Fibromyalgia - Pathology

Central Nervous System - updated: 14 September 2009

Fibromyalgia: present to future

Curr Rheumatol Rep. 2005 Oct;7(5):371-6

Bennett R.

There has been a dramatic increase in our understanding of fibromyalgia throughout the past 14 years since the publication of the 1990 American College of Rheumatology classification criteria. Before 1990, and for most of the 20th century, fibromyalgia was considered to be predominantly a muscle disorder; now the critical abnormality is described as "central sensitization." However, central sensitization has to have an initial genesis and nociceptive stimuli from painful foci in muscle are increasingly recognized as being relevant to the development of fibromyalgia. Clinicians also recognize an association between the initiation of fibromyalgia and chronic psychologic stressors and inflammatory disorders. It has been more difficult to understand how two such apparently diverse events could affect central pain physiology. However, some clues are emerging from the role of diverse stimuli in activating glial cells and the role of disordered cytokine networks. Some predictions about future developments in fibromyalgia are ventured based on the current state of knowledge.

Publication Types:

• Review

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment

Curr Pharm Des. 2008;14(13):1274-94

Gur A, Oktayoglu P.

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis. Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin. Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function. To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

Publication Types:

• Review

Neuroendocrine mechanisms in fibromyalgia-chronic fatigue

Best Pract Res Clin Rheumatol. 2001 Dec;15(5):747-58

Buskila D, Press J.

Fibromyalgia and chronic fatigue syndrome are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction. This chapter presents data demonstrating neurohormonal abnormalities, abnormal pain processing and autonomic nervous system dysfunction in fibromyalgia and chronic fatigue syndrome. The possible contribution of the central nervous system dysfunction to the development and symptomatology of these conditions is discussed. The chapter concludes by reviewing the effect of current treatments and emerging therapeutic modalities in fibromyalgia and chronic fatigue syndrome. Copyright 2001 Harcourt Publishers Ltd.

Publication Types:

• Review

Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia

CNS Spectr. 2008 Mar;13(3 Suppl 5):12-7

Staud R, Spaeth M.

Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent 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 peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes

Publication Types:

• Review

Proton MR spectroscopy in the evaluation of cerebral metabolism in patients with fibromyalgia: comparison with healthy controls and correlation with symptom severity

AJNR Am J Neuroradiol. 2008 May;29(5):913-8. Epub 2008 Mar 13

Petrou M, Harris RE, Foerster BR, McLean SA, Sen A, Clauw DJ, Sundgren PC.

BACKGROUND AND PURPOSE: Widespread pain sensitivity in patients with fibromyalgia (FM) suggests a central nervous system (CNS)-processing problem. Therefore, it is conceivable that metabolic alterations exist in pain-processing brain regions of people with FM compared with healthy controls (HC) and that such metabolic data could correlate with clinical symptoms. The purpose of this study was to test these hypotheses using proton MR spectroscopy ((1)H-MR spectroscopy). MATERIALS AND METHODS: There were 21 patients with FM and 27 HC who underwent conventional structural MR imaging and additional 2D-chemical shift imaging (CSI) MR-spectroscopy sequences. For the 2D-CSI spectroscopy, larger volumes of interest (VOIs) were centered at the level of the basal ganglia and the supraventricular white matter. Within these larger areas, 16 smaller voxels were placed in a number of regions previously implicated in pain processing. N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr and NAA/Cho ratios were calculated for each voxel. Subjects underwent clinical and experimental pain assessment. RESULTS: Mean metabolite ratios and ratio variability for each region were analyzed by using repeated-measures analysis of variance (ANOVA). Correlations between clinical symptoms and metabolite ratios were assessed. Cho/Cr variability in the right dorsolateral prefrontal cortex (DLPFC) was significantly different in the 2 groups; a significant correlation between Cho/Cr in this location and clinical pain was present in the FM group. Evoked pain threshold correlated significantly with NAA/Cho ratios in the left insula and left basal ganglia. CONCLUSION: Our data suggest that there are baseline differences in the variability of brain metabolite relative concentrations between patients with FM and HC, especially in the right DLPFC. Furthermore, there are significant correlations between metabolite ratios and clinical and experimental pain parameters in patients with FM.

Publication Types:

• Study

Hippocampus dysfunction may explain symptoms of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy

J Rheumatol. 2008 Jul;35(7):1371-7.

Emad Y, Ragab Y, Zeinhom F, El-Khouly G, Abou-Zeid A, Rasker JJ.

OBJECTIVE: (1) To investigate dysfunction of hippocampus in patients with fibromyalgia syndrome (FM) using proton magnetic resonance spectroscopy (1H-MRS), and to compare these findings with healthy controls. (2) To correlate levels of metabolites obtained with aspects of cognition, depression, and sleep symptoms in the patient group. METHODS: The case-control study was performed in 15 female patients, who met American College of Rheumatology criteria for classification of FM, and 10 healthy age-matched female controls. Patients and controls were receiving no medications known to affect cognitive functioning or central nervous system metabolites before their participation in the study. In all patients and controls, 1H-MRS was used to assess N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and their ratios from both hippocampi. Levels of metabolites and their ratios were determined and the findings compared between the groups. All patients and controls underwent psychological assessment to assess cognitive function, depression, and structured sleep interview with sleep diary; Fibromyalgia Impact Questionnaire (FIQ), number of tender points, and visual analog scale (VAS) for pain were assessed in all patients. RESULTS: NAA levels of right and left hippocampi differed significantly between patients and controls (p < 0.05). Cho levels in the right hippocampus were higher in the patient group than in controls (p = 0.005), while no differences were found with respect to Cr levels in both hippocampi. NAA/Cho and NAA/Cr ratios differed significantly between patients and controls (p <0.05), while the Cho/Cr ratio showed no differences. Significant correlations were found between language score and right Cho and right Cr levels (p = 0.041, p = 0.006, respectively), while no significant correlations were found between metabolites and their ratios with FIQ, VAS for pain, or number of tender points. CONCLUSION: The hippocampus was dysfunctional in patients with FM, as shown by lower NAA levels compared to controls, representing neuronal or axonal metabolic dysfunction. As the hippocampus plays crucial roles in maintenance of cognitive functions, sleep regulation, and pain perception, we suggest that metabolic dysfunction of hippocampus may be implicated in the appearance of these symptoms associated with this puzzling syndrome.

Publication Types:

• Review

Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features

J Pain. 2009 Jan;10(1):47-52

Wood PB, Ledbetter CR, Glabus MF, Broadwell LK, Patterson JC 2nd.

Although the pathology of fibromyalgia is poorly understood, a growing body of evidence suggests involvement of the central nervous system. The hippocampus is a brain center that is sensitive to the effects of stress exposure and has been demonstrated to be affected in a variety of disorders whose onset, like fibromyalgia, are associated with stressful experience. We therefore interrogated the bilateral hippocampus of 16 female fibromyalgia patients in comparison to 8 age- and gender-matched healthy control subjects using single voxel proton magnetic resonance spectroscopy. Our results demonstrate a significant reduction in the ratio of N-acetylaspartate to creatine (NAA/Cr) in fibromyalgia patients versus matched control subjects specifically in the right temporal lobe from a voxel centered on the right hippocampus (patient vs control, mean +/- standard deviation: 1.20 +/- 0.13 vs 1.34 +/- 0.10, P = .03). Moreover, correlation analysis demonstrated a significant negative correlation between patient scores on the Fibromyalgia Impact Questionnaire and NAA/Cr ratio within the right hippocampus (Spearman rank correlation, rho = -0.681, P = .018). Our results indicate that fibromyalgia is associated with brain metabolite abnormalities within the right hippocampus that correlate with patient symptoms. PERSPECTIVE: We have demonstrated an abnormality in hippocampal brain metabolites in premenopausal female fibromyalgia patients with no psychiatric comorbidity. A significant negative correlation between patient subjective experience of symptoms and a reduced NAA/Cr ratio suggests a role for hippocampal pathology in fibromyalgia

Publication Types:

• Study

Autonomic dysfunction in fibromyalgia syndrome: postural orthostatic tachycardia

Curr Rheumatol Rep. 2008 Dec;10(6):463-6

Staud R.

Although fibromyalgia (FM) syndrome is defined by chronic widespread pain and tenderness, additional symptoms, including disabling fatigue and dizziness, are often reported by patients with this chronic illness. Although nonrestorative sleep may play an important role for chronic fatigue in FM, other mechanisms, including dysfunction of the autonomic nervous system (ANS), need to be considered. Many important biological functions, such as heart rate, blood pressure, respirations, and bowel function, are tightly regulated by the ANS. However, dysfunction of the ANS is common in FM and often becomes quite apparent after positional changes from supine to upright. Although such positional changes sometimes result in syncope, they are more often associated with palpitations and dizziness. Head-up tilt table testing can be used to evaluate autonomic dysfunction and is frequently helpful for the work-up of FM complaints, including fatigue, dizziness, and palpitations. One of the most common events experienced by FM patients during tilt table testing is postural orthostatic tachycardia syndrome, which is defined as a heart rate increase of more than 30 beats per minute after more than 3 minutes of standing upright.

Publication Types:

• Review

Publication Types:

• Review