Neuroscience
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While enhanced nociceptor activity has been demonstrated in models of painful peripheral neuropathy, analyses of activity pattern, which could play a role in the symptoms experienced as well as help elucidate underlying mechanism, are still limited. We evaluated the pattern of C-fiber activity, in response to mechanical and chemical stimuli, in a rat model of diabetes induced by a pancreatic beta-cell toxin, streptozotocin (STZ). In diabetic rats the number of action potentials produced by threshold and suprathreshold (10 g) sustained (60 s) mechanical stimuli was elevated in approximately half of C-fibers. ⋯ The number of action potentials evoked by a noxious chemical stimulus, 300 and 600 mM KCl, injected adjacent to the mechanical receptive field was also significantly increased in C-fibers from diabetic rats and mechanically high-firing fibers had more action potentials in response to KCl than control fibers and a disproportionate increase in ISIs between 100 and 199 ms for responses to chemical stimuli appeared only in mechanically high-firing C-fibers, compared with the mechanically low-firing diabetic or control C-fibers. There was, however, no corresponding change in CV2 or instantaneous frequency plots for the response to chemical stimulation in mechanically high-firing fibers, as there was in the response to mechanical stimulation. Our data demonstrate specific changes in firing pattern of high-firing C-fibers in the rat model of painful neuropathy produced by STZ-diabetes that might contribute to the symptoms experienced by patients.
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The immunomodulatory thymic hormone thymulin has been shown previously to possess anti-inflammatory actions in the periphery. In this study, we have examined the effect of i.c.v. injections of either endotoxin (ET) or thymulin, in separate groups of conscious rats, on pain-related behavior and cytokine levels in different areas of the brain. Furthermore, we investigated the effect of pretreatment with either i.c.v. or i.p. injections of thymulin on endotoxin-induced hyperalgesia and the effect of pretreatment with i.c.v. thymulin on endotoxin-induced up-regulation of cytokine levels. ⋯ However, thymulin at different doses, when injected (i.c.v.), had no significant effect on pain related behavior. Pretreatment (i.c.v.) with thymulin (0.1, 0.5 and 1 microg in 5 microl saline) 20 min before endotoxin (i.c.v.) injection (1 microg in 5 microl saline) reduced, in a dose dependent manner, the endotoxin-induced hyperalgesia and exerted differential effects on the up-regulated levels of cytokines in different areas of the brain. The results provide behavioral and immunochemical characterization of a rat model for intracerebral inflammation and indicates a neuroprotective role for thymulin in the CNS.
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Abnormal corticosteroid release is extensively associated with mood disorders. This association may result from the toxic actions of endogenous corticosteroids which can induce apoptosis of hippocampal neurons. Similarly, dexamethasone, a synthetic corticosteroid, can induce lethal and sublethal damage to rat hippocampal and striatal neurons and can result in steroid-induced psychoses in humans. ⋯ Pretreatment with oestrogen substantially attenuated the dexamethasone-induced neuronal damage. This oestrogen-induced neuronal protection was in turn virtually eliminated by giving an initial injection of tamoxifen. These results suggest, therefore, that oestrogens can protect from corticosteroid-induced neuronal damage via an oestrogen receptor-mediated process.
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Zinc plays an important role in synaptic signaling in the mammalian cerebral cortex. Zinc is sequestered into presynaptic vesicles of subpopulations of glutamatergic neurons and is released by depolarization, in a calcium-dependent manner. As the majority of mechanisms that have been suggested to participate in experience-dependent alterations in synaptic strength in the cerebral cortex implicate signaling by glutamate, it stands to reason that zincergic signaling might also be crucial. ⋯ In all age groups, levels of zinc staining returned to baseline by 21 days after whisker plucking. However, only in juvenile and adult mice did we observe that the level of zinc staining in deprived barrel hollows, was correlated with the length of whiskers as they regrew. Our data suggest that alterations in the regulation of synaptic zinc may be involved with decrements of synaptic plasticity that accompany senescence.
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This study examined the role of spinal GABAergic, serotoninergic and alpha(2) adrenergic receptors in the antinociception produced by the microinjection of equi-antinociceptive doses of selective opioid receptor agonists in the nucleus raphe magnus (NRM) or the nucleus reticularis gigantocellularis pars alpha (NGCpalpha) of the rat. Rats were pretreated with intrathecal administration of either the GABA(A) receptor antagonist bicuculline, the GABA(B) receptor antagonist CGP35348, the serotonin(1/2) receptor antagonist methysergide, the alpha(2) adrenergic receptor antagonist yohimbine or saline. Ten minutes later, either the delta(1) opioid receptor agonist [D-Pen(2,5)]enkephalin (DPDPE), delta(2) opioid receptor agonist [D-Ala(2),Glu(4)]deltorphin (DELT) or mu opioid receptor agonist [D-Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) was microinjected into the NRM, NGCpalpha or sites in the medulla outside these two regions. ⋯ Intrathecal pretreatment with methysergide or bicuculline did not antagonize the antinociception produced by microinjection of DELT into either the NRM or the NGCpalpha. The increase in tail-flick latency produced by microinjection of DAMGO in the NRM was antagonized by intrathecal pretreatment with methysergide or CGP35348, but not by bicuculline or yohimbine. Taken together, these results support the hypothesis that the antinociception produced by activation of delta(1), delta(2) or mu opioid receptors in the rostral ventromedial medulla is mediated by different neural substrates.