Understanding mechanism of sneeze may help limit spread of virus: study

CHICAGO - A team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex.

In the study, the researchers established a mouse model in an attempt to identify which nerve cells send signals that make mice sneeze. They exposed the mice to aerosolized droplets containing either histamine or capsaicin, a pungent compound made from chili peppers. Both elicited sneezes from the mice, as they do in people.

By examining nerve cells that already were known to react to capsaicin, the researchers identified a class of small neurons linked to sneezing that was caused by that substance. They then looked for molecules called neuropeptides that could transmit sneeze signals to those nerve cells, and found that a molecule called neuromedin B (NMB) was required for sneezing.

Conversely, when they eliminated the NMD-sensitive neurons in the part of the nervous system that evoked sneezes in the mice, they blocked the sneeze reflex. Those neurons all make a protein called the neuromedin B receptor. In mice without that receptor, sneezing again was greatly reduced.

"Interestingly, none of these sneeze-evoking neurons were housed in any of the known regions of the brainstem linked to breathing and respiration," said Qin Liu, a researcher in the university's Center for the Study of Itch and Sensory Disorders. "Although we found that sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found that the cells in those two regions were directly connected via their axons, the wiring of nerve cells."

The researchers also found they could stimulate the sneeze reflex by exposing part of the mouse brain to the NMB peptide. Further, the animals began to sneeze even though they had not been exposed to any capsaicin, histamine or other allergens.

Many viruses and other pathogens, including the majority of human rhinoviruses and coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, the coronavirus that causes COVID-19, are spread in part by aerosolized droplets. It may be possible to limit the spread of those pathogens by targeting NMB or its receptor to limit sneezing in those known to be infected, the researchers hold.

"A sneeze can create 20,000 virus-containing droplets that can stay in the air for up to 10 minutes," Liu said. "By contrast, a cough produces closer to 3,000 droplets, or about the same number produced by talking for a few minutes. To prevent future viral outbreaks and help treat pathological sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them. By identifying neurons that mediate the sneeze reflex, as well as neuropeptides that activate these neurons, we have discovered targets that could lead to treatments for pathological sneezing or strategies for limiting the spread of infections."

The findings were published Tuesday in the journal Cell.