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Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10740-E10747. doi: 10.1073/pnas.1808622115. Epub 2018 Oct 22.

Activation of orexin system facilitates anesthesia emergence and pain control.

Author information

1
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143; Wei.Zhou@ucsf.edu Lily.Jan@ucsf.edu.
2
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
3
Department of Physiology, University of California, San Francisco, CA 94158.
4
Department of Physiology, University of California, San Francisco, CA 94158; Wei.Zhou@ucsf.edu Lily.Jan@ucsf.edu.
5
Howard Hughes Medical Institute, University of California, San Francisco, CA 94158.

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.

KEYWORDS:

DREADD; anesthesia; hypocretin; orexin; pain

PMID:
30348769
PMCID:
PMC6233126
DOI:
10.1073/pnas.1808622115
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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