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Activation of orexin system facilitates anesthesia emergence and pain control.
Zhou, Wei; Cheung, Kevin; Kyu, Steven; Wang, Lynn; Guan, Zhonghui; Kurien, Philip A; Bickler, Philip E; Jan, Lily Y.
Afiliación
  • Zhou W; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143; Wei.Zhou@ucsf.edu Lily.Jan@ucsf.edu.
  • Cheung K; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
  • Kyu S; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
  • Wang L; Department of Physiology, University of California, San Francisco, CA 94158.
  • Guan Z; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
  • Kurien PA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
  • Bickler PE; Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143.
  • Jan LY; Department of Physiology, University of California, San Francisco, CA 94158; Wei.Zhou@ucsf.edu Lily.Jan@ucsf.edu.
Proc Natl Acad Sci U S A ; 115(45): E10740-E10747, 2018 11 06.
Article en En | MEDLINE | ID: mdl-30348769
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Periodo de Recuperación de la Anestesia / Receptores de Orexina / Orexinas / Hipotálamo / Neuronas Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Periodo de Recuperación de la Anestesia / Receptores de Orexina / Orexinas / Hipotálamo / Neuronas Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos