The Role of Peripheral Nociceptors in Fibromyalgia Syndrome

Prof. Dr. Nurcan Üçeyler, Department of Neurology, University of Würzburg, Germany.

The pathophysiology of pain in fibromyalgia syndrome (FMS) is unknown. Patients mostly describe deeply localized pain in muscles and tendons with high variance in intensity and spatial distribution. Pain mostly starts at circumscribed regions and spreads over the entire body. Patients regularly report of typical additional core symptoms such as sleep disturbance, gastrointestinal problems, subjective cognitive impairment, and depressed mood, which in turn may increase pain. Analgesic treatment is challenging and often leads to side effects rather than being efficient. Hence, most FMS patients stop pharmacological treatment and turn to non-pharmacological therapies with better outcome.
In the last years FMS research has increasingly focused on small nerve fibers (thinly-myelinated A-delta and unmyelinated C fibers), which terminate in the epidermis and mainly conduct pain, thermal sensations, itch, and pleasant touch. Since the first description in 2013, several studies from different laboratories worldwide have been published describing hints for small fiber impairment in FMS patient subgroups. These alterations cover a reduction in fiber quantity as assessed in the skin and the cornea, an increase in small fiber sensory function thresholds, and a reduction in electrical conduction. In parallel, microneurography revealed spontaneously active nociceptors in FMS patients. The underlying mechanisms that lead to small fiber impairment in FMS patients are not understood and it is also unclear, if and how small fiber abnormalities may contribute to FMS pain. Also, these findings are not specific for FMS and do not prove or disprove the diagnosis.
Currently, small fiber assessment does not have a diagnostic impact in FMS patients. Lacking a validated objective biomarker, the diagnosis of FMS is still made following internationally accepted criteria that are based on the clinical presentation and symptom load. However, research on the pattern and underlying pathophysiology of small fiber pathology in FMS has intensified and more studies investigating well characterized large patient cohorts are needed to decipher the underlying pathomechanisms.
In this presentation, current data on small fiber pathology in FMS will be summarized and critically discussed with the audience mainly focusing on methodology, data interpretation, and potential diagnostic and therapeutic implications.