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Activation of orexin system facilitates anesthesia emergence and pain control.

ABSTRACT: Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.

SUBMITTER: Zhou W

PROVIDER: S-EPMC6233126 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Activation of orexin system facilitates anesthesia emergence and pain control.

Zhou Wei W Cheung Kevin K Kyu Steven S Wang Lynn L Guan Zhonghui Z Kurien Philip A PA Bickler Philip E PE Jan Lily Y LY

Proceedings of the National Academy of Sciences of the United States of America 20181022 45

Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by des ...[more]

PMID: 30348769

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Project description:BackgroundEndotracheal extubation under deep anesthesia (deep extubation) has been proved to present stable hemodynamics and steady intracranial pressure during emergence from anesthesia in patients undergoing craniotomy. This study aims to examine, in comparison with deep extubation, if a laryngeal mask airway (LMA) could provide a safer and smoother emergence from anesthesia in patients undergoing craniotomy.MethodsThis prospective randomized controlled study was conducted on patients undergoing elective craniotomy for brain tumors. After the complement of the surgical procedure, the patients had anesthesia maintained with end-tidal sevoflurane concentration 2.5% and also fully regained muscle power (Time Zero), they were randomly assigned to ETT Group (n = 29) for deep extubation or to LMA Group (n = 29), where the endotracheal tube was replaced by a laryngeal mask airway. The primary outcomes were respiratory complications, airway interventions and hemodynamic changes through emergence from anesthesia till 30 min following Time Zero. The secondary outcomes were re-operation incidence in 24 h, stay time in the intensive care unit and postoperative hospital days.ResultsAt 5 min before Time Zero either oxygen partial pressures (PaO2) or carbon dioxide partial pressures (PaCO2) between the two groups were comparable. No significant PaCO2 change was noted in both groups in 5 min after Time Zero, yet there was a remarkably lower PaO2 in ETT Group at that time point, 188.9 (± 71.1) in ETT Group vs 264.4 (± 85.4) in LMA Group. In ETT Group, coughs and snores were considerably more frequent, and thus more interventions were needed to maintain adequate respiration. From Time Zero on, blood pressures (systolic, diastolic and mean) and heart rates in ETT Group were generally higher than those in LMA Group, but the differences were insignificant at all time points except heart rate at 10 min after Time Zero. The secondary outcomes between the two groups were similar.ConclusionsCompared with deep extubation, a LMA, as a temporary airway replacement, facilitates a safer and smoother emergence from anesthesia for patients undergoing craniotomy, in terms of better oxygen saturation, fewer respiratory complications and fewer airway interventions.Trial registrationThe study was conducted after receiving approval from Institutional Review Board of Chang Gung Memorial Hospital, Linkou Branch, Taiwan (registration number 202102115A3; January 27, 2022), and the clinicaltrials.gov (NCT05253404) on 23 February 2022.

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Activation of orexin system facilitates anesthesia emergence and pain control.

Publications

Activation of orexin system facilitates anesthesia emergence and pain control.

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