Brain research
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Opioid effects are mediated by central and peripheral opioid receptors. Here we examine the relative contribution of each receptor population to antinociception elicited by systemically administered centrally penetrating opioids, and by loperamide (a peripherally restricted opioid). Nociception (abdominal writhes) was induced by intraperitoneally (i.p.) injected 0.6% acetic acid in mice. ⋯ NLXM. In conclusion, systemically administered centrally penetrating mu-, delta- and kappa-agonists produced a substantial part of antinociception through peripheral opioid receptors. Higher dose loperamide-induced antinociception involved also central opioid receptors.
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Although platelet-derived growth factor (PDGF)-BB activates PDGF receptor-beta (PDGFR-beta) and, in turn, inhibits the glutamate N-methyl-D-aspartate (NMDA) receptor function, whether PDGF-BB modulates the CNS function mediated by another glutamate receptors, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, remains poorly understood. Here we now report the inhibitory effect of PDGF-BB on the AMPA receptor function in the nucleus tractus solitarius (NTS) by using slice patch-clamp techniques. Excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of the tractus solitarius in mouse NTS second-order neurons. ⋯ The inhibitory effect of PDGF-BB on EPSCs was not observed in mutant mice with conditional deletion of the PDGFR-beta gene in neurons. Together, these studies suggest that the PDGF-B/PDGFR-beta axis inhibits the AMPA receptor-mediated synaptic transmission that comprises the major part of the primary afferent to the NTS second-order neuron. The detected inhibitory action may be involved in the CNS regulation of the respiratory response.
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The present study examined the anti-hypernociceptive effects of agmatine (AGM) in acute and chronic models of behavioural pain in mice. Agmatine (30 mg/kg, i.p. 30 min early), produced time-dependent inhibition of mechanical hypernociception induced by Complete Freund's Adjuvant (CFA) injected in the mice paw (inhibition of 52+/-7%) after 4 h. Given chronically (twice a day) during 10 days, AGM significantly reversed the mechanical hypernociception caused by CFA (inhibition of 43+/-6% to 67+/-5%). ⋯ Nevertheless, AGM failed to inhibit the paw oedema caused by CFA and the myeloperoxidase enzyme activity. Of note, AGM (10-100 mg/kg, i.p., 30 min before) also elicited a pronounced inhibition of the biting response induced by TNF-alpha and IL-1beta in mice, with mean ID(50) values of 61.3 mg/kg (47.7-78.6 mg/kg) and 30.4 mg/kg (18.6-49.8 mg/kg) and inhibitions of 75+/-5% and 66+/-6%, respectively. Together, present and previous findings show that AGM given systemically is effective in inhibiting mechanical and thermal hypernociception present in chronic inflammatory processes caused by CFA and also the neuropathic pain caused by PSNL.
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Modulation of long-interval intracortical inhibition and the silent period by voluntary contraction.
Transcranial magnetic stimulation was used to examine the effect of voluntary contraction on the magnitude of long-interval intracortical inhibition (LICI) and the duration of the silent period in intrinsic hand muscles. The magnitude of LICI acting on the first dorsal interosseus (FDI) measured with a paired-pulse protocol with an inter-pulse interval of 100 ms decreased with increasing tonic level of voluntary abduction force generated by the index finger. LICI in abductor pollicis brevis (APB) decreased from the condition in which the index finger was at rest to the conditions in which it was abducted, whereas LICI in abductor digiti minimi (ADM) was unaffected by the level of index finger abduction. ⋯ The duration of the silent period (SP) in FDI decreased with the level of voluntary index finger abduction and increased with eliciting stimulus intensity. Within-subject correlations showed that the effects of voluntary drive on SP duration and motor-evoked potential amplitude did not covary, implying an indirect effect of voluntary drive on SP duration. It is proposed that whereas voluntary drive directly reduces the magnitude of slow-acting inhibition acting on the active movement representations and near neighbors, sensory feedback from the contracting muscle acts to limit its time course.
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A mechanical insult to the brain drastically alters the microenvironment as specific cell types become reactive in an effort to sequester severely damaged tissue. Although injury-induced astrogliosis has been investigated, the relationship between well-defined biomechanical inputs and acute astrogliotic alterations is not well understood. We evaluated the effects of strain rate on cell death and astrogliosis using a three-dimensional (3-D) in vitro model of neurons and astrocytes within a bioactive matrix. ⋯ Moderate rate deformation increased cell density, GFAP reactivity, and hypertrophic process density. High rate deformation resulted in increased GFAP reactivity; however, other astrogliotic alterations were not observed at this time-point. These results demonstrate that the mode and degree of astrogliosis depend on rate of deformation, demonstrating astrogliotic augmentation at sub-lethal injury levels as well as levels inducing cell death.