Fibromyalgia is characterized by widespread, mainly muscular pain that is exacerbated during and following physical activity. Although mechanisms such as muscle ischemia and peripheral nerve fibre pathology have been implicated in fibromyalgia, currently no known peripheral pathology can fully account for the pain. Therefore, the pain in fibromyalgia is most likely explained by a complex interaction between peripheral and central mechanisms. Fibromyalgia patients are characterized by a multimodal, widespread, increase in pain sensitivity and a dysfunction of endogenous pain inhibitory mechanisms. Imaging studies have revealed functional as well as structural cerebral abnormalities in fibromyalgia. During painful stimulation, fibromyalgia patients exhibited an inability to activate cerebral structures associated with the descending pain inhibitory system, i.e., rostral anterior cingulate (rACC) and thalamus1. There was no association between depression or anxiety and cerebral processing of evoked pain, indicating segregated mechanisms for mood and pain processing2. Furthermore, FM patients had less pain related functional connectivity within the brain's pain inhibitory network and structural changes such as decreased cortical thickness and reduced brain volumes3. Longer duration of FM pain was associated with more pronounced functional and structural abnormalities suggesting a time-dependent progress of cerebral pathology, even when controlled for age and mood3. In addition, FM patients had elevated interleukin-8 in the cerebrospinal fluid indicating neuro-inflammation4, possibly due to glia cell activation. Interleukin (IL)-8 is co-localized with translocator protein (TSPO) in glia cells. During glia activation, the production of TSPO is increased and TSPO agonists are involved in the regulation of the expression of IL-8 and it's receptor, thus affecting glia to neuron signalling and central sensitisation. We have recently documented that FM patients who are carriers of the genetic functional polymorphism associated with high TSPO binding affinity report higher pain intensity and more severe fibromyalgia symptoms compared to genetically inferred TSPO low affinity binders and that this genetic polymorphism also affects cerebral pain processing5. To our knowledge, this is the first finding of genetic mechanisms associated with symptom severity in FM.
Finally, the effect of different treatments on central pathology in FM will be discussed. Short pain duration was predictive of a positive response to a 12 weeks treatment with a serotonin-noradrenalin re-uptake inhibitor (SNRI)6. The degree of symptom improvement and reduced pain sensitivity in SNRI treated FM patients corresponded to the degree of increased pain related activation of cerebral areas associated with pain modulation and the default mode network6. In contrast, cognitive behaviour therapy did not affect clinical pain or pain sensitivity but increased activations of cerebral regions implicated in executive cognitive control during painful stimulation and thus likely reappraisal of painful stimuli7. Finally, 15 weeks of physical exercise partially normalized resting state activity in FM8. The results demonstrated that different treatment modalities affected specific brain mechanisms, indicating that at least some of the cerebral abnormalities in FM are reversible.
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Disclosure of Interest None declared