Neuroscience
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The present study aimed to investigate whether tonic cutaneous pain exerts any effect on the cortical processing of nociceptive input and if this effect may involve only body parts in pain. Tonic cutaneous pain was obtained in nine healthy human subjects by infusion of a hypertonic saline (5%) in the s.c. tissue over the hypothenar muscles (10 ml/h for 20 min). Nociceptive cutaneous CO2 laser-evoked potentials were recorded after stimulation of the right hand dorsum, which was adjacent to the painful area, and the right perioral region, corresponding to the adjacent cortical sensory area. ⋯ Dipolar modeling showed that the dipolar source in the anterior cingulate cortex moved backward during saline infusion. This result suggests that cutaneous pain may modify the relative activities of the anterior and posterior anterior cingulate cortex parts, which are thought to be devoted to encode different aspects of pain sensation. No laser-evoked potential change was observed after stimulation of the right perioral region, suggesting that functional changes in the nociceptive system are selective for the painful regions and not for areas with cortical proximity.
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Accumulating evidences suggest that neuroinflammation is involved in the progressive death of dopaminergic neurons in Parkinson's disease. Several studies have shown that intranigral injection of lipopolysaccharide induces inflammation in the substantia nigra leading to death of tyrosine hydroxylase-positive cells. To better understand how the inflammatory response gives rise to neurotoxicity we induced inflammation in substantia nigra by injecting lipopolysaccharide. ⋯ Co-injections of lipopolysaccharide with SB203580, a p38 MAP kinase inhibitor, reduced inducible nitric oxide synthase and caspase-11 mRNA expression, and also rescued dopaminergic neurons in substantia nigra. In summary, this is the first report to describe in vivo the temporal profile of the expression of these inflammatory mediators and proteins involved in dopaminergic neuronal death after intranigral injection of lipopolysaccharide. Moreover data strongly support that lipopolysaccharide-induced dopaminergic cellular death in substantia nigra could be mediated, at least in part, by the p38 signal pathway leading to activation of inducible nitric oxide synthase and caspase-11.
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Comparative Study
Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization.
Nerve injury can produce hypersensitivity to noxious and normally innocuous stimulation. Injury-induced central (i.e. spinal) sensitization is thought to arise from enhanced afferent input to the spinal cord and to be critical for expression of behavioral hypersensitivity. Descending facilitatory influences from the rostral ventromedial medulla have been suggested to also be critical for the maintenance, though not the initiation, of experimental neuropathic pain. ⋯ In contrast, nerve-injured animals pretreated with dermorphin-saporin showed enhanced behaviors and touch-evoked FOS expression in the spinal dorsal horn at day 3, but not days 5 and 10, post-spinal nerve ligation when compared with sham-operated controls. These results indicate the presence of nerve injury-induced behavioral hypersensitivity associated with nerve injury-induced central sensitization. Further, the results demonstrate the novel concept that once initiated, maintenance of nerve injury-induced central sensitization in the spinal dorsal horn requires descending pain facilitation mechanisms arising from the rostral ventromedial medulla.
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The ability of exercise to benefit neuronal and cognitive plasticity is well recognized. This study reveals that the effects of exercise on brain neuronal and cognitive plasticity are in part modulated by a central source of insulin-like growth factor-I. Exercise selectively increased insulin-like growth factor-I expression without affecting insulin-like growth factor-II expression in the rat hippocampus. ⋯ A molecular analysis revealed that exercise significantly elevated proteins downstream to brain-derived neurotrophic factor activation important for synaptic function, i.e. synapsin I, and signal transduction cascades associated with memory processes, i.e. phosphorylated calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein kinase II. Blocking the insulin-like growth factor-I receptor abolished these exercise-induced increases. Our results illustrate a possible mechanism by which insulin-like growth factor-I interfaces with the brain-derived neurotrophic factor system to mediate exercise-induced synaptic and cognitive plasticity.
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Before exocytotic release of the inhibitory neurotransmitter GABA, this amino acid has to be stored in synaptic vesicles. Accumulation of GABA in vesicles is achieved by a specific membrane-integrated transporter termed vesicular GABA transporter. This vesicular protein is mainly located at presynaptic terminals of GABAergic interneurons. ⋯ Vesicular GABA transporter protein-containing synaptic terminals and somata were visualized by immunohistochemistry. The pattern of vesicular GABA transporter immunoreactivity as well as the protein expression level revealed by semiquantitative image analysis and by Western blot remained stable after stroke. The steady expression of vesicular GABA transporter mRNA and protein after photothrombosis indicates that the exocytotic release mechanism of GABA is not affected by ischemia.