause of fibromyalgia in physical processes. But another study in which experiments in rats increased the level of the neurotransmitter glutamate in their insula found that the animals not only became more sensitive to pain, but also that the thin nerve fibers in their hind legs became less dense. In other words, that reduced nerve density was most likely caused by an imbalance in the insula.

The researchers put all those puzzle pieces together and propose that there is an imbalance in the insula of fibromyalgia patients between the stimulating neuro-transmitter glutamate on the one hand and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) on the other. According to them, this imbalance of neurotransmitters in the insula disrupts the central nervous system and is not only at the basis of the chronic pain in fibromyalgia, but also of all other complaints associated with the disease. 

They do not yet know exactly what causes this imbalance. They suspect that there may be a genetic predisposition and that environmental factors such as stress may be a trigger that causes the disease. ‘Very often patients with fibromyalgia can clearly indicate when their symptoms started,’ says Dr. De Paepe. ‘Very often there was a trigger, such as a serious illness or a major event in their lives. We suspect that there is an underlying genetic predisposition to fibromyalgia and that the disease only emerges in stressful situations. ‘

That fibromyalgia used to be dismissed as a disease of women in their 40s is now completely outdated. “Most patients are still women, but men can also suffer from fibromyalgia,” says Dr. De Paepe. In addition, the age at which people complain of chronic pain that cannot be explained is very variable. Even children are not spared it. ‘

Importance not to be underestimated

The importance of these new insights can hardly be underestimated. Interestingly, the diagnosis of fibromyalgia can be objectively diagnosed in up to 60 percent of patients by looking for damage to the small peripheral nerves. This can be done by taking a skin biopsy, but also by determining the fiber density in the cornea using a technique called corneal confocal microscopy. 

The fact that the disease can be medically proven is very important for patients because it proves that the disease is not in their heads, but has a demonstrable neurological cause. “Until now, fibromyalgia has been diagnosed by ruling out other things,” says Dr. De Paepe. ‘If there is nothing wrong with the muscles in which you have pain, it may be fibromyalgia. As a result, patients often have the feeling that something is being missed, while pain is a strong signal from the body that something is going wrong. ‘  

In addition, the findings could lead to new treatments for fibromyalgia. Until now, patients have only been dependent on physiotherapy, sleep advice and cognitive behavioral therapy to deal better with their complaints, but these cannot cure the disease. The insula may be the target for new therapies that can make fibromyalgia disappear for good. ‘There are indications that electromagnetic stimulation can normalize the functioning of the insula and is more targeted than medication’

There is not yet a recognized effective treatment that can cure fibromyalgia, but medications that act on the neurotransmitters already exist, and more neuromodulating agents are in the pipeline. “For fibromyalgia, they could restore the balance between glutamate and GABA, either by decreasing glutamate by blocking its receptors or by giving GABA analogues to artificially raise the level of gamma-aminobutyric acid,” says Dr. De Paepe . ‘The disadvantage of this is that medication for pain relief often works systemically and has effects on the whole body, which can cause unpleasant side effects. More selective medication and techniques can avoid this, for example by locally stimulating the insula itself electromagnetically. That is still experimental for the time being,

Phantom pain

Dr. Finally, De Paepe points out the similarities between fibromyalgia and phantom pain. ‘In the past, patients with an amputated arm who complained of pain in their arm were told that they could not experience pain because they no longer had that arm. Now phantom pain has been recognized as a definite pain syndrome. As with people with phantom pain, fibromyalgia patients’ body’s pain processing mechanism no longer functions as it should, so they continue to experience pain long after the cause of that pain has disappeared. Scientists try to unravel and restore that mechanism. ‘

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