Orexin-A hormone also affects emergence after anesthesia

A neuropeptide hormone called orexin-A—which plays an important role in regulating the normal sleep-wake cycle—also affects emergence (waking up) after anesthesia, reports an experimental study in the October issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Preliminary studies in rats suggest that the anesthetic drug propofol blocks the activity of brain cells which produce orexin-A, while administration of orexin-A hastens emergence from propofol anesthesia. The study was performed by Dr Hai-Long Dong and colleagues of Xijing Hospital, Xian, China.

Orexin-A Plays Role in Propofol Anesthesia and Emergence
The researchers designed a series of experiments in rats to study the role of orexins in the "anesthesia-arousal" cycle. They focused on the effects of propofol—a drug widely used not only for anesthesia but also as a sedative.

The orexins are a relatively recently discovered group of peptides expressed by neurons (nerve cells) in specific areas of the brain. "Accumulated evidence suggests that orexinergic [orexin-producing] neurons play a critical role in the promotion and the maintenance of wakefulness," the researchers write.

In the experiments, when rats were placed under propofol anesthesia, the activity of orexinergic neurons dropped sharply. When the rats emerged from anesthesia, orexinergic neuron activity returned to normal. Levels of orexin-A in the blood also decreased during propofol anesthesia. As in previous studies, the orexin-producing neurons were localized to a region called the basal forebrain.

In further experiments, anesthetized rats underwent injection of micro-level amounts of orexin- A into the basal forebrain. Within minutes, their brain electrical activity patterns changed from an "anesthetized" to an "arousal" pattern. Orexin-A injection also led to faster emergence from propofol anesthesia—about 40 percent faster than without orexin-A.

In contrast, a drug that blocked the orexin-A receptor delayed emergence from anesthesia. Neither orexin-A nor the receptor blocker affected the time to induce propofol anesthesia.

Recent studies have suggested that orexinergic neurons play an important role in the promotion and maintenance of wakefulness versus sleep in mammals. For example, drugs that block orexin impair the arousal process, leading to the sleep disorder narcolepsy. Previous reports have shown that other common anesthetics reduce the activity of orexinergic neurons.

The new study adds propofol to the list of anesthetics that act on orexinergic neurons in the basal forebrain. It also provides new evidence that orexin-A can facilitate emergence from anesthesia, while a drug that blocks orexin-A delays emergence.

"These findings indicate that the orexinergic signal pathway is involved in anesthesia-arousal regulation of propofol anesthesia," the researchers write. Future studies may help to clarify how orexinergic signals in the basal forebrain affect the process of emergence from anesthesia in human patients.

Source: Anesthesia & Analgesia

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