Sneezing and coughing protect our airways by helping expel pathogens, but viruses can exploit these reflexes to spread. Scientists at Washington University School of Medicine found that although similar irritants trigger both reflexes, they are governed by different sensory neurons.
Sneezing is activated through sensory fibers that innervate the nasal mucosa, while coughing is controlled by other fibers located in the lower respiratory tract. Experiments on mice revealed that sneezing is controlled by neurons with the MrgprC11 receptor, while coughing is managed by neurons with the somatostatin receptor (SST).
The distinction between sneezing and coughing could help develop new treatments for these symptoms during respiratory infections and allergies. These treatments would target neural pathways and could provide relief even for chronic sneezing and coughing.
4 Groups of Sensory Neurons Innervate the Nasal
Scientists studied the sensory fibers innervating the nasal mucosa and identified four groups of neurons:
- MrgprD Neurons: These neurons are responsible for sensing mechanical pain and histamine-independent itching. They innervate the front of the nose but not the back. Since sneezing can be triggered by sensory fibers in both the front and back of the nose, these neurons are likely not involved in sneezing.
- SST Neurons: This group of neurons responds to serotonin and interleukin-31 (IL-31), causing itching. They also have receptors for capsaicin, the substance found in hot peppers. SST neurons’ innervation in the nasal cavity is relatively sparse.
- TRPM8 Neurons: These neurons are sensitive to cold and menthol found in peppermint. Although cold can cause rhinorrhea (excess mucus production), it rarely triggers sneezing.
- MrgprC11 Neurons: This group of neurons is responsible for sneezing. These neurons densely innervate the nasal walls, septum, and especially the nasal turbinates, which are highly sensitive to environmental irritants. Interestingly, these same neurons are found in the lower airways but do not affect coughing.
Sensory neurons MrgprC11 are different from those that innervate the skin, which explains why the same irritants can trigger different reflexes, such as skin itching and sneezing.
MrgprC11 – Sneezing Neurons and a New Target for Treating Allergies and Sneezing in Respiratory Infections
When scientists genetically turned off MrgprC11 neurons in mice, the mice almost completely stopped sneezing, even when exposed to capsaicin, histamine, and serotonin, which usually cause sneezing.
MrgprC11 neurons are associated with both allergic and infectious sneezing. Disabling MrgprC11 neurons significantly reduced allergic sneezing and nearly eliminated sneezing during the flu. Suppressing MrgprC11 neurons could serve as the basis for developing new treatments for allergic rhinitis and sneezing during flu infections.
One method of suppressing MrgprC11 involves using the sodium channel blocker QX-314 in combination with the BAM peptide (bovine adrenal medulla substance 8-22, an agonist of MrgprC11). This method effectively reduced sneezing caused by allergies and the flu in mice.
SST – Cough Neurons
Different groups of sensory neurons trigger coughing and sneezing. MrgprC11 neurons, which are actively involved in sneezing, do not influence coughing. However, SST neurons, which densely innervate the trachea, play a key role in initiating cough.
SST sensory neurons express serotonin and IL-31 receptors and are responsible for itch sensations caused by serotonin and IL-31 receptor agonists in the skin. Activation of SST neurons triggered strong coughing reactions in mice.
Interestingly, disabling SST neurons significantly increased spontaneous coughing in mice, suggesting that SST neurons may suppress the transmission of cough signals.
Conclusion
Sneezing and coughing are protective reflexes that help the body expel irritants and viruses, but different neurons activate them. Sensory neurons MrgprC11 innervate the nasal cavity, respond to irritants, and are responsible for sneezing. SST neurons innervate the lower airways, are sensitive to inflammatory mediators, and are responsible for coughing.
Suppressing MrgprC11 neurons could be an effective strategy for treating allergies and symptoms of respiratory viral infections without the side effects of traditional antihistamines and corticosteroids.
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Reference
Divergent sensory pathways of sneezing and coughing
