Developments in the scientific and clinical understanding of fibromyalgia

Our understanding of fibromyalgia (FM) has made significant advances over the past decade. The current concept views FM as the result of central nervous system malfunction resulting in amplification of pain transmission and interpretation. Research done over the past years has demonstrated a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FM. Various external stimuli such as infection, trauma and stress may contribute to the development of the syndrome. The management of FM requires an integrated approach combining pharmacological and nonpharmacological modalities. The recent Food and Drugs Administration approval of pregabalin, duloxetine and milnacipran as medications for FM may herald a new era for the development of medications with higher specificity and efficacy for the condition. As our understanding of the biological basis and the genetic underpinning of FM increases, we hope to gain a better understanding of the true nature of the disorder, to better classify patients and to attain more rational therapeutic modalities

Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome

Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients. The mode of inheritance is unknown but it is most probably polygenic. There is evidence that polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems play a role in the etiology of FMS. These polymorphisms are not specific for FMS and are associated with other functional somatic disorders and depression. Future genetic studies in the field of FMS and related conditions should be conducted in larger cohorts of patients and ethnically matched control groups

Spa Treatment (Balneotherapy) for Fibromyalgia—A Qualitative-Narrative Review and a Historical Perspective

Aim. To perform a narrative review of spa therapy for management of the fibromyalgia syndrome (FMS), evaluating this traditional time-honored form of therapy in a historical perspective. Methods. Medline was searched using the terms “Spa therapy,” “Balneotherapy,” and “Fibromyalgia” between 1990 (year of ACR fibromyalgia criteria publication) and April 2013. The Cochrane database was also searched. Publications relating to the implementation of spa therapy and related practices over the centuries were identified through references, searched, and reviewed. Results. Reports of balneotherapy were described from diverse locations throughout Europe and Asia, and various forms of water-related therapy have been incorporated for many musculoskeletal indications. In the management of FMS, spa therapy has generally been shown to be well accepted and moderately effective for symptom reduction. Conclusion. While achieving high-quality evidence-based conclusions is difficult for complex natural therapies such as spa therapy, the existing evidence indicates a positive effect in management of FMS. In view of the long history of this modality in the management of rheumatic pain as well as the inherent difficulties related to pharmacological treatment, the role of spa therapy should currently be recognized as part of a therapeutic program for FMS

Astrocytic modulation of neuronal signalling

Neuronal signalling is a key element in neuronal communication and is essential for the proper functioning of the CNS. Astrocytes, the most prominent glia in the brain play a key role in modulating neuronal signalling at the molecular, synaptic, cellular, and network levels. Over the past few decades, our knowledge about astrocytes and their functioning has evolved from considering them as merely a brain glue that provides structural support to neurons, to key communication elements. Astrocytes can regulate the activity of neurons by controlling the concentrations of ions and neurotransmitters in the extracellular milieu, as well as releasing chemicals and gliotransmitters that modulate neuronal activity. The aim of this review is to summarise the main processes through which astrocytes are modulating brain function. We will systematically distinguish between direct and indirect pathways in which astrocytes affect neuronal signalling at all levels. Lastly, we will summarize pathological conditions that arise once these signalling pathways are impaired focusing on neurodegeneration

Synthesis of neural networks for spatio-temporal spike pattern recognition and processing

The advent of large scale neural computational platforms has highlighted the lack of algorithms for synthesis of neural structures to perform predefined cognitive tasks. The Neural Engineering Framework offers one such synthesis, but it is most effective for a spike rate representation of neural information, and it requires a large number of neurons to implement simple functions. We describe a neural network synthesis method that generates synaptic connectivity for neurons which process time-encoded neural signals, and which makes very sparse use of neurons. The method allows the user to specify, arbitrarily, neuronal characteristics such as axonal and dendritic delays, and synaptic transfer functions, and then solves for the optimal input-output relationship using computed dendritic weights. The method may be used for batch or online learning and has an extremely fast optimization process. We demonstrate its use in generating a network to recognize speech which is sparsely encoded as spike times.Comment: In submission to Frontiers in Neuromorphic Engineerin

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300–400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABAA blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity

Generating brain waves, the power of astrocytes

Synchronization of neuronal activity in the brain underlies the emergence of neuronal oscillations termed “brain waves”, which serve various physiological functions and correlate with different behavioral states. It has been postulated that at least ten distinct mechanisms are involved in the formulation of these brain waves, including variations in the concentration of extracellular neurotransmitters and ions, as well as changes in cellular excitability. In this mini review we highlight the contribution of astrocytes, a subtype of glia, in the formation and modulation of brain waves mainly due to their close association with synapses that allows their bidirectional interaction with neurons, and their syncytium-like activity via gap junctions that facilitate communication to distal brain regions through Ca2+ waves. These capabilities allow astrocytes to regulate neuronal excitability via glutamate uptake, gliotransmission and tight control of the extracellular K+ levels via a process termed K+ clearance. Spatio-temporal synchrony of activity across neuronal and astrocytic networks, both locally and distributed across cortical regions, underpins brain states and thereby behavioral states, and it is becoming apparent that astrocytes play an important role in the development and maintenance of neural activity underlying these complex behavioral states

Neuromodulation of glial function during neurodegeneration

Glia, a non-excitable cell type once considered merely as the connective tissue between neurons, is nowadays acknowledged for its essential contribution to multiple physiological processes including learning, memory formation, excitability, synaptic plasticity, ion homeostasis, and energy metabolism. Moreover, as glia are key players in the brain immune system and provide structural and nutritional support for neurons, they are intimately involved in multiple neurological disorders. Recent advances have demonstrated that glial cells, specifically microglia and astroglia, are involved in several neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), Epilepsy, Parkinson’s disease (PD), Alzheimer’s disease (AD), and frontotemporal dementia (FTD). While there is compelling evidence for glial modulation of synaptic formation and regulation that affect neuronal signal processing and activity, in this manuscript we will review recent findings on neuronal activity that affect glial function, specifically during neurodegenerative disorders. We will discuss the nature of each glial malfunction, its specificity to each disorder, overall contribution to the disease progression and assess its potential as a future therapeutic target

Spa treatment (Balneotherapy) for fibromyalgia—a qualitative-narrative review and a historical perspective

Aim. To perform a narrative review of spa therapy for management of the fibromyalgia syndrome (FMS), evaluating this traditional time-honored form of therapy in a historical perspective. Methods. Medline was searched using the terms "Spa therapy, " "Balneotherapy, " and "Fibromyalgia" between 1990 (year of ACR fibromyalgia criteria publication) and April 2013. The Cochrane database was also searched. Publications relating to the implementation of spa therapy and related practices over the centuries were identified through references, searched, and reviewed. Results. Reports of balneotherapy were described from diverse locations throughout Europe and Asia, and various forms of water-related therapy have been incorporated for many musculoskeletal indications. In the management of FMS, spa therapy has generally been shown to be well accepted and moderately effective for symptom reduction. Conclusion. While achieving high-quality evidence-based conclusions is difficult for complex natural therapies such as spa therapy, the existing evidence indicates a positive effect in management of FMS. In view of the long history of this modality in the management of rheumatic pain as well as the inherent difficulties related to pharmacological treatment, the role of spa therapy should currently be recognized as part of a therapeutic program for FMS