A medical miracle happened about 170 years ago when scientists discovered general anesthesia that enables millions of patients to undergo invasive, life-saving surgeries without pain. However, in spite of decades of research, scientists cannot understand why general anesthesia works.

In a new study published online in Neuron, scientists believe they have discovered the part of the answer. A team of researchers from a Duke University found that several different general anesthesia drugs knock out the patient by hijacking the neural circuitry that the person falls asleep.

They traced this neural circuitry to a tiny cluster of cells at the base of the brain responsible for churning out hormones to regulate bodily functions, moods, and sleep. The discovery is one of the first to indicate a role for the hormones in maintaining the state of general anesthesia and provides valuable insights for generating newer drugs that could put people to sleep with fewer side effects.

In 1846 when the first patient went under general anesthesia, scientists have been trying to figure out exactly how it works. The prevailing theory has been that many of these drugs tamp down the normal activities of the brain which results in the inability to move or feel pain. Also, the sister state to general anesthesia was similar theories that revolved around sleep. Studies over the last decades, however, have shown that sleep is a more active process than previously recognized, with entire sets of neurons clocking into work while you catch your Z's.

A professor of neurobiology at the Duke University School of Medicine, Fan Wang, Ph.D., and a graduate student in her laboratory, Li-Feng Jiang-Xie, wondered whether the predominant view of general anesthesia was also one-sided. Jiang-Xi said that rather than inhibiting neurons, anesthesia could also activate specific neurons in the brain.

She added that most of the anesthesia-activated cells were a kind of hybrid cells that connects the nervous system and the endocrine system. The discovery took them by surprise, and that led them into unexplored territory for understanding the neural pathways of general anesthesia.

Then, the scientists tapped a sophisticated method developed in the Wang lab to turn on or off this unique group of cells with chemicals or light. When they switched on the cells in mice, the animals stopped moving and fell into a deep slumber called slow-wave sleep, typically connected with unconsciousness.

The study finally performed the same experiments on mice under general anesthesia. The result indicated that artificially pre-activating the neuroendocrine cells made the mice stay under general anesthesia for extended periods. Conversely, when they silenced these cells, the mice woke up from anesthesia more easily.