From the Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Anesth Analg. 2021 Sep 1;133(3):781-793. doi: 10.1213/ANE.0000000000005651.
Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia.
The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia.
Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia.
We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.
源自下丘脑外侧区（PeFLH）的神经肽食欲素促进异丙酚、异氟醚和七氟醚麻醉的恢复，而不影响诱导时间。然而，食欲素能系统在临床实践中广泛应用的地氟醚麻醉中是否也发挥类似作用，尚未研究。本研究旨在探讨食欲素能系统对地氟醚麻醉诱导意识状态的影响。
使用 c-Fos 染色观察 PeFLH 中食欲素能神经元在地氟醚麻醉下的活性变化及其传出投射区的活性变化。化学遗传学和光遗传学技术用于比较 PeFLH 食欲素能神经元对地氟醚和异氟醚麻醉诱导、苏醒和维持状态的影响。应用药理学、化学遗传学和光遗传学技术对地氟醚麻醉中下丘脑外侧区的食欲素能终末进行操作，以评估食欲素能回路对地氟醚麻醉的影响。
地氟醚麻醉抑制了 PeFLH 中的食欲素能神经元以及 PVT、基底前脑、中缝背核和腹侧被盖区的神经元活性，c-Fos 染色显示。PeFLH 食欲素能神经元的激活延长了诱导时间并加速了地氟醚麻醉的苏醒，但仅影响异氟醚麻醉的苏醒，化学遗传学和药理学技术证明。同时，在地氟醚麻醉下，光激活食欲素能神经元对爆发抑制比（BSR）表现出持久的抑制作用，而这种作用可能是由食欲素能 PeFLH-PVT 回路引起的。PVT 中的食欲素-2 受体（OX2R），而不是食欲素-1 受体（OX1R），受地氟醚抑制最明显，介导了地氟醚麻醉苏醒的促进作用。
我们首次发现 PeFLH 中的食欲素能神经元不仅可以影响异氟醚和地氟醚麻醉的维持和苏醒，还可以影响地氟醚麻醉的诱导。此外，这种特定的作用可能是由食欲素能 PeFLH-PVT 回路介导的，特别是 PVT 中的 OX2R。
