At present, the mechanisms by which general anesthetics causing loss of consciousness remain unclear. The central medial thalamic nucleus (CMT) is a rarely studied component of the midline thalamic complex, which is deemed to be a part of the nonspecific arousal system. Although the CMT participates in modulating arousal and receives excitatory noradrenergic projections from locus coeruleus, it remains unknown whether the noradrenergic pathway in the CMT takes part in modulating the arousal system. Therefore, we hypothesized that noradrenergic transmission in the CMT is involved in modulating induction and emergence of propofol anesthesia. First, we infused norepinephrine (NE) into the CMT to observe the role of CMT noradrenergic pathway in modulating the anesthetic state induced by propofol. The results showed that microinjection of NE into the CMT accelerated emergence from propofol anesthesia, but had no impact on the induction of or sensitivity to propofol anesthesia in rats. In addition, infusion of NE into the CMT caused electroencephalography changes in the prefrontal cortex and the anterior cingulate cortex. Finally, we used a whole-cell patch clamp to examine the effects of NE on neuronal excitability and GABAergic transmission in the CMT. In the CMT slices, propofol suppressed neuronal excitability and enhanced GABAergic transmission, while application of NE partly reversed these effects. These findings support the hypothesis that the CMT noradrenergic pathway plays an important role in modulating the emergence from general anesthesia.

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Objectives:To identify the changes of local coherence and intrinsic brain activity in resting-state idiopathic trigeminal neuralgia (ITN) patients by using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) analysis.Methods:ReHo and fALFF were analyzed in 23 ITN patients and 23 age-matched and sex-matched pain-free controls to detect the functional abnormality in the brains of ITN patients. Correlations between ReHo and fALFF were analyses. ITN pain intensity were also assessed in the ITN group.Results:Compared with pain-free controls, ITN patients exhibited significantly abnormal ReHo and fALFF in several brain regions, including the cerebellum, cingulate cortex, temporal lobe, putamen, occipital lobe, limbic lobe, precuneus, insula, medial, and superior frontal gyrus compared with healthy controls. Correlation analysis showed that ReHo values of several altered brain areas positively correlated with visual analog scale values. But no correlation was found between fALFF and visual analog scale.Discussion:Our results showed that ITN patients exhibited significantly abnormal spontaneous brain activity in several brain regions that are involved in pain modulation and perception. The present study reflects the maladaptive process of daily pain attacks and may enhance the understanding of how chronic pain affects local intrinsic brain activity.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Electroencephalogram monitoring during propofol (PRO) anesthesia typically features low‐frequency oscillations, which may be involved with thalamic reticular nucleus (TRN) modulation. TRN receives noradrenergic inputs from the locus coeruleus (LC). We hypothesized that specific noradrenergic connections in the TRN may contribute to the emergence from PRO anesthesia. Intranuclei norepinephrine (NE) injections (n = 10) and designer receptors exclusively activated by designer drugs (DREADDs) (n = 10) were used to investigate the role of noradrenergic inputs from the LC to the TRN during PRO anesthesia. Whole‐cell recording in acute brain slice preparations was used to identify the type of adrenoceptor that regulates noradrenergic innervation in the TRN. An intracerebral injection of NE into the TRN delays arousal in mice recovering from PRO anesthesia (means ± sd; 486.6 ± 57.32 s for the NE injection group vs. 422.4 ± 48.19 s for the control group; P = 0.0143) and increases the cortical‐δ (0.1–4 Hz, 25.4 ± 2.9 for the NE injection group vs. 21.0 ± 1.7 for the control group; P = 0.0094) oscillation. An intra‐TRN injection of NE also decreased the EC50 of PRO‐induced unconsciousness (57.05 ± 1.78 mg/kg for the NE injection group vs. 72.44 ± 3.23 mg/kg for the control group; P = 0.0096). Moreover, the activation of LC‐noradrenergic nerve terminals in the TRN using DREADDs increased the recovery time [466.1 ± 44.57 s for the clozapine N‐oxide (CNO) injection group vs. 426.1 ± 38.75 s for the control group; P = 0.0033], decreased the EC50 of PRO‐induced unconsciousness (64.77 ± 3.40 mg/kg for the CNO injection group vs. 74.00 ± 2.08 mg/kg for the control group; P = 0.0081), and increased the cortical‐δ oscillation during PRO anesthesia (23.29 ± 2.58 for the CNO injection group vs. 19.56 ± 1.9 for the control group; P = 0.0213). In addition, whole‐cell recording revealed that NE augmented the inhibitory postsynaptic currents in the TRN neurons via the α1‐adrenoceptor. Our data indicated that enhanced NE signaling at the noradrenergic terminals of the LC‐TRN projection delays arousal from general anesthesia, which is likely mediated by the α1‐adrenoceptor activation. Our findings open a door for further understanding of the functions of various LC targets in both anesthesia and arousal.—Zhang, Y., Fu, B., Liu, C., Yu, S., Luo, T., Zhang, L., Zhou, W., Yu, T. Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice. FASEB J. 33, 7252–7260 (2019). http://www.fasebj.org

Propofol can promote presynaptic GABA release, inhibit presynaptic glutamate release and increase postsynaptic GABA receptor sensitivity, which eventually inhibits the activity of vPAG DA neurons and thereby influences the state of consciousness.

Although accumulative evidence indicates that the thalamocortical system is an important target for general anesthetics, the underlying mechanisms of anesthetic action on thalamocortical neurotransmission are not fully understood. The aim of the study is to explore the action of etomidate on glutamatergic and GABAergic transmission in rat thalamocortical slices by using whole cell patch-clamp recording. We found that etomidate mainly prolonged the decay time of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs), without changing the frequency. Furthermore, etomidate not only prolonged the decay time of miniature inhibitory postsynaptic currents (mIPSCs) but also increased the amplitude. On the other hand, etomidate significantly decreased the frequency of spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs), without altering the amplitude or decay time in the absence of bicuculline. When GABA receptors were blocked using bicuculline, the effects of etomidate on sEPSCs were mostly eliminated. These results suggest that etomidate enhances GABAergic transmission mainly through postsynaptic mechanism in thalamocortical neuronal network. Etomidate attenuates glutamatergic transmission predominantly through presynaptic action and requires presynaptic GABA receptors involvement.