Content area
Full text
Introduction
Fibromyalgia (FM) is a chronic musculoskeletal syndrome, mainly characterized by widespread musculoskeletal pain accompanied by fatigue, neuropathic pain, memory and neurocognitive impairment, chronic fatigue syndrome, joint stiffness, sleep disturbance, emotional distress, restless leg syndrome, depression, mood disorders and dysmenorrhoea (1). It has been documented that dysregulation of pain pathways triggers central sensitization, which increases the sensitivity to pain during FM (2). Thus, allodynia, hyperalgesia and impulsive pain are the clinicopathological features of neuropathic pain due to FM (2). A study estimated that 3–6% of the world population is -affected by FM and that it causes substantial morbidity and disability, predominantly in women (3). Previous studies have suggested that FM significantly affects daily living activities and the health of patients, worsening their quality of life and leading to a loss of productivity (2,4,5). The estimated cost of treatment for FM is between $12-14 billion per year, whereas the mean annual cost per patient is $2,274-9,573, worldwide (6). Thus, FM imposes a significant economic burden on healthcare systems.
Although the exact molecular mechanism responsible for the induction of FM remains to be elucidated, an imbalance in biogenic amines [including 5-hydroxytryptamine (5-HT), norepinephrine (NE) or noradrenaline (NA), and dopamine (DA)] is thought to play an important role in the pathogenesis of central nervous system (CNS) pain during FM (7,8). Clinically, it has been shown that FM is associated with decreased levels of these biogenic amines in the cerebrospinal fluid of patients (9). A previous study noted that DA plays a vital role in pain control (7) whereas, two inhibitory neurotransmitters, NE and 5-HT, are important for the response to harmful stimulation (10). Oxidation of DA and NE in the cytosol causes cellular damage (11). Therefore, various efforts have been taken to ameliorate the pain symptoms in FM via an increase in the activity of neurotransmitters (7). Previous studies have also reported that elevated oxidative stress and an altered antioxidant status are responsible for the induction of FM (12,13). Patients with FM exhibit elevated levels of reactive oxygen species (ROS) in mononuclear cells, suggesting the crucial role of oxidative stress in FM (14). Studies have also reported that alterations in the hypothalamic-pituitary-adrenal axis, central sensitization, muscular dysfunction and alterations in endogenous pain-modulating systems are several other underlying mechanisms...