Intranasal Dexmedetomidine for the Treatment of Pre-operative Anxiety and Insomnia: A Prospective, Randomized, Controlled, and Clinical Trial

Zeng, Wen; Chen, Li; Liu, Xin; Deng, Xujiang; Huang, Kuan; Zhong, Maolin; Zhou, Shui‐Hong; Zhan, Lifang; Yu-lu, Jiang; Li, Weidong

doi:10.3389/fpsyt.2022.816893

Cited by 4 publications

(2 citation statements)

References 42 publications

(55 reference statements)

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“…For example, in humans, sub-anesthesia levels of ketamine, an NMDA receptor antagonist, produces robust, quick-onset, and long-lasting anxiolysis on patients with refractory anxiety disorders or social anxiety disorders [8][9][10] . Dexmedetomidine, an a2adrenergic receptor agonist, alleviated anxiety-like behaviors in a rodent model of posttraumatic stress disorder (PTSD) 11 and in nerve ligation-induced chronic pain 12 , and has long been used to provide peri-operative anxiolysis in animals and human patients [13][14][15] . Sevoflurane, a GABA-receptor potentiator, also reversed the long-term anxiety-like behaviors caused by a single episode of formalin induced inflammatory pain in rodents 16 .…”

Section: Introductionmentioning

confidence: 99%

General Anesthesia Activates a Central Anxiolytic Center in the BNST

Lu,

Choi,

Park

et al. 2023

Preprint

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SUMMARYLow doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects. How these different drugs exert these anxiolytic effects is not well understood. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that is activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). A majority of ovBNSTGAneurons express neurotensin receptor 1 (Ntsr1) and innervate brain regions known to regulate anxiety and stress responses. Optogenetic activation ovBNSTGAor ovBNSTNtsr1neurons significantly attenuated anxiety-like behaviors in both naïve animals and mice with inflammatory pain, while inhibition of these cells increased anxiety. Notably, activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety through modulation of the autonomic nervous system. Our study identifies ovBNSTGA/ovBNSTNtsr1neurons as one of the brain’s endogenous anxiolytic centers and a potential therapeutic target for treating anxiety-related disorders.HIGHLIGHTSGeneral anesthetics and anxiolytics activate a population of neurons in the ovBNSTAnesthesia-activated ovBNST neurons bidirectionally modulate anxiety-like behaviorMost anesthesia-activated ovBNST neurons express neurotensin receptor 1ovBNSTNtsr1neuron activation shifts autonomic responses to an anxiolytic state

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Section: Introductionmentioning

confidence: 99%

General Anesthesia Activates a Central Anxiolytic Center in the BNST

Lu,

Choi,

Park

et al. 2023

Preprint

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“…Dex has been shown to have neuroprotective effects both in vivo and in vitro [13][14][15] and these effects are increasingly considered to have clinical implications. Because Dex sedation is closer to the characteristics of natural sleep [16], Dex is often used to improve the sleep quality of perioperative patients and critically ill patients [17][18][19][20][21]. Previous studies have shown that dexmedetomidine can improve the emotional behavior [22] and cognitive dysfunction [23] caused by sleep deprivation but the mechanism is not clear.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Improves Anxiety-like Behaviors in Sleep-Deprived Mice by Inhibiting the p38/MSK1/NFκB Pathway and Reducing Inflammation and Oxidative Stress

Zhang

Deng

et al. 2023

Brain Sciences

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(1) Background: Sleep deprivation (SD) triggers a range of neuroinflammatory responses. Dexmedetomidine can improve sleep deprivation-induced anxiety by reducing neuroinflammatory response but the mechanism is unclear; (2) Methods: The sleep deprivation model was established by using an interference rod device. An open field test and an elevated plus maze test were used to detect the emotional behavior of mice. Mouse cortical tissues were subjected to RNA sequence (RNA-seq) analysis. Western blotting and immunofluorescence were used to detect the expression of p38/p-p38, MSK1/p-MSK1, and NFκBp65/p- NFκBp65. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA); (3) Results: SD triggered anxiety-like behaviors in mice and was closely associated with inflammatory responses and the MAPK pathway (as demonstrated by transcriptome analysis). SD led to increased expression levels of p-p38, p-MSK1, and p-NFκB. P38 inhibitor SB203580 was used to confirm the important role of the p38/MSK1/NFκB pathway in SD-induced neuroinflammation. Dexmedetomidine (Dex) effectively improves emotional behavior in sleep-deprived mice by attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex, mainly by inhibiting the activation of the p38/MSK1/NFκB pathway; (4) Conclusions: Dex inhibits the activation of the p38/MSK1/NFκB pathway, thus attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex of mice.

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Preoperative anxiety and postoperative adverse events: a narrative overview

Zhu

2023

APS

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Patients awaiting surgical procedures often experience obvious anxiety due to discomfort and uncertain events, which is one of the most common clinical manifestations in perioperative patients. Numerous studies have confirmed that preoperative anxiety is closely related to the occurrence of postoperative adverse events, such as insomnia, pain, nausea and vomiting and neurocognitive dysfunction. Appropriate intervention or treatment for preoperative anxiety may contribute to reducing the incidence of postoperative adverse events. Although people have long known about the negative effects of preoperative anxiety and have taken certain measures, the underlying mechanism has yet to be fully elucidated. In this paper, we focus on several typical postoperative adverse events that are, particularly concerning to anesthesiologists, review their relationships with preoperative anxiety, describe the intervention strategies and provide a certain summary and outlook.

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Intranasal Dexmedetomidine for the Treatment of Pre-operative Anxiety and Insomnia: A Prospective, Randomized, Controlled, and Clinical Trial

Cited by 4 publications

References 42 publications

General Anesthesia Activates a Central Anxiolytic Center in the BNST

General Anesthesia Activates a Central Anxiolytic Center in the BNST

Dexmedetomidine Improves Anxiety-like Behaviors in Sleep-Deprived Mice by Inhibiting the p38/MSK1/NFκB Pathway and Reducing Inflammation and Oxidative Stress

Preoperative anxiety and postoperative adverse events: a narrative overview

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