[Show abstract][Hide abstract] ABSTRACT: The "gate control" theory suggests pain can be reduced by simultaneous activation of nerve fibres that conduct non-noxious stimuli. This study investigated the effects of vibration stimuli on pain experienced during local anaesthetic injections.
In a preliminary study, subjects were asked to rate anticipated and actual pain from regional anaesthetic injections in the oral cavity. A second study compared, within subjects, pain from injections with and without a simultaneous vibration stimulus. Both infiltration and block anaesthetic injection techniques were assessed. In each subject, two similar injections were given and with one, a vibration stimulus was randomly allocated. Injection pain was assessed by visual analogue scale and McGill pain descriptors.
Both infiltration and block injections were painful (mean anticipated intensity: 31.25, actual: 17.82 mm on 100 mm scale). Pain intensity with and without vibration was 12.9 mm (range 0-67) and 22.2 mm (range 0-83) respectively (p = 0.00005, paired T-test), and this effect was seen with both infiltration (p = 0.032) and block anaesthetic (p = 0.0001) injection subgroups. Furthermore, compared to no vibration-stimulus injections, injections with vibration resulted in less pain descriptors chosen (p = 0.004), and the descriptors had a lower pain rating (p = 0.001).
The results suggest that vibration can be used to decrease pain during dental local anaesthetic administration.
Full-text · Article · Jul 2009 · Australian Dental Journal
[Show abstract][Hide abstract] ABSTRACT: The naturally occurring toxin rottlerin has been used by other laboratories as a specific inhibitor of protein kinase C-delta (PKC-delta) to obtain evidence that the activity-dependent distribution of glutamate transporter GLAST is regulated by PKC-delta mediated phosphorylation. Using immunofluorescence labelling for GLAST and deconvolution microscopy we have observed that D-aspartate-induced redistribution of GLAST towards the plasma membranes of cultured astrocytes was abolished by rottlerin. In brain tissue in vitro, rottlerin reduced apparent activity of (Na+, K+)-dependent ATPase (Na+, K+-ATPase) and increased oxygen consumption in accordance with its known activity as an uncoupler of oxidative phosphorylation ("metabolic poison"). Rottlerin also inhibited Na+, K+-ATPase in cultured astrocytes. As the glutamate transport critically depends on energy metabolism and on the activity of Na+, K+-ATPase in particular, we suggest that the metabolic toxicity of rottlerin and/or the decreased activity of the Na+, K+-ATPase could explain both the glutamate transport inhibition and altered GLAST distribution caused by rottlerin even without any involvement of PKC-delta-catalysed phosphorylation in the process.
Full-text · Article · Jul 2009 · Neurochemical Research
[Show abstract][Hide abstract] ABSTRACT: Hypothetical model based on deficient glutamatergic neurotransmission caused by hyperactive glutamate transport in astrocytes surrounding excitatory synapses in the prefrontal cortex is examined in relation to the aetiology of schizophrenia. The model is consistent with actions of neuroleptics, such as clozapine, in animal experiments and it is strongly supported by recent findings of increased expression of glutamate transporter GLT in prefrontal cortex of patients with schizophrenia. It is proposed that mechanisms regulating glutamate transport be investigated as potential targets for novel classes of neuroactive compounds with neuroleptic characteristics. Development of new efficient techniques designed specifically for the purpose of studying rapid activity-dependent translocation of glutamate transporters and associated molecules such as Na+, K+-ATPase is essential and should be encouraged.
No preview · Article · Jan 2006 · Journal of Biomedical Science
[Show abstract][Hide abstract] ABSTRACT: 1. It has been suggested that Na+/K+-ATPase and Na+-dependent glutamate transport (GluT) are tightly linked in brain tissue. In the present study, we have investigated Na+/K+-ATPase activity using Rb+ uptake by ‘minislices’ (prisms) of the cerebral cortex. This preparation preserves the morphology of neurons, synapses and astrocytes and is known to possess potent GluT that has been well characterized. Uptake of Rb+ was determined by estimating Rb+ in aqueous extracts of the minislices, using atomic absorption spectroscopy.
2. We determined the potencies of several known substrates/inhibitors of GluT, such as l-trans-pyrrolidine-2,4-dicarboxylate (LtPDC), dl-threo-3-benzyloxyaspartic acid, (2S,3S,4R)-2-(carboxycyclopropyl)-glycine (L-CCG III) and l-anti,endo-3,4-methanopyrrolidine dicarboxylic acid, as inhibitors of [3H]-l-glutamate uptake by cortical prisms. In addition, we established the susceptibility of GluT, measured as [3H]-l-glutamate uptake in brain cortical prisms, to the inhibition of Na+/K+-ATPase by ouabain. Then, we tested the hypothesis that the Na+/K+-ATPase (measured as Rb+ uptake) can respond to changes in the activity of GluT produced by using GluT substrates as GluT-specific pharmacological tools.
3. The Na+/K+-ATPase inhibitor ouabain completely blocked Rb+ uptake (IC50 = 17 µmol/L), but it also potently inhibited a fraction of GluT (approximately 50% of [3H]-l-glutamate uptake was eliminated; IC50 < 1 µmol/L).
4. None of the most commonly used GluT substrates and inhibitors, such as l-aspartate, d-aspartate, L-CCG III and LtPDC (all at 500 µmol/L), produced any significant changes in Rb+ uptake.
5. The N-methyl-d-aspartate (NMDA) receptor agonists (R,S)-(tetrazol-5-yl)-glycine and NMDA decreased Rb+ uptake in a manner compatible with their known neurotoxic actions.
6. None of the agonists or antagonists for any of the other major classes of glutamate receptors caused significant changes in Rb+ uptake.
7. We conclude that, even if a subpopulation of glutamate transporters in the rat cerebral cortex may be intimately linked to a fraction of Na+/K+-ATPase, it is not possible, under the present experimental conditions, to detect regulation of Na+/K+-ATPase by GluT.
Full-text · Article · Nov 2004 · Clinical and Experimental Pharmacology and Physiology