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Central sensitivity syndromes are characterized by distressing symptoms such as pain

Central sensitivity syndromes are characterized by distressing symptoms such as pain and fatigue in the absence of clinically obvious pathology. Neuroimaging studies of basal metabolism anatomic constitution molecular constituents evoked neural activity and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes which were historically considered to be completely of hysterical or feigned in origin. However whether sensory augmentation represents the cause of these syndromes a predisposing factor an endophenotype or an epiphenomenon cannot be discerned from the current literature. Further the result from cross-sectional neuroimaging studies of basal activity anatomy and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging “signature” cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time the existence of “central sensitivity syndromes” is based more soundly on clinical and epidemiological evidence. A coherent picture of a “central sensitization” mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence. tissue can also be performed. Two main techniques are currently in use. H-MRS can measure differences in proton resonance of a particular brain region yielding a discernable spectra allowing for determination of the region’s molecular constituents. Typically metabolites such as Glutamate Glutamate/Glutamine N-Acetylaspartate Choline and Creatine are measured and described as metabolite/Creatine ratios [19]. A second method uses Positron Emission Tomography (PET) with radiolabelled molecular Galanthamine hydrobromide ligands to measure the biological availability and tissue uptake. Ligands have been developed to specifically bind molecules such as opioid and dopamine receptors providing a surrogate measurement of receptor availability. Evoked Paradigms Evoked stimuli and evoked task neuroimaging paradigms are the most common neuroimaging designs used in neuroimaging research. Simply stated evoked paradigms take measurements of brain activity patterns during the administration of stimuli or performance of a particular task. Neural activity causes discreet localized alterations in regional cerebral blood flow (rCBF). This observation is used to infer neural activity from changes in rCBF. Thus these paradigms take advantage of a quintessential scientific observation [20] that the relationship between mental activity and moment-to-moment cerebral blood flow are both predictable and replicable. It Galanthamine hydrobromide is now well established that particular mental activities are associated with surrogate patterns of alterations in the spatial distribution of cerebral blood flow rates [21]. The most common method to measure surrogates of experimentally-evoked neural activity is fMRI Blood Oxygen-Dependent Level (BOLD) imaging. Unlike WAF1 methods such as positron emission tomography (PET) that use an injectable tracer the BOLD technique takes advantage of the magnetic character of deoxygenated hemoglobin which suppresses the fMRI signal from surrounding tissue. The increase in rCBF in Galanthamine hydrobromide response to increased neural activity provides more oxygenated blood than is required to meet the metabolic needs of the active neurons. This oxygenated hemoglobin has less magnetic character resulting in less suppression in tissue and a corresponding increase in the fMRI signal. These fluctuations in regional blood oxygenation and the Galanthamine hydrobromide resulting Galanthamine hydrobromide signal can be spatially measured in three dimensions to millimeter accuracy using fMRI. Since its inception BOLD fMRI has been applied to a vast number of scientific questions and has transformed the state of neurological sciences. One field that has been transformed by the advent of BOLD imaging is the study of pain. Evoked pain paradigms have been able to determine that painful experiences have a recognizable BOLD signature that we describe here as “pain-related networks”. Different types of painful stimulation lead to a similar patterns Galanthamine hydrobromide of increased BOLD activity. The pain-related networks (see Fig. 1) consist primarily of the thalamus primary somatosensory cortex (S1) posterior parietal cortex (PPC) anterior.