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Catecholamine outflow from mouse and rat brain slice preparations evoked by nicotinic acetylcholine receptor activation and electrical field stimulation.

ABSTRACT: Mice with targeted deletions of neuronal nicotinic acetylcholine receptor (nAChR) subunit genes are valuable models to study nAChR function such as catecholamine outflow by presynaptic receptor activation. Contrary to the rat, our present knowledge on presynaptic nAChRs in mice primarily relies on observations made with synaptosomes. We have now used brain slices to investigate nicotine-induced catecholamine outflow in wild type (WT) and nAChR (beta2 and alpha5) knockout mice for a comparison with rat brain slice preparations.Brain slices from rat and mouse hippocampus, parieto-occipital neocortex, and corpus striatum were loaded with either [3H]-noradrenaline or [3H]-dopamine. We provoked catecholamine outflow by electrical field stimulation and nicotinic agonists.When set in relation to electrical field stimulation, nicotine-evoked catecholamine release was sizeable in the striatum but low in the neocortex of both rats and mice. [3H]-noradrenaline outflow was, on the other hand, substantial in the rat but low in the mouse hippocampus. About 10% (or less) of nicotine-induced catecholamine release persisted in the presence of tetrodotoxin in all our preparations.Targeted deletion of the beta2 subunit gene essentially abolished the effect of nicotine, indicating that this subunit is an essential constituent of nAChRs that indirectly (via action potentials) induce catecholamine release from hippocampal and striatal slices in mice. The impact of nAChRs in catecholaminergic projection areas differs between species and has thus to be considered when extrapolating results from animal models to human conditions.

SUBMITTER: Scholze P

PROVIDER: S-EPMC2013980 | biostudies-other | 2007 Jun

REPOSITORIES: biostudies-other

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Project description:ObjectiveFibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. This study was undertaken to investigate if using TENS during activity would improve movement-evoked pain and other patient-reported outcomes in women with FM.MethodsParticipants were randomly assigned to receive active TENS (n = 103), placebo TENS (n = 99), or no TENS (n = 99) and instructed to use it at home during activity 2 hours each day for 4 weeks. TENS was applied to the lumbar and cervicothoracic regions using a modulated frequency (2-125 Hz) at the highest tolerable intensity. Participants rated movement-evoked pain (primary outcome measure) and fatigue on an 11-point scale before and during application of TENS. The primary outcome measure and secondary patient-reported outcomes were assessed at baseline (time of randomization) and at 4 weeks.ResultsAfter 4 weeks, a greater reduction in movement-evoked pain was reported in the active TENS group versus the placebo TENS group (group mean difference -1.0 [95% confidence interval -1.8, -0.2]; P = 0.008) and versus the no TENS group (group mean difference -1.8 [95% confidence interval -2.6, -1.0]; P < 0.0001). A reduction in movement-evoked fatigue was also reported in the active TENS group versus the placebo TENS group (group mean difference -1.4 [95% confidence interval -2.4, -0.4]; P = 0.001) and versus the no TENS group (group mean difference -1.9 [95% confidence interval -2.9, -0.9]; P = <0.0001). A greater percentage of the patients in the active TENS group reported improvement on the global impression of change compared to the placebo TENS group (70% versus 31%; P < 0.0001) and the no TENS group (9%; P < 0.0001). There were no TENS-related serious adverse events, and <5% of participants experienced minor adverse events from TENS.ConclusionAmong women who had FM and were on a stable medication regimen, 4 weeks of active TENS use compared to placebo TENS or no TENS resulted in a significant improvement in movement-evoked pain and other clinical outcomes. Further research is needed to examine effectiveness in a real-world setting to establish the clinical importance of these findings.

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Catecholamine outflow from mouse and rat brain slice preparations evoked by nicotinic acetylcholine receptor activation and electrical field stimulation.

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