Fibromyalgia: Mechanisms, Current Treatment and Animal Models

Abstract

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by diffuse musculoskeletal pain. In quantitative sensory testing studies, FMS patients display alterations in heat, cold, and mechanical sensitivity. Genetic studies support a key role for the biogenic amine system, and single nucleotide polymorphisms have been identified in serotonin and dopamine transporter and receptor genes of FMS patients. The pathophysiology of fibromyalgia includes contributions from both the ascending and descending somatosensory systems, and decreased central nervous system inhibition of peripheral nociceptive signalling. Three drugs have been approved for the treatment of FMS: Lyrica® (pregablin), Cymbalta® (duloxetine), and Savella® (milnacipran). These drugs were originally developed for indications other than FMS, and were later approved for FMS after successful clinical trials. One hurdle in the development of drugs specifically for FMS is the availability of preclinical animal models of the disease. Recently, several rodent models have been described with potential for translation to the human pain syndrome. In this review, we discuss recent developments toward understanding the pathophysiology of FMS, currently available pharmacologic therapy, ongoing clinical trials, and potential animal models of FMS.

Spinal Cord Stimulation Reduces Mechanical Hyperalgesia and Restores Physical Activity Levels in Animals with Noninflammatory Muscle Pain in a Frequency-Dependent Manner

“…31,33,34,41 For example, in people with fibromyalgia, there is enhanced glutamate in the insular cortex and amygdala, [88][89][90] as well as decreased serotonin and increased substance P in the cerebrospinal fluid. 37,91,92 To mimic these chronic, centrally maintained pain conditions, our laboratory developed a model induced by repeated IM acid injections that mimics the symptoms of chronic muscle pain and has enhanced central excitability with sensitization of dorsal horn neurons, increases in glutamate, and phosphorylation of transcription factors and excitatory neurotransmitter receptors. 59,[93][94][95][96] Furthermore, this model of pain is unrelated to tissue damage, has no nerve injury, and is not maintained by continued primary afferent input from the site of injury.…”

Music reduces pain and increases functional mobility in fibromyalgia

“…Fibromyalgia (FM) is a chronic pain syndrome that is characterized by diffuse multifocal pain accompanied by fatigue, sleep disturbances, depression, cognitive, and memory issues, and alterations in sensory processing such as touch, audition, and vision (Wolfe et al, 1990; Brederson et al, 2011). FM patients also have significant limitations in functional mobility, namely difficulties in goal-directed movements due to generalized musculoskeletal pain (e.g., restrictions in tasks such as rising from a chair and walking), which in turn increase their risk of disability (Jones et al, 2010, 2012; Björnsdóttir et al, 2013).…”

Regulation of Pain in Fibromyalgia by Selective Serotonin and Serotonin Norepinephrine Reuptake Inhibition

“…Even though central nervous system (CNS) desensitization is considered the primary mechanism at the root cause of chronic pain in FMS, evidence of the many co-morbid conditions associated with FMS has strongly suggested that other factors, including genetic abnormalities, some involving biogenic amine dysfunction [18], single nucleotide polymorphisms in the serotonin transporter gene, SCL6A4, and dopamine transporter and receptor genes [19,20]. Altered allelic frequencies between FMS patients and controls were also found in the genes encoding γ-aminobutyric acid A receptor β3 (GABRB3), trace amine-associated receptor-1 (TAAR1) and interferon-induced guanylate-binding protein-1 (GBP1) [21].…”

“…FMS has also been associated with distressful lifestyle [22], hormonal imbalances exemplified by impairment in the hypothalamic/ pituitary/adrenal axis and the growth hormone/insulin-like growth factor-1 paracrine axis [15][16][17][18][19][20][21][22][23], neuroendocrine immunologic dysfunction and defective cell-mediated immunity [24][25][26][27][28][29] all of which may be viewed as contributing to the pathophysiology of FMS.…”