Do Fibromyalgia Flares Have a Neurobiological Substrate?

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Introduction

Fibromyalgia (FM) is a chronic central pain sensitivity syndrome manifesting as widespread pain and tenderness with no evidence of soft tissue inflammation [1]. It affects around 2% to 8% of the general population, with a prevalence that increases with age, and marked female predominance [2]. The main clinical manifestations are chronic widespread pain (CWP) with multiple tender points on physical examination, fatigue [3], headaches [4], sleep difficulties, and cognitive disturbances referred to as “fibro fog” [5]. Individuals with FM may also present with nonspecific symptoms of chest, abdominal, or pelvic pain, paresthesias, and lower urinary tract symptoms [6–9]. The 2010 ACR preliminary diagnostic criteria for FM offer nonspecialists a new diagnostic approach that does not require tender point examination and counting, as was the case with the 1990 criteria, and provide a symptom severity scale and a recognition of the importance of cognitive and somatic symptoms in this disorder [10]. Moreover, several functional somatic syndromes (e.g., chronic fatigue syndrome and irritable bowel syndrome), rheumatic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, and ankylosing spondylitis), and psychiatric disorders occur with FM with a frequency that is significantly higher than that of the general population [6,11–15]. Major depressive disorder (MDD) and/or anxiety disorders are found in one-third to one-half of patients at the time of diagnosis [6]. Furthermore, depressed women with FM presented with more severe symptoms, worse overall physical condition, and lower quality of life compared with controls [16]. While the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine and the anticonvulsant pregabalin are both FDA approved as first-line therapies [17,18], nonpharmacological therapies (i.e., aerobic exercises, physical therapy, cognitive behavioral therapy [CBT], and patient education) remain the mainstay of FM treatment [19].