Neurobiology Underlying Fibromyalgia Symptoms

Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia symptoms to anatomical and functional brain changes. Neuroimaging studies show augmented sensory processing in pain-related areas, which, together with gray matter decreases and neurochemical abnormalities in areas related to pain modulation, supports the psychophysical evidence of altered pain perception and inhibition. Gray matter decreases in areas related to emotional decision making and working memory suggest that cognitive disturbances could be related to brain alterations. Altered levels of neurotransmitters involved in sleep regulation link disordered sleep to neurochemical abnormalities. Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or alterations, giving the long-held “it is all in your head” view of the disorder a new meaning

Fibromyalgia and Depression

Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromyalgia and depression and include laboratory findings on the role of depression in fibromyalgia. Further, we comment on several aspects of fibromyalgia which support the development of reactive depression, substantially more so than in other chronic pain syndromes. However, while sharing many features with depression, fibromyalgia is associated with somatic comorbidities and absolutely defined by fluctuating spontaneous widespread pain. Fibromyalgia may, therefore, be more appropriately grouped together with other functional pain disorders, while psychologically distressed subgroups grouped additionally or solely with affective spectrum disorders

Linear time reconstruction by discrete tomography in three dimensions

The goal of discrete tomography is to reconstruct an unknown function $f$ via a given set of line sums. In addition to requiring accurate reconstructions, it is favourable to be able to perform the task in a timely manner. This is complicated by the presence of switching functions, or ghosts, which allow many solutions to exist in general. In this paper we consider the case of a function $f : A \to \mathbb{R}$ where $A$ is a finite grid in $\mathbb{Z}^3$. Previous work has shown that in the two-dimensional case it is possible to determine all solutions in parameterized form in linear time (with respect to the number of directions and the grid size) regardless of whether the solution is unique. In this work, we show that a similar linear method exists in three dimensions under the condition of nonproportionality. This is achieved by viewing the three-dimensional grid along each 2D coordinate plane, effectively solving the problem with a series of 2D linear algorithms. We show that the condition of nonproportionality is fulfilled in the case of three-dimensional boundary ghosts, which motivated this research.Comment: 22 pages, 8 figures; submitted to Discrete Applied Mathematic

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, while c-Kit activation produces hypersensitivity to the noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study we investigated the role of c-Kit signalling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit, but also Abl1, PDFGFR{alpha}, and PDFGFR{beta}, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male, 17 female) under Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male, 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, while innocuous thermal and tactile thresholds were unchanged compared to the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity, but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to that of several common analgesics, thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans

Trace elements in ovaries: measurement and physiology

Traditionally, research in the field of trace element biology and human and animal health has largely depended on epidemiological methods to demonstrate involvement in biological processes. These studies were typically followed by trace element supplementation trials or attempts at identification of the biochemical pathways involved. With the discovery of biological molecules that contain the trace elements, such as matrix metalloproteinases containing zinc (Zn), cytochrome P450 enzymes containing iron (Fe), and selenoproteins containing selenium (Se), much of the current research focuses on these molecules, and, hence, only indirectly on trace elements themselves. This review focuses largely on two synchrotron-based x-ray techniques: X-ray absorption spectroscopy and x-ray fluorescence imaging that can be used to identify the in situ speciation and distribution of trace elements in tissues, using our recent studies of bovine ovaries, where the distribution of Fe, Se, Zn, and bromine were determined. It also discusses the value of other techniques, such as inductively coupled plasma mass spectrometry, used to garner information about the concentrations and elemental state of the trace elements. These applications to measure trace elemental distributions in bovine ovaries at high resolutions provide new insights into possible roles for trace elements in the ovary.Melanie J. Ceko, Sean O'Leary, Hugh H. Harris, Katja Hummitzsch, and Raymond J. Rodger

Speciation of copper in a range of food types by X-ray absorption spectroscopy

Abstract not availableMelanie J. Ceko, Jade B. Aitken, Hugh H. Harri

Error Correction for Discrete Tomography

Discrete tomography focuses on the reconstruction of functions $f: A \to \mathbb{R}$ from their line sums in a finite number $d$ of directions, where $A$ is a finite subset of $\mathbb{Z}^2$. Consequently, the techniques of discrete tomography often find application in areas where only a small number of projections are available. In 1978 M.B. Katz gave a necessary and sufficient condition for the uniqueness of the solution. Since then, several reconstruction methods have been introduced. Recently Pagani and Tijdeman developed a fast method to reconstruct $f$ if it is uniquely determined. Subsequently Ceko, Pagani and Tijdeman extended the method to the reconstruction of a function with the same line sums of $f$ in the general case. Up to here we assumed that the line sums are exact. In this paper we investigate the case where a small number of line sums are incorrect as may happen when discrete tomography is applied for data storage or transmission. We show how less than $d/2$ errors can be corrected and that this bound is the best possible