Mechanisms of disease: pain in fibromyalgia syndrome. Nature Clin Pract 2:90-98
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
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.
Available from: I.L. Torres
- "Fibromyalgia (FM) is estimated to affect between 1.6%  and 6.4%  of the population, and is characterized by widespread chronic pain accompanied by fatigue, non-satisfying sleep and cognitive symptoms . Although its pathophysiology is not fully understood, abnormalities in pain processing  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  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))  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]. "
[Show abstract] [Hide abstract]
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.
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.
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.
- "The generalized hypersensitivity associated with FMS has focused considerable research interest on central pain modulation mechanisms. Following the establishment of central sensitization, only minimal nociceptive input is required to maintain central sensitization and seemingly non-nociceptive input might also contribute to the maintenance of subsequent pain and mechanical allodynia  . In fact, fibromyalgia pain is consistently felt in deep tissues including ligaments, joints and muscles . "
[Show abstract] [Hide abstract]
ABSTRACT: Muscle fatigue is prevalent in acute and chronic musculoskeletal pain conditions in which myofascial trigger points (MTPs) are involved. The aim of this study was to investigate the association of latent MTPs with muscle fatigue.
Intramuscular electromyographic (EMG) recordings were obtained from latent MTPs and non-MTPs together with surface EMG recordings from the upper trapezius muscles during sustained isometric muscle contractions in 12 healthy subjects.
Normalized root mean square (RMS) EMG amplitude and mean power frequency (MNF) were analyzed. The rate of perceived exertion and pain intensity from MTP side and non-MTP side were recorded.
Pain intensity on the MTP side was significantly higher than the non-MTP side (P < 0.05). Intramuscular EMG from latent MTPs showed an early onset of decrease in MNF and a significant decrease at the end of fatiguing contraction as compared with non-MTPs (P < 0.05). Surface EMG from muscle fibers close to latent MTPs presented with an early onset of the increase in RMS amplitude and the increase was significantly higher than that from non-MTPs at the end of sustained isometric contraction (P < 0.05).
A latent MTP is associated with an accelerated development of muscle fatigue and simultaneously overloading active motor units close to an MTP. Elimination of latent MTPs and inactivation of active MTPs may effectively reduce accelerated muscle fatigue and prevent overload spreading within a muscle.
Available from: Rahimah Zakaria
- "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 . "
[Show abstract] [Hide abstract]
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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.