Article

Fibromyalgia: From pathophysiology to therapy

Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, 48106, USA. tobiass@ med.umich.edu
Nature Reviews Rheumatology (Impact Factor: 10.25). 07/2011; 7(9):518-27. DOI: 10.1038/nrrheum.2011.98
Source: PubMed

ABSTRACT Individuals with fibromyalgia generally experience chronic widespread pain, which can be accompanied by further symptoms including fatigue, sleep disturbances, cognitive dysfunction, anxiety and depressive episodes. As the recognition and diagnosis of fibromyalgia has improved, the availability of therapeutic options for patients has increased. Furthermore, research into the neurobiological mechanisms that contribute to the chronic pain and concomitant symptoms experienced by patients with fibromyalgia has advanced our understanding of this debilitating disorder. In this Review, we aim to provide an overview of existing pathophysiological concepts. The roles of biological and psychological stress, genetic factors, and pain and sensory processing in the pathophysiology of fibromyalgia and related conditions are discussed. In addition, pharmacological treatments, including monoamine modulators, calcium channel modulators and γ-aminobutyric acid modulators, as well as nonpharmacological treatment options are considered.

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    • "Neuropharmacology nociception transmission, as the patients experience reduced pain threshold with exaggerated pain sensation, likely dependent on central sensitization (Gracely et al., 2002; Jensen et al., 2012; Petersel et al., 2011; Smith et al., 2011; Staud, 2012). These sensorial alterations are linked to diminished levels of monoamines, and increased production of excitatory neurotransmitters throughout brain (Harris, 2010; Schmidt-Wilcke and Clauw, 2011). Furthermore , some studies point out the relevance of inflammatory pathways in the pathogenesis of fibromyalgia, considering that cytokines are implicated in both induction and maintenance of pain (Kadetoff et al., 2012; Üçeyler et al., 2011, 2006). "
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    ABSTRACT: This study investigated whether the spinal or systemic treatment with the lipid resolution mediators resolvin D1 (RvD1), aspirin-triggered resolvin D1 (AT-RvD1) and resolvin D2 (RvD2) might interfere with behavioral and neurochemical changes in the mouse fibromyalgia-like model induced by reserpine. Acute administration of AT-RvD1 and RvD2 produced a significant inhibition of mechanical allodynia and thermal sensitization in reserpine-treated mice, whereas RvD1 was devoid of effects. A similar antinociceptive effect was obtained by acutely treating animals with the reference drug pregabalin. Noteworthy, the repeated administration of AT-RvD1 and RvD2 also prevented the depressive-like behavior in reserpine-treated animals, according to assessment of immobility time, although the chronic administration of pregabalin failed to affect this parameter. The induction of fibromyalgia by reserpine triggered a marked decrease of dopamine and serotonin (5-HT) levels, as examined in total brain, spinal cord, cortex and thalamus. Reserpine also elicited a reduction of glutamate levels in total brain, and a significant increase in the spinal cord and thalamus. Chronic treatment with RvD2 prevented 5-HT reduction in total brain, and reversed the glutamate increases in total brain and spinal cord. Otherwise, AT-RvD1 led to a recovery of dopamine levels in cortex, and 5-HT in thalamus, whilst it diminished brain glutamate contents. Concerning pregabalin, this drug prevented dopamine reduction in total brain, and inhibited glutamate increase in brain and spinal cord of reserpine-treated animals. Our data provide novel evidence, showing the ability of D-series resolvins AT-RvD1, and mainly RvD2, in reducing painful and depressive symptoms allied to fibromyalgia in mice.
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    • "This present review updates knowledge on the involvement of endocrine axes and peripheral nervous systems in chronic inflammatory diseases (CIDs). We do not touch non-inflammatory fibromyalgia or stress-related aspects of rheumatic diseases because these subjects are demonstrated elsewhere in extensive form [2] [3]. Since the 1990s, knowledge increase in the field of neuroendocrine immunology of the rheumatic diseases entered an exponential phase. "
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