Neuroscience
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Neuropathic pain resulting from spinal cord injury is often accompanied by maladaptive plasticity of the central nervous system, including the opioid receptor-rich periaqueductal gray (PAG). Evidence suggests that sensory signaling via the PAG is robustly modulated by dopamine D1- and D2-like receptors, but the effect of damage to the spinal cord on D1 and D2 receptor protein expression and function in the PAG has not been examined. Here we show that 21days after a T10 or C6 spinothalamic tract lesion, both mice and rats display a remarkable decline in the expression of D1 receptors in the PAG, revealed by western blot analysis. ⋯ Using immunohistochemistry, we found that SKF 81297 increased ERK1,2 phosphorylation in the PAG of sham animals. However, in lesioned animals, basal pERK1,2 levels were elevated and did not significantly increase after exposure to SKF 81297. Our findings provide support for the hypothesis that molecular adaptations resulting in a decrease in D1 receptor expression and signaling in the PAG are a consequence of SCL.
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Perceiving and reproducing direction of visual stimuli in 2-D space produces the visual oblique effect, which manifests as increased precision in the reproduction of cardinal compared to oblique directions. A second cognitive oblique effect emerges when stimulus information is degraded (such as when reproducing stimuli from memory) and manifests as a systematic distortion where reproduced directions close to the cardinal axes deviate toward the oblique, leading to space expansion at cardinal and contraction at oblique axes. We studied the oblique effect in 3-D using a virtual reality system to present a large number of stimuli, covering the surface of an imaginary half sphere, to which subjects had to reach. ⋯ A visual oblique effect was observed for the reproduction of cardinal directions compared to oblique, which did not differ with memory condition. A cognitive oblique effect also emerged, which was significantly larger in the memory compared to the no-memory condition, leading to distortion of directional space with expansion near the cardinal axes and compression near the oblique axes on the hemispherical surface. This effect provides evidence that existing models of 2-D directional space categorization could be extended in the natural 3-D space.
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The prefrontal cortex (PFC) plays a key role in cognitive functions, memory, and attention. Alterations in parvalbumin interneurons (PV neurons) and perineuronal nets (PNNs) within the PFC have been implicated in schizophrenia and autism spectrum disorder pathology. However, it remains unclear why PV neurons and PNNs in the PFC are selectively impaired. ⋯ In the mature PFC, the expression of PV protein is lower than in other parts of the cortex. Furthermore, PNNs in the mature PFC are not typical lattice-like structures and do not have the major components of PNNs and tenascin-R. The present study indicates that PV neurons and PNNs have region-specific features, and our results suggest that PV neurons and PNNs have structural vulnerability within the PFC.
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Fibromyalgia is the current term for chronic widespread musculoskeletal pain for which no alternative cause can be identified. The underlying mechanisms, in both human and animal studies, for the continued pain in individuals with fibromyalgia will be explored in this review. There is a substantial amount of support for alterations of central nervous system nociceptive processing in people with fibromyalgia, and that psychological factors such as stress can enhance the pain experience. ⋯ We will explore the data and neurobiology related to the role of the CNS in nociceptive processing, followed by a short review of studies examining potential peripheral nervous system changes and cytokine involvement. We will not only explore the data from human subjects with fibromyalgia but will relate this to findings from animal models of fibromyalgia. We conclude that fibromyalgia and related disorders are heterogenous conditions with a complicated pathobiology with patients falling along a continuum with one end a purely peripherally driven painful condition and the other end of the continuum is when pain is purely centrally driven.
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This review addresses the fundamental question of how we first experience pain, at the beginning of our lives. The brain is activated by peripheral tissue damaging stimulation from birth, but unlike other sensory systems, the pain system in healthy individuals cannot rely upon prolonged activity-dependent shaping through repeated noxious stimulation. Considering the importance of pain, remarkably little is known about when and how nociceptive cortical network activity characteristic of the mature adult brain develops. ⋯ Since this developing brain connectome is necessary, if not sufficient, for pain experience, we discuss the structural and functional development of cortical and subcortical networks that contribute to this network. We then review specific information on the development of nociceptive processing in the infant brain, considering evidence from neurophysiological and hemodynamic measures separately, as the two are not always consistent. Finally we highlight areas that require further research and discuss how information gained from laboratory animal models will greatly increase our understanding in this area.