Medical professionals began using anesthesia over 150 years ago, with the first use at Massachusetts General Hospital, Boston during 1846. However, the doctors did not know how it worked to cause unconsciousness. This is one reason why so little has changed in anesthesia’s risks and effects. By studying how anesthesia works to make a person lose consciousness, researchers can learn more about the nature of sleep and why a person becomes unconsciousness. One of the most frequent explanations was called the lipid hypothesis, which indicated that anesthesia solubility in lipids was likely the trigger for the change. Why the body has this reaction is still being studied. Cell membranes contain lipids, but that doesn’t explain how it triggers unconsciousness.
Researchers at Scripps Research, San Diego, CA, proposed that the trigger was the disruption of lipid rafts, which disrupts how neurons fire, largely preventing the reaction from happening. They determined this by exposing cells to chloroform, which was once a type of anesthetic that medical professionals stopped using because it had too many potential negative side effects. Once the cells were in the chloroform, they were placed under a microscope and observed. Researchers saw that the natural lipid clusters were adjusting within the cell membranes. They were no longer tightly organized after the chloroform exposure. These clusters also began to release the contents that it stored, particularly the enzyme PLD2, which researchers colored with a florescent chemical to track it. The enzyme spread to lipid clusters, essentially freezing the neurons so that they stopped firing to signal other actions within the body. With the neurons unable to fire, the mind reacts by shutting down, and the person then loses consciousness. A similar experiment was then conducted on fruit flies, and found that without the enzyme (which they genetically removed), fruit flies required about twice as much chloroform before they lost consciousness.
While this does not provide a full explanation for how anesthesia works, it does provide at least one of the key reasons why anesthesia helps to render patients unconscious. It has also led to research into the role lipids play in a person falling sleep.
More details of the study are provided in Scientists Unravel the Mystery of Anesthesia.