Brain research
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Intraplantar administration of zymosan produces inflammation and results in behavioral evidence of hyperalgesia to mechanical and thermal stimuli in the rat. In the present studies, responses of primary afferents and spinal dorsal horn neurons to mechanical and thermal stimuli were examined before and during zymosan-induced inflammation of the hindpaw. In tests of responses of primary afferents to mechanical stimuli, group mean mechanical response thresholds of C-mechanonociceptor (CMN) units significantly decreased after zymosan administration. ⋯ These data suggest that the zymosan-induced hyperalgesia to mechanical stimuli observed in behavioral studies reflects decreases in response thresholds of peripheral CMN units and spinal NS neurons. Hyperalgesia to thermal stimuli reflects decreases in response thresholds of peripheral CMH units, spinal WDR neurons, and spinal NS neurons. These data support the view that different physiological substrates mediate hyperalgesia to either thermal or mechanical stimuli following intraplantar administration of zymosan.
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In animal models of neuropathic pain, transection or constrictive injury to peripheral nerves produces ectopic discharges originating at both injury sites and related dorsal root ganglia (DRG). In addition, hyperexcitability is observed in associated dorsal horn (DH) neurons of the spinal cord. As ectopic discharges are inhibited by agents that block voltage-sensitive Na+ channels, it has been postulated that accumulation of Na+ channels in the membrane at nerve injury sites may contribute to the development of ectopic nerve activity (ENA). ⋯ Lidocaine or QX-314 also significantly reduced HR and MBP in the same dose range as that which reduced ENA in DRG or neuromas. In isolated rat vagus nerve recordings, QX-314 induced marked use-dependent inhibition of C-spike amplitude, with IC50 values (microM) of 9000 (4600-18,000) and 350 (290-420) for low- (0.03 Hz) and high-frequency (30 Hz) C-spikes, respectively. These data support the hypothesis that Na+ channel accumulation contributes to the generation of ectopic discharges in neuromas and DRG, and suggests that intravenous QX-314 can acutely block Na+ channels at these sites.
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We evaluated the modulatory effect of the GABA-active neurosteroid alphaxalone on the staircase test behavior of mice. Results were compared with the benzodiazepine alprazolam, the GABA(A) agonist muscimol and the peripheral steroids corticosterone and progesterone. Alphaxalone and alprazolam reduced rearing activity in a dose-dependent manner, at doses that did not suppress climbing. ⋯ No such dissociation between the effect on rearing and climbing was obtained with muscimol, and both activities were suppressed, in a flumazenil-insensitive pattern, at high doses. Corticosterone and progesterone did not affect the behavior of the mice. The lack of sensitivity of both phenobarbital and alphaxalone to flumazenil indicates that neither agents act via the benzodiazepine recognition site at the GABA(A) receptor complex.
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In the present study we examined the laminar distributions of four types of chemically defined subpopulations of non-principal neurons, that is, those immunoreactive for parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) and somatostatin (SS), in the rat hippocampus, by estimating their approximate numerical densities (NDs) and percentages in specific layers according to the 'disector' principle. CR-immunoreactive (CR-IR) neurons and NOS-IR neurons were scattered throughout layers, but among layers in each subdivision their NDs were largest in the principal cell layers, where 30-45% of CR-IR and NOS-IR somata in each subdivision were located. In addition, CR-IR and NOS-IR somata were also concentrated at the border between the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) in the CA1 region, where the NDs of these neurons were far larger than those in the SR/SLM as a whole and close to those in the stratum pyramidale (SP) (CR-IR somata at the ventral level and NOS-IR somata at the dorsal level) or larger (NOS-IR neurons at the ventral level). ⋯ The NDs in the SP of the CA1 and CA3 regions showed a significant dorsoventral difference. Although PV-IR somata were most numerous among the four non-principal cell groups in the SP of the dorsal CA1 region, they were not necessarily predominant in the principal layers in other regions, that is, in the ventral CA1 region, CA3 region and DG, where the NDs of CR-IR and/or NOS-IR somata were nearly equal to or larger than that of PV-IR somata. The present study not only reveals the laminar distribution patterns of four types of non-principal neurons in each subdivision quantitatively, but also illustrates the prominent differences in the compositions of four types of non-principal cells in each layer of each subdivision.
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Intensities of the immunoreactivities against two GAD isoforms, GAD65 and GAD67, were examined quantitatively in somata of GABAergic neurons in the mouse hippocampus proper. All labeled somata contained both isoforms but showed diverse immunoreactivities against them. The somata showing weak immunoreactivity for GAD65 but moderate to intense immunoreactivity for GAD67 were frequently located in the stratum pyramidale of the CA1 and CA3 regions and were mainly composed of parvalbumin-containing neurons, a particular subpopulation of hippocampal GABAergic neurons. These data revealed additional distinctive properties of parvalbumin-containing neurons and suggest their specialized roles in the hippocampal GABAergic system.