Whether it's hay fever in the summer or a winter cold, we all know the tickling sensation that pre-empts a sneeze.
Amid the pandemic, sneezing is among the coronavirus' main routes of transmission, however, the biological pathways behind the reflex were poorly understood.
To learn more, scientists from the Washington University School of Medicine in St. Louis exposed mice to capsaicin, a pungent compound in chilli peppers that makes rodents – and humans – sneeze.
The scientists examined nerve cells in the mice that are known to react to capsaicin, discovering a specific class of cells that trigger sneezing.
After blocking these "sneeze signals", the animal's reflex was "greatly reduced".
With a single sneeze releasing up to 20,000 virus-rich droplets, drugs that "turn off" the reflex could help to stem the spread of infections.
"Better understanding what causes us to sneeze, specifically how neurones [nerve cells] behave in response to allergens and viruses, may point to treatments capable of slowing the spread of infectious respiratory diseases via sneezes," said study author Dr Qin Liu.
"So many people, including members of my own family, sneeze because of problems such as seasonal allergies and viral infections.
"Our goal is to understand how neurones behave in response to allergies and viral infections, including how they contribute to itchy eyes, sneezing and other symptoms".
The central nervous system's "sneeze-evoking region" was identified more than 20 years ago. Nevertheless, the reflex's trigger – on a cellular level – remained unclear.
To learn more, the Washington scientists exposed a group of mice to capsaicin-containing droplets. They first identified the specific class of neurones that cause sneezing when exposed to the pungent compound.
The team then looked for molecules called neuropeptides, which transmit sneeze signals to those neurones, discovering so-called neuromedin B (NMB) was required for the reflex.
When NMB-sensitive cells were eliminated in the mice, sneezing was blocked, as reported in the journal Cell.
"Interestingly, none of these sneeze-evoking neurones were housed in any of the known regions of the brainstem linked to breathing and respiration," said Dr Liu.
"Although we found sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found the cells in those two regions were directly connected via their axons, the wiring of nerve cells."
Exposing the mice to NMB also stimulated sneezing.
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Although it is early days, the scientists hope NMB-targeted treatments could limit the spread of various infections.
"A sneeze can create 20,000 virus-containing droplets that can stay in the air for up to 10 minutes," said Dr Liu.
"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 sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them.
"By identifying neurones that mediate the sneeze reflex, as well as neuropeptides that activate these neurones, we have discovered targets that could lead to treatments for sneezing or strategies for limiting the spread of infections".
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