At some point, everyone has suffered from nausea. More than half of all pregnant women, surgical patients and cancer patients experience nausea and vomiting, and up to a quarter of all people struggle with chronic nausea. And, of course, millions are affected every year by the nausea that comes with nasty stomach bugs such as the norovirus.
Yet we still have few effective treatments for nausea. Over-the-counter medications such as Dramamine cause sedation, and the most effective prescription drugs, such as Zofran, diminish nausea in fewer than half of patients, experts say.
“Why don’t we have more drugs to help this?” asks Kenneth L. Koch, a professor of gastroenterology at Wake Forest School of Medicine in Winston-Salem, N.C. “A cold washcloth is about what we have.”
“Nausea doesn’t get the respect it should,” Koch adds. “People say, ‘If you don’t like the nausea, then get off the merry-go-round.’” But this isn’t an option for people with the chronic and severe nausea that comes with conditions such as hyperemesis gravidarum, or HG, a brutal form of nausea that affects nearly 10 percent of pregnant women (including the Duchess of Cambridge, formerly Kate Middleton) and can lead to dehydration, malnutrition and hospitalization.
Disrupted stomach rhythms
Koch is working to understand nausea and develop more effective treatments by tracking the electrical activity of the stomachs of nauseated volunteers.
The stomach has an electrical rhythm to control its churning action, which runs at three cycles per minute. In his tests, Koch found that these rhythms were disrupted, running either too fast or too slow. He’d like to find a way to use electrical stimulation or drugs to restore proper rhythms to upset stomachs.
Neurogastroenterologist Braden Kuo and neuroscientist Vitaly Napadow, both at Massachusetts General Hospital in Boston, are taking another approach to the mystery of nausea by investigating motion-induced nausea. With some fancy engineering and a movie projection of fast-moving vertical lines, they built an MRI scanner that simulates a spinning room.
As volunteers lie inside the machine, the team tracks which areas of their brain grow active as their nausea ratchets up. The participants push a button that records their rating of the nausea’s intensity and allows them to cry “Uncle!” before puking.
Kuo and Napadow found that nausea activates brain areas involved in pain and fear and areas that deal with emotions and decision-making. Those last areas might represent a cognitive evaluation of the sensation, Napadow says, “as in ‘How long can I take it?’” Also, Kuo says the lit-up brain areas suggest that certain non-narcotic pain medications or antidepressants might help control nausea. It’s an important first peek into the brain during nausea, and the MRI setup might help test new types of drugs.
Charles Horn, a neuroscientist at the University of Pittsburgh Cancer Institute, is studying the musk shrew, which, unlike lab rats and mice, does vomit. Horn exposes the shrews to chemotherapy drugs or anesthesia medications that cause severe nausea in humans.
But since Horn cannot ask the shrews to rate their nausea, he has found others ways to track it. When nauseated, the shrews avoid a saccharin treat associated with the nausea and stop rearing up on their hind legs. It’s a movement akin to curling up on the sofa, he says. By tracking molecular markers in the shrew’s brain, Horn has identified signals that travel from a nauseated shrew’s gut to activate areas in its brain stem and cause vomiting.
Sorting out which molecules control that gut-to-brain signaling is the first step in designing new drugs to block them, he says. But such drugs are probably more than a decade away.
Nausea during pregnancy
Marlena Fejzo, a geneticist at UCLA, is focusing on the role of genetics in HG. She thinks that some women may have more trouble than others in breaking down so-called pregnancy hormones (hCG and estrogen) and clearing them from the bloodstream, so that the circulating byproducts become toxic.
Fejzo has shown that HG tracks with a woman’s genetics: Having a sister who had HG means that a woman has 17 times more risk of having HG herself.
Fejzo has recruited more than 1,000 women with HG and more than 700 friends of theirs who had pregnancies without nausea; they will all be invited to send her saliva DNA samples that she will mine for genetic differences. She has also tested five families of women whose mothers and sisters had HG, to look at their whole genome for clues. While her results are not yet published, she says they support her idea that women who have a harder time breaking down hormones may be more likely than others to experience HG.
Although vomiting serves to quickly rid the stomach of toxins caused by food poisoning and stomach bugs, Fejzo, Koch and other researchers would like to erase the debilitating nausea and vomiting that apparently serve no good purpose in most other people.
“If we could understand and treat nausea,” says Koch, “then there would be no vomiting.”