Caudal Nucleus Tractus Solitarius (NTS)在針灸改變睡眠所扮演的角色

Abstract

Electroacupuncture (EA) possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17) acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhanced non-rapid eye movement (NREM) sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS). In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement (REM) sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the μ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of δ-receptor antagonist, natrindole, and the κ-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the μ-opioid receptors. One ascending projection is from NTS to the ventromedial nucleus (VM) of the thalamus (the NTS-VM pathway). Wakefulness is accompanied by synaptic potentiation in the cortical circuits, whereas slow wave activity (SWA) during slow wave sleep (SWS) promotes a generalized depression or downscaling of synaptic strength. The VM receives opioidergic inputs from NTS and the activation of opioid receptors hyperpolarize neurons of VM. Accordingly, 10 Hz EA may increase synaptic activity of NTS and subsequently hyperpolarize and downscale the synaptic strength in the VM of thalamus by inhibitory afferents, which lead to the enhancement of SWS. Enhancement of excitatory synapses in NTS and inhibitory synapses in VM may respectively contribute to the up-regulation of synaptic strength in NTS and downscaling of synaptic strength in the VM after 10 Hz EA. Our results demonstrated that the synaptic density was increased in both NTS and VM after rats received 10 Hz EA stimuli, while the enhanced synaptic length was only observed in the NTS, suggesting that 10 Hz EA altered excitatory synaptic strength of NTS and inhibitory synaptic strength of VM by changing the synaptic morphology. Studies have shown that different kinds of endogenous opiate peptides and receptors may mediate the consequences of EA with different frequencies. Herein we further elucidated that high frequency (100 Hz) EA of Anmian enhanced NREM sleep during the dark period, but exhibited no direct effect on REM sleep. High frequency EA-induced NREM sleep enhancement was dose-dependently blocked by microinjection of naloxone or κ-receptor antagonist (nor-binaltrophimine) into the caudal NTS, but was affected neither by μ-(naloxonazine) nor δ-receptor antagonists (natrindole), suggesting the role of NTS κ-receptors in the enhancement of high frequency EA-induced NREM sleep. Current and previous results have combined to depict the opioid mechanisms of EA-induced sleep.