General anesthesia diverts sleep circuits to knock you out

The discovery of general anesthesia 170 years ago was a medical miracle, allowing millions of patients to undergo invasive and vital pain-free surgery. Yet, despite decades of research, scientists still do not understand why general anesthesia works.

Now scientists think they have discovered part of the answer. In a study published online April 18 in neuron, a team from Duke University has discovered that several different general anesthesia medications are killing you by diverting the neural circuit that makes you sleep.

The researchers traced these neural circuits to a small group of cells located at the base of the brain, responsible for producing hormones to regulate bodily functions, mood and sleep. This discovery is one of the first to suggest a role for hormones in maintaining the state of general anesthesia and provides valuable information for the creation of new drugs that could lull patients with less pain. Side effects.

Since the first patient was subjected to general anesthesia in 1846, scientists are trying to understand how it works. The prevailing theory has been that many of these drugs impede normal brain activities, resulting in an inability to move or feel pain. Similar theories revolved around sleep, from brotherhood to general anesthesia. However, research conducted over the past decade has shown that sleep is a more active process than previously recognized, with whole sets of neurons functioning as you capture your Z.

Fan Wang, Ph.D., a professor of neurobiology at the Duke University School of Medicine, and Li-Feng Jiang-Xie, a post-graduate student in his lab, wondered if the prevailing view of the university was the only one in the world. General anesthesia was also one way. "Maybe rather than simply inhibiting neurons, anesthetics could also activate certain neurons in the brain," Jiang-Xie said.

To test their new theory, Jiang-Xie and Luping Yin, Ph.D., a postdoctoral fellow at Wang Lab, submitted mice to general anesthesia with several different but commonly used drugs. They then used molecular markers to locate the neurons usually activated by anesthetics. They discovered a group of actively activating neurons buried in a tiny brain region called the supraoptic nucleus, known for its long projections that release large amounts of hormones such as vasopressin directly into the bloodstream.

"Most cells activated by anesthesia were a kind of hybrid cell connecting the nervous system and the endocrine system," Jiang-Xie said. "It took us by surprise and drove us into unexplored territory to understand the neural pathways of general anesthesia."

Next, the researchers exploited a sophisticated technique developed by the Wang laboratory to activate or deactivate this specialized group of cells containing chemicals or light. When they lit the cells of the mice, the animals stopped moving and fell into a deep sleep called slow wave sleep, usually associated with loss of consciousness.

Then the research team killed this group of cells. The mice continued to move, unable to fall asleep.

Finally, the researchers performed similar experiments on mice under general anesthesia. They found that artificial pre-activation of neuroendocrine cells forced mice to remain under general anesthesia for longer periods. Conversely, when they silenced these cells, mice woke up more easily from anesthesia.

This study also revealed a previously unexpected role of brain cells secreting hormones in the promotion of deep sleep.

"Many people, especially those with Alzheimer's disease, have trouble falling asleep, but current medications have troublesome side effects," said Yin. "If we can find ways to manipulate these neural circuits, perhaps by targeting hormones or small peptides, then that could lead to the development of better sleeping pills."