Neuroscience
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The gate control theory proposed that the nociceptive sensory information transmitted to the brain relies on an interplay between the inputs from nociceptive and non-nociceptive primary afferent fibers. Both inputs are normally under strong inhibitory control in the spinal cord. ⋯ However, under pathological conditions, this spinal inhibition may be altered and lead to chronic pain. This review summarizes our knowledge of presynaptic inhibition in pain control, with particular focus on how its alteration after nerve or tissue injury contributes to neuropathic or inflammatory pain syndromes, respectively.
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Injury to the adult nervous system promotes the expression and secretion of brain-derived neurotrophic factor (BDNF). Because it promotes neuronal growth, survival and neurogenesis, BDNF may initiate compensatory processes that mitigate the deleterious effects of injury, disease or stress. Despite this, BDNF has been implicated in several injury-induced maladaptive processes including pain, spasticity and convulsive activity. ⋯ BDNF effects are confined to changes in synaptic transmission as there is little change in the passive or active properties of neurons in the superficial dorsal horn. Actions of BDNF in the brain stem and periphery also contribute to the onset and persistence of chronic pain. In spite of its role in compensatory processes that facilitate the recovery of the nervous system from injury, the widespread maladaptive actions of BDNF mean that there is literally "no gain without pain".
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Non-invasive criteria determining the progress of brain healing are especially important in aging, providing a case-specific therapeutic strategy in populations with dysregulated neurorepair mechanisms. We hypothesized that temporal evolution of magnetic resonance imaging (MRI) of T2 tissue relaxation values correlate with neurological severity scores (NS), and provide a robust indicator of healing in the aging brain after stroke. Pre-treatment of aged rats with brain-only proton irradiation was undertaken to pre-condition the inflammatory system. ⋯ We also found reduced infiltration of T-lymphocytes (CD3) in the brain and normalization of blood lymphocytes. The observed T2-NS correlations may provide a simple MRI-based criterion for recognition of regenerative brain transformation in aged patients following stroke. Selective activation of innate immunity and accelerated transition from pro-inflammatory to pro-healing macrophage phenotypes induced by localized brain irradiation is a potential mechanism for enhancing repair ability in the elderly.
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The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. ⋯ This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain.
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The functions of the D1- and D2-dopamine receptors in the basal ganglia have remained somewhat enigmatic, with a number of competing theories relating to the interactions of the 'direct' and 'indirect pathways'. Computational models have been good at simulating properties of the system, but are typically divorced from the underlying neural architecture. ⋯ The D2DR-expressing striatal pathways then shape and 'select' from this initial response set framework. This article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine.