Mechanisms of disease: pain in fibromyalgia syndrome. Nature Clinical Practice

Evelyn F and William L McKnight Brain Institute and the Division of Rheumatology & Clinical Immunology, Gainesville, 32610, USA.
Nature Clinical Practice Rheumatology (Impact Factor: 5.85). 03/2006; 2(2):90-8. DOI: 10.1038/ncprheum0091
Source: PubMed

ABSTRACT Despite extensive research, the pathogenesis of pain in fibromyalgia syndrome is incompletely understood. Fibromyalgia pain is consistently felt in deep tissues including ligaments, joints and muscles. Increasing evidence points towards these tissues as relevant contributors of nociceptive input that might either initiate or maintain central sensitization, or both. Persistent or intense nociception can lead to transcriptional and translational changes in the spinal cord and brain resulting in central sensitization and pain. This mechanism represents a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal nociceptive input is required for the maintenance of the chronic pain state. Other factors, including pain-related negative affect, have been shown to significantly contribute to clinical fibromyalgia pain. An improved understanding of the mechanisms that characterize central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.

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    • "Fibromyalgia (FM) is estimated to affect between 1.6% [1] and 6.4% [2] of the population, and is characterized by widespread chronic pain accompanied by fatigue, non-satisfying sleep and cognitive symptoms [3]. Although its pathophysiology is not fully understood, abnormalities in pain processing [4] related to central sensitization (CS) and a reduced descending pain modulation with sensory amplification [5,6] have been recognized as components of FM. In the CS model, pain hypersensitivity and enhanced receptive field characteristics of the disease [7] may be explained as a consequence of increased neuronal membrane excitability, synaptic facilitation and nociceptive pathway disinhibition mediated at the molecular level by the modification of receptor kinetics (e.g., N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)) [8] and at the cellular level by the interaction of both neurons and microglia interchanging neurotransmitters and inflammatory cytokines (e.g., substance P, tumor necrosis factor alpha, and brain-derived neurotrophic factor (BDNF)), which results in enhanced neuronal and nociceptive pathway functions [8-10]. "
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    ABSTRACT: Background Fibromyalgia (FM) is conceptualized as a central sensitization (CS) condition, that presents high serum brain-derived neurotrophic factor (BDNF) and neuroglia activation. Although the S100B protein regulates neuroglia functions, it has been traditionally used as a proxy of central nervous system damage. However, neither BDNF nor S100B association with the clinical picture of FM has been elucidated. To explore their association with the pressure-pain threshold (PPT) in FM, we performed a cross-sectional study, including 56 females with confirmed FM aged 18–65 years. Linear regression models were used to adjust for potential confounding factors between serum BDNF, S100B and PPT. Results Serum BDNF and S100B were correlated (Spearman’s Rho = 0.29). Serum BDNF (log) and S100B (log) were correlated with the PPT (log) (Partial η2 = 0.129, P = 0.012 for the BDNF (log), and Partial η2 = 0.105, P = 0.025 for the S100B (log)). Serum BDNF (log) was inversely associated with PPT (log) (β = -1.01, SE = 0.41), age (β = -0.02, SE = 0.15) and obsessive compulsive disorder (β = -0.36, SE = 0.15), while serum S100B (log) was inversely associated with PPT (log) (β = -1.38, SE = 0.50), only. Conclusions Both neuroglia key mediators in the CS process were inversely correlated with the PPT. Serum assessment of BDNF and S100B deserve further study to determine its potential as a proxy for the CS spectrum in FM.
    Molecular Pain 07/2014; 10(1):46. DOI:10.1186/1744-8069-10-46 · 3.65 Impact Factor
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    • "These patients suffer from sleep disturbances, depressive and anxiety symptoms, and impairment of memory and cognitive functions collectively known as “fibrofog” [102-104]. The pathophysiology of fibromyalgia is said to be due to abnormalities of the central pain processing mechanisms that cause central pain sensitization [105-108]. Although few studies have carried out melatonin measurements in patients with fibromyalgia, a single study of 8 fibromyalgia patients showed significantly lower plasma and urinary melatonin (between 23:00 hrs and 07:00 hrs) levels when compared to controls [109]. "
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    ABSTRACT: The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord and supraspinal levels. The mechanism of antinociceptive actions of melatonin involves opioid, benzodiazepine, α(1)- and α(2)-adrenergic, serotonergic and cholinergic receptors. Most importantly however, the involvement of MT(1)/MT(2) melatonergic receptors in the spinal cord has been well documented as an antinociceptive mechanism in a number of animal models of pain perception. Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT(1)/MT(2) melatonin receptors, plays an important role in the pathophysiological mechanism of pain.
    DNA research: an international journal for rapid publication of reports on genes and genomes 06/2012; 10(2):167-78. DOI:10.2174/157015912800604489 · 3.05 Impact Factor
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    • "A recent study targeting active MTPs in FM has shown encouraging results in decreasing spontaneous FM pain and mechanical hyperalgesia in FM [6]. In addition to the peripheral sensitization by active MTPs, central sensitization may also increase MTP sensitivity [16,17] and play a significant role in enhancing peripheral sensitization and normally nonpainful stimuli may be perceived as painful in FM [18]. "
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    ABSTRACT: It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles. A spontaneous pain pattern in FM was recorded in 30 FM patients and 30 healthy subjects served as controls. Local and referred pain patterns induced from active (patients) and latent (controls) MTPs were recorded following manual stimulation. The existence of MTPs was confirmed by intramuscular electromyographical registration of spontaneous electrical activity. Local and referred pain areas induced from key active MTPs in FM were larger than pain areas from latent MTPs in healthy controls (P < 0.001), but were similar to the overall spontaneous FM pain area in FM (P > 0.05). The induced pain area was positively associated with current spontaneous pain intensity in FM (P < 0.01). The locations of key active MTPs in FM patients were found to have latent MTPs in healthy subjects. The muscles containing key active MTPs in FM are often observed in the muscles of extensor digitorum, trapezius, infraspinatus in the upper part of the body and of quadratus lumborum, gluteus medius in the lower part of the body. The overall spontaneous FM pain pattern can be reproduced by mechanical stimulation of active MTPs located in different muscles, suggesting that fibromyalgia pain is largely composed of pain arising from muscle pain and spasm. Targeting active MTPs and related perpetuating factors may be an important strategy in FM pain control. ISRCTN ISRCTN43167547.
    Arthritis research & therapy 03/2011; 13(2):R48. DOI:10.1186/ar3289 · 3.75 Impact Factor
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