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Fibromyalgia: First Proof Found

Fibromyalgia has a reputation as a mysterious illness: The symptoms are diverse, the causes are unknown and the diagnosis is difficult. For the first time, researchers at the University Hospital of Würzburg now have found clear proof of damage to patients' small fibers.

The responsibility for pain and temperature sensation lies with so-called small fibers, i.e. small-caliber pain-transmitting nerve fibers terminating in the skin. In the search for the causes of fibromyalgia-related pain, University of Würzburg researchers have focused their research on these fibers.

With success: "We have detected clear signs of damage to the small fibers in patients with fibromyalgia syndrome," says Nurcan Üçeyler, a private lecturer at the Department of Neurology of the University Hospital of Würzburg. The results of their study are reported in the current issue of the journal Brain.

Paradigm shift: organic basis identified

According to Üçeyler, this discovery heralds a "paradigm shift": The results of the study are highly relevant in that they challenge the conventional pathophysiological concept of fibromyalgia. "Since we have established that the small fibers are impaired in patients with fibromyalgia, the pain related to this disease now fulfils the criteria for being considered as neuropathic pain, i.e. pain arising from an impairment or illness of the nervous system," Üçeyler explains. Furthermore, for the first time, medical professionals have an objectively measurable criterion at their disposal to help them with their diagnosis.

The study

Nurcan Üçeyler and Prof. Claudia Sommer examined 35 patients in their study. 25 of them were affected by fibromyalgia, and ten of them suffered from depression – a condition often ascribed to fibromyalgia patients due to the lack of clear-cut criteria for a reliable diagnosis. The latter ten patients did not experience any pain. In addition, suitable control groups were recruited for each test.

The medical researchers examined the study participants with three specific testing methods: Quantitative sensory testing (QST) is used, among other things, to determine the thermal detection and pain thresholds of the small fibers. The elicitation of pain-related evoked potentials (PREP) provides information on the electrical excitability of the nerve fibers. A punch biopsy provides skin samples for morphological analysis under the microscope. "These three methods are objective procedures, which supplement each other in the assessment of small fiber function, enabling us to make a multidimensional analysis," says Üçeyler.

The results

The study result was clear: "All three test methods revealed definite signs of damage to the small fibers in patients with fibromyalgia syndrome," the medical researcher explains. Fibromyalgia patients were less sensitive to temperature stimuli in the QST test. During the PREP elicitations, those affected by the disease exhibited weaker responses to the pain stimuli. The researchers found significant abnormalities in the microscopic examination as well: "Punch biopsy samples showed a significantly reduced number of small fibers – a finding typical of diseases with small fiber involvement," Nurcan Üçeyler notes.

The researchers found it particularly interesting that fibromyalgia patients not only differed in their test results from healthy study participants, but that they could also be differentiated from patients suffering from depression without any pain symptoms – the latter showed similar results to healthy people. Although fibromyalgia patients had about as many depressive symptoms as the depressive study participants, they were the only ones affected by an impairment of their small fibers.

The team of Nurcan Üçeyler and Claudia Sommer derives a clear result from the study: "Even though it is not yet known why the small fibers are impaired in fibromyalgia patients, our results could provide the basis for a redefinition of the fibromyalgia syndrome as a disease."

The fibromyalgia syndrome

Fibromyalgia affects an estimated two to four percent of the general adult population in western countries. The fibromyalgia syndrome is characterized by chronic pain in several body regions; further symptoms include sleep disturbances, daytime fatigue and depressive symptoms. The disease is more prevalent in women than in men and leads to a greatly reduced quality of life.

The diagnosis is made by excluding alternative diseases on the basis of the patient's description of typical symptoms. Usually, the examination of patients with fibromyalgia reveals no pathological findings, no matter whether clinical tests, laboratory tests or additional apparatus-based diagnostic methods are used. This is why the fibromyalgia syndrome is still not generally recognized as a "real disease" even today: No pathogenic agent or understandable pathological mechanism has been identified for the condition.

Prolonged quest for a diagnosis

Thus, fibromyalgia patients visiting a physician's office are often not taken seriously, having to listen to remarks like: "Fibromyalgia? There is no such thing." They also find themselves frequently confronted with the statement that their complaints are a manifestation of depression. It is true that fibromyalgia patients often also have symptoms of depression. But it's just as possible that these are caused by chronic pain. Due to these "misdiagnoses", it often takes years until fibromyalgia is diagnosed and the symptoms are treated. The long quest for adequate treatment is often frustrating for patients and physicians alike. It also puts a high cost burden on our health system.

The study was financially supported with research funds of the University of Würzburg.

"Small fibers in fibromyalgia syndrome", Nurcan Üçeyler, Daniel Zeller, Ann-Kathrin Kahn, Susanne Kewenig, Sarah Kittel-Schneider, Annina Schmid, Jordi Casanova-Molla, Karlheinz Reiners, Claudia Sommer; doi:10.1093/brain/awt053

Gunnar Bartsch | Uni Würzburg
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