Authors: Tong L et al.
Anesthesiology 144(4):853–870, April 2026
Summary:
This mechanistic study investigates the role of glutamatergic neurons in the dorsomedial periaqueductal gray (dmPAG) as a potential common neural pathway regulating anesthesia and emergence. The periaqueductal gray has long been recognized for its role in pain and defensive behaviors, but its contribution to anesthesia–arousal transitions is increasingly being explored.
Using mouse models, the researchers demonstrated that dmPAG glutamatergic neuronal activity is consistently suppressed during general anesthesia—across multiple agents including sevoflurane, propofol, ketamine, and dexmedetomidine—and reactivates during emergence. This suggests a shared neural mechanism across anesthetic classes.
Through optogenetic and chemogenetic manipulation, the study showed that activating these neurons delayed induction of anesthesia while significantly accelerating emergence. In contrast, inhibiting these neurons deepened anesthesia and prolonged recovery. EEG findings supported these results, with activation of dmPAG neurons producing wake-like brain activity even during ongoing anesthetic exposure.
These findings indicate that dmPAG glutamatergic neurons play a central role in modulating consciousness under anesthesia and may serve as a key “switch” controlling transitions between anesthetized and awake states. The consistency of these effects across multiple anesthetic agents strengthens the argument for a shared neural substrate underlying general anesthesia.
While these results are limited to animal models, they provide important insight into the neurobiology of anesthesia and suggest potential future targets for improving emergence and managing delayed recovery.
Key Points:
- dmPAG glutamatergic neurons are suppressed during anesthesia and activated during emergence
- Activation delays induction but accelerates recovery from anesthesia
- Inhibition deepens anesthesia and prolongs emergence
- Effects are consistent across multiple anesthetic agents
- Suggests a common neural pathway regulating consciousness under anesthesia
What You Should Know:
This is getting at the “switch” for anesthesia. Instead of thinking about drugs alone, this points to specific brain circuits controlling unconsciousness and wake-up. If this translates to humans, it could change how we manage emergence, delayed wake-ups, and even depth of anesthesia.
We would like to thank Anesthesiology for allowing us to summarize and share this article.