Neuroscience
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Abnormal pain-related behaviour that accompanies peripheral nerve injury may be the result of altered spinal neuronal function. The long-term loss of inhibitory function by GABA neurons in particular may be a mechanism by which abnormal neural hyperactivity occurs, leading to exaggerated sensory processing following nerve injury. In order to assess this, changes in spinal GABA immunoreactivity at several time points following constriction nerve injury were quantified in parallel with behavioural assessments of abnormal sensory responses to noxious and innocuous stimuli. ⋯ Parallel improvements in sensory responses to innocuous and noxious stimuli were also observed in these animals. The results of this study indicate that peripheral nerve injury can result in severe losses in spinal inhibitory mechanisms, possibly leading to exaggerated sensory processes in persistent pain states. In addition, adrenal medullary transplants may provide a neuroprotective function in promoting recovery and improving long-term survival of GABAergic neurons in the spinal dorsal horn which have been damaged by excitotoxic injury.
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The method of transneuronal retrograde transport of the Bartha strain of the swine alpha-herpes virus, pseudorabies virus, was used to identify putative interneurons presynaptic to motoneurons that supply a tail-flick muscle in the rat. We also investigated whether these interneurons also contribute to ascending somatosensory pathways. Two to five days after injection of pseudorabies virus into the left abductor caudae dorsalis muscle, and cholera toxin B into the right somatosensory thalamus and midbrain, rats were perfused and spinal cord sections processed immunohistochemically in a two-step procedure to stain cholera toxin B-immunoreactive cells black and pseudorabies virus-immunoreactive cells brown. ⋯ We also suggest that some lamina II cells are presynaptic to lamina I cells that project directly to abductor caudae dorsalis motoneurons. We observed cholera toxin B-immunoreactive cells (five to 20/section) in the expected locations (contralateral lamina I, deep dorsal horn and intermediate zone; lateral spinal nucleus bilaterally). Double-labeled (i.e. pseudorabies virus- and cholera toxin B-immunoreactive) neurons were only occasionally seen in the lateral spinal nucleus and were absent in the spinal gray matter, indicating that segmental interneurons do not collateralize in long ascending sensory pathways to the midbrain and somatosensory thalamus.
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Intracellular microelectrodes were used to examine the active and passive membrane properties of neurons in the myenteric plexus of the guinea-pig small intestine. Neurons of two types were examined: S neurons, which have prominent fast excitatory postsynaptic potentials and in which action potentials are not followed by long-lasting afterhyperpolarizations, and AH neurons, which have long-lasting afterhyperpolarizations following soma action potentials. In preparations in which the myenteric ganglia and longitudinal muscle, but no mucosa, were present, most S neurons (59/64) responded to intracellular depolarizing current with brief bursts of action potentials. ⋯ Spontaneous antidromic action potentials were recorded in 8/62 AH neurons within 600 microm circumferential to the intact mucosa. It is concluded that, when the mucosa is intact, a background firing of sensory neurons occurs which leads to a state change in many S neurons innervated by the active sensory neurons. We conclude that this state change is caused by the block of a voltage-sensitive outward rectification.
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The effects of pretreatment with a protein kinase C activator, phorbol 12,13-dibutyrate, on antinociception induced by i.c.v.-administered mu-opioid receptor agonist (D-Ala2, NMePhe4, Gly(ol)5) enkephalin (DAMGO) or morphine and epsilon-opioid receptor agonist beta-endorphin were studied in male ICR mice. The tail-flick responses were used for antinociceptive tests. I.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol) for 30 or 60 but not 10 min attenuated antinociception induced by i.c.v.-administered DAMGO. ⋯ The attenuation of i.c.v.-administered DAMGO- and morphine-induced antinociception by phorbol 12,13-dibutyrate was reversed by concomitant i.c.v. pretreatment with a selective protein kinase C inhibitor calphostin C. These results suggest that activation of protein kinase C by phorbol 12,13-dibutyrate leads to the desensitization of mu-, but not epsilon-opioid receptor-mediated antinociception. These findings also provide additional evidence for differential intracellular modulation on antinociceptive action of mu- and epsilon-opioid receptor agonists.
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A set of well-defined antisera against neuronal and glial proteins were used to characterize patterns of protein expression in rat hippocampus following transection of the fimbira-fornix and perforant pathways or after administration of the selective neurotoxicant trimethyltin (8 mg/kg, i.p.). SNAP-25 (synaptosomal protein, mol. wt 25,000) is a neuron-specific, developmentally regulated presynaptic protein, stannin is a protein enriched in cells sensitive to trimethyltin, and GAP-43 (growth-associated protein, mol. wt 43,000) is associated with axonal growth and regeneration. Glial fibrillary acidic protein is an astrocyte-specific intermediate filament protein and a marker for reactive gliosis. ⋯ Immunoblot analysis showed that only the adult SNAP-25b isoform was expressed after trimethyltin intoxication. These data suggest that SNAP-25 is a useful marker for presynaptic damage. Furthermore, reexpression of developmental isoforms of SNAP-25a may precede functional reinnervation when the postsynaptic target remains intact.