All roads lead to nausea
Nausea is not a disease, but a collection of symptoms that can arise from a variety of causes. Symptoms such as dizziness, stomach pain, lethargy, lack of appetite, sweating, cramps around the internal organs – and vomiting.
However, in some people, vomiting persists, and that can be even more unpleasant. That’s because your brain releases endorphins after you throw up. Endorphins make you feel happy and good, so throwing up often feels like a huge relief. And without vomiting, the endorphins don’t do their job.
Several factors can trigger nausea, and since each affects the body differently, the route to nausea is not always the same.
Motion sickness and vertigo affect the brain by disrupting the optic nerve and balance, while overeating can cause nausea by affecting receptors in the stomach.
Why the body reacts to these stimuli with nausea is not always clear. But sometimes the effect is actually beneficial. By consciously throwing up when you feel nauseous after drinking too much alcohol or eating spoiled food, the body can limit the damage. When you vomit, you get rid of residual toxins in the stomach before they end up in the blood.
This mechanism is probably also the reason why some medicines, for example for the treatment of cancer or diabetes, can cause nausea – the body sees the medicines as toxins that need to be eliminated.
Because of the multitude of causes of nausea, researchers have always had a hard time pinpointing its source. But a certain brain area has been under suspicion for a long time.
Brain makes you vomit
As early as the 1950s, the brain center area postrema was discovered to be associated with nausea. And in the 1980s, experiments showed that mice became nauseated when this center was electrically stimulated. Conversely, damage to the center prevented the mice from becoming nauseous.
Today scientists know that the area postrema causes nausea when the center picks up certain toxins or hormones from the blood. It is responsible for nausea during pregnancy, after a hangover and from taking certain medications – but not for motion sickness, which occurs elsewhere in the brain.
The ability of the brain center to respond to substances in the blood is due to its position. It is located in what is called the fourth ventricle of the brainstem, outside the part of the brain where the blood vessels are surrounded by the blood-brain barrier. This barrier keeps harmful substances away from the brain cells – but the substances can still reach the area postrema.
In the brain center, the drugs activate the chemoreceptor trigger zone (CTZ), which contains a variety of receptors that are sensitive to the drugs. The CTZ then sends a message to the rest of the brain and body, triggering nausea and vomiting.
Several anti-nausea medications work by blocking receptors in the CTZ. The problem is that there are many receptors, and the drug doesn’t always hit the receptor that makes you sick. In addition, the receptors are located elsewhere in the body, where they serve important purposes unrelated to nausea, and so the drug can cause unpleasant side effects.
New medicines are therefore urgently needed. Fortunately, researchers have uncovered a flaw in the biology of nausea that could be crucial in the fight against it.
New technique reveals important detail
The nausea center, the small area postrema, is located deep in the brain, making it difficult to study. However, in 2021, a group of researchers from Harvard Medical School learned a lot about the clump of brain cells – thanks to a groundbreaking new method.
The researchers removed the brain center of mice and examined it using a technique that single-nucleus RNA sequencing is called.
The RNA is a kind of copy of the active genes in the cell nucleus and functions as a blueprint for the proteins of the cell. By reading the RNA, researchers can see which proteins the cell is building. The proteins are the workers of the cell, and their composition reveals what the cell can and does.
The study showed that the area postrema contains two very different types of nerve cells.
One group of cells initiates the nausea, the other group inhibits the first and thus prevents the discomfort.
Following that discovery, the Harvard researchers conducted another trial in 2022 – this time with a drug that may prove to have great potential.
New medicines on the way
The researchers first gave a group of test mice water containing a substance that induces nausea. This unpleasant feeling caused the mice to avoid the water.
Another group of mice was given water with the same substance, and also with the hormone GIP, which activates the nausea-inhibiting nerve cells.
The experiment was a success. GIP counteracted the effect of the nauseating substance in the water, and the second group of mice happily drank the water – without any sign of nausea.
The results pave the way for a new strategy in the fight against nausea. Previously, researchers mainly tried drugs that block specific receptors on the nerve cells. But each receptor is involved in only a few types of nausea, so the drugs don’t work for many patients.
By now stimulating the nerve cells that inhibit nausea, doctors only need one drug for nausea after a hangover, during pregnancy and from chemotherapy, among other things.
The only type of nausea that the Harvard researchers’ weapon doesn’t help with is motion sickness. But who knows, thanks to their research into the individual nerve cells, they may soon also be able to uncover the secrets of motion sickness – and learn how all types of nausea are interrelated in the brain.
When that happens, they can finally develop a truly universal remedy, for cancer patients up to and including people with motion sickness.