The Journal of neuroscience : the official journal of the Society for Neuroscience
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We investigated the ability of human nociceptive primary afferent neurons to encode mechanical pain and to produce vasodilatation. Pain was induced by shooting a light metal cylinder (0.3 g) at different velocities (6-18 m/sec) perpendicularly against the hairy skin of the hand. When single impact stimuli were applied, monotonically increasing stimulus-response functions were obtained in 10 psychophysical experiments using magnitude estimation techniques. ⋯ This suggests that temporal summation of the nociceptive discharge at central neurons becomes increasingly more important for the sensory discriminative experience of pain evoked by repetitive stimulation. We conclude that human nociceptive C-fibers signal brief noxious mechanical stimuli by the total number of action potentials evoked during a short period of time. However, with repetitive stimulation the total number of action potentials evoked from nociceptors is less important for evoking pain and temporal summation of the nociceptive primary afferent discharge becomes the crucial factor for signaling the magnitude of sensation.
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The use of human Schwann cells (SCs) in transplantation to promote regeneration in central and peripheral neural tissues must be preceded by efforts to define the factors that regulate their functional expression. Adult-derived human SCs can be isolated and purified in culture, but the culture conditions that allow their full differentiation have not yet been defined. We tested the functional capacity of these cells to enhance axonal regeneration and myelinate regenerating axons in vivo by transplanting them into the damaged PNS of an immune-deficient rat. ⋯ The number of myelinated axons and the cross-sectional area of the cable were significantly greater in channels seeded with human SCs when compared to channels containing the diluted Matrigel solution alone. We conclude that purified cultured human SCs can survive and substantially enhance axonal regeneration when transplanted into the injured PNS of an immune-deficient rat. Some of the transplanted human SCs are capable of myelinating regenerating rat axons but are less successful than the host SCs.
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The basal ganglia receive massive inputs from the neocortex and send outputs that exert both inhibitory and disinhibitory control over parts of the frontal cortex and brainstem. Between these basal ganglia inputs and outputs lies the striatum, which receives most of the cortical afferents and projects to the basal ganglia output nuclei--the globus pallidus and substantia nigra. To analyze this system we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the striatum and striatal outputs to the globus pallidus. ⋯ One function of striatal modularity may thus be to set up an associative network in the striatum, which might contribute to sensorimotor learning. We also found that some sets of matrisomes did not receive strong sensorimotor inputs, even though they projected to regions of GPe and GPi that are near the sensorimotor-recipient zones described above. Thus, the matrisomal system may sort MI/SI inputs and other inputs before transfer to paired regions of GPe and GPi.
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Substance P (SP) and other related tachykinins such as neurokinin B (NKB) have been studied widely as mediators of sensory information. The release of SP into the dorsal horn of the spinal cord is increased during nociception, and SP activates nociception-specific dorsal horn neurons. The tachykinin NKB has antinociceptive effects in the spinal cord and is contained in intrinsic spinal neurons; thus, NKB may also contribute to the processing of sensory information. ⋯ Peptide and receptor mRNA expression levels were normalized to beta-actin mRNA levels, which did not change during the treatments. Formalin (2 or 6 hr) or CFA (4 d) injection produced approximately a twofold increase in SP-encoding PPT mRNA expression in the ipsilateral lumbar DRG. Increased activity in primary afferent neurons containing SP may stimulate the production of SP precursors, providing substrate for increased SP production, release, and turnover in the dorsal horn and periphery.(ABSTRACT TRUNCATED AT 250 WORDS)
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Potential cellular substrates for functions ascribed to the dopamine D2 receptor were examined in rat brain using immunoperoxidase for localization of a D2 receptor peptide and immunogold staining for the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH). Specificity of the rat polyclonal antiserum, raised against a 15 amino acid fragment from the third intracellular loop of the D2 receptor, was shown by immunoblot analysis and by selective labeling of cultured Chinese hamster ovary cells permanently transfected with the cDNA for the D2 receptor. Although the light microscopic distribution of immunolabeling for the D2 peptide was diffuse, it was selectively localized to regions containing dopamine cells (substantia nigra and ventral tegmental area) or their forebrain projections (dorsal and ventral striatum, nucleus accumbens, and olfactory tubercles). ⋯ In dually labeled sections, most D2 peptide-immunoreactive terminals lacked detectable immunolabeling for TH. However, in fortunate planes of section, peroxidase product for D2 peptide immunoreactivity was occasionally seen in pre-terminal portions of axons whose terminal varicosities contained immunogold labeling for TH. These ultrastructural results are consistent with the localization of a dopamine D2 receptor-like protein that is strategically positioned to subserve (1) autoreceptor functions at the level of dendrites in the midbrain and presynaptic axon terminals in the striatum, as well as (2) postsynaptic actions on striatal spiny dendrites and other nondopamine terminals.