Why Do We Sneeze? | The Everyday Biologist

Sneezing feels like the simplest reflex there is. Something tickles your nose, and a moment later you’re doubled over expelling air at a speed that would get you a ticket on most highways. But underneath that simplicity is a surprisingly specific piece of biology: a dedicated population of nerve cells, a dedicated chemical messenger, and a dedicated circuit in the brainstem that has nothing to do with the circuit that makes you cough. Sneezing isn’t a generic “get the irritant out” response. It’s its own reflex, built from its own parts.

The nerve cells that actually cause sneezing

For a long time, researchers assumed sneezing and coughing were triggered by the same kind of sensory nerve fibers responding to the same kind of stimuli, just in different parts of the airway. A 2005 study on guinea pigs started to complicate that picture. Researchers labeled the trigeminal nerve cells that innervate the nasal mucosa and then tested how those cells responded to histamine and capsaicin (the compound that makes chili peppers burn) [1]. Only 60% of the nasal-specific neurons responded to capsaicin at all, and histamine activated a smaller subset of those, fewer than 40% [1]. Crucially, every single nasal neuron that responded to histamine also responded to capsaicin, but the reverse wasn’t true [1]. That’s the first clue that sneezing isn’t triggered indiscriminately. Something more selective is going on.

A 2024 study in Cell took this much further and actually found the specific cell type responsible [2]. Using mice, the researchers screened several populations of nasal sensory neurons, including cells marked by MrgprD, SST, TRPM8, and MrgprC11, activating each population individually and watching whether the mice sneezed. Activating MrgprD+ neurons didn’t produce sneezing. Activating SST+ neurons didn’t either. Cold-sensing TRPM8+ neurons, the ones that respond to menthol and cold air, also failed to trigger it [2]. Only one population worked: neurons expressing MrgprC11 but not MrgprA3. Chemically activating these cells with an MrgprC11-specific compound reliably produced sneezing, and when the researchers genetically wiped out this specific population, sneezing responses to a whole range of irritants, including capsaicin, histamine, and serotonin, were almost completely abolished [2]. These cells even mediated the sneezing associated with allergic rhinitis and with influenza infection in the mouse models tested. It’s a fairly clean result: a single, identifiable population of “sneeze neurons” sits upstream of a wide variety of triggers that would otherwise seem unrelated.

The messenger that carries the signal

Finding the right nerve cells is only half the story. Something has to carry the signal from those nerve cells to the brain, and that something turned out to be a peptide called neuromedin B, or NMB. When the sneeze-triggering MrgprC11+ neurons are activated, they release NMB, which then binds to NMB receptors (NMBR) on postsynaptic neurons in a specific brainstem region [2, 4]. Knock out the gene for NMB in these neurons, or knock out the NMB receptor entirely, and the sneeze reflex collapses even when the trigger (capsaicin, histamine, allergen exposure) is still fully present [2, 4]. Mice lacking the NMB receptor also failed to show the usual burst of c-Fos activation (a marker of neuronal activity) in the brainstem’s sneeze center after stimulation that should have triggered a sneeze [4]. NMB isn’t a side character here. It’s the specific handoff that has to happen for the signal to make it from nose to brainstem at all.

Other candidate messengers were tested and ruled out. Substance P, CGRP, and glutamate signaling through Vglut2 are all expressed by these nasal neurons too, but knocking each of them out individually didn’t impair sneezing [4]. That’s a useful negative result. It narrows the transmission mechanism down instead of leaving it as a vague pool of possible neurotransmitters.

Why sneezing and coughing aren’t the same reflex

This is where things get genuinely interesting, because sneezing and coughing look similar on the outside (both are sudden expulsions of air meant to clear an irritant) but the 2024 Cell paper found they run on almost entirely separate machinery [2].

The same MrgprC11+ neurons that trigger sneezing in the nose also extend into the trachea. You’d expect that if they mediate sneezing in one place, they’d mediate coughing in the other. They don’t. Activating tracheal MrgprC11+ neurons failed to produce any coughing response at all [2]. Instead, a different population entirely, SST+ neurons, turned out to mediate coughing in the trachea, even though those same SST+ neurons have no role in triggering sneezes in the nose [2]. The researchers confirmed this multiple ways: pharmacological activation of SST+ neurons with agents like Ly344864 and IL-31 reliably produced coughing, chemogenetic activation of the same population did too, and genetically ablating MrgprC11+ neurons had no effect on influenza-associated coughing even though it nearly eliminated influenza-associated sneezing in the same animals [2].

This divergence extends up the chain into the brainstem itself. Sneeze signals from the trigeminal nerve project to a region called the ventromedial spinal trigeminal nucleus, or SpV [4]. Cough signals from the vagus nerve, which carries sensory information from the lower airway, project instead to the nucleus tractus solitarius, or NTS [4]. From an evolutionary standpoint, having two separate detection systems for the upper and lower airway makes sense: some respiratory viruses, like early SARS-CoV-2 variants and RSV, mainly provoke coughing rather than sneezing, so a dual surveillance system catches threats that might otherwise slip past a single unified reflex [2].

The mechanics of a sneeze itself

Once the signal reaches the brainstem and crosses the threshold needed to trigger a response, sneezing isn’t executed by some purpose-built sneezing machinery. It’s executed by hijacking the brainstem’s existing respiratory control center, the same network of neurons that manages ordinary breathing [4]. This structure is called the central pattern generator, or CPG, and it normally handles the rhythm of inhaling and exhaling without you ever thinking about it. A sneeze temporarily reconfigures that rhythm into something much more violent.

The sequence runs in three stages [4]. First comes a deep, forceful inhalation, driven by the diaphragm and the muscles between the ribs, pulling in a much larger volume of air than a normal breath would. Second comes the compression phase: the vocal folds snap shut, sealing the airway, while the soft palate rises to close off the nasopharyngeal passage. Air builds up behind that closure, and intrapulmonary pressure spikes. Third, the glottis flies open and the trapped air is expelled explosively through the nose and mouth at once, carrying whatever irritant triggered the whole cascade along with it [3, 4]. That airflow isn’t gentle. Measurements have put sneeze airflow speeds at close to 100 kilometers per hour [3], and a single sneeze can release tens of thousands of aerosolized droplets that stay suspended in the air for minutes and travel several meters [3].

The distinction between sneezing and coughing shows up again here at the motor level. Sneezing requires that initial deep inhalation; it’s an obligatory part of the sequence, needed to generate enough pressure for the expulsion phase. Coughing is more flexible and can happen with little to no preliminary inhalation if the lungs already hold enough air [4]. Both reflexes depend on the same basic trick, precise timing of glottal closure and opening, but they get there through different triggering pathways and slightly different motor patterns.

Triggers beyond irritants

Chemical irritants like capsaicin, histamine, and allergens are the obvious sneeze triggers, but the reflex responds to some genuinely unusual inputs too, and these tell you something about how tangled the underlying wiring actually is.

The best documented is the photic sneeze reflex, sometimes called ACHOO syndrome (an acronym for autosomal dominant compelling helio-ophthalmic outburst, which is about as strained an acronym as medicine has produced). Sudden exposure to bright light, especially direct sunlight, triggers sneezing in a meaningful chunk of the population. It’s inherited in an autosomal dominant pattern, and prevalence estimates across different cohort studies land somewhere between 17% and 35% [4]. The mechanism isn’t fully worked out, but the leading idea is that in people with this trait, visual signals processed in the visual cortex spill over into somatosensory circuits that overlap with the trigeminal pathway, effectively cross-wiring “bright light” into “nasal irritant” [3, 4]. Sudden shifts to hot or cold air can produce a milder version of the same kind of cross-triggering, irritating nasal receptors directly even without a chemical stimulus present [4].

Allergic rhinitis represents the other major real-world trigger, and it’s worth separating from a simple allergic reaction because the sneezing itself follows a specific time course. On exposure to an allergen like pet dander or dust mites, mast cells in the nasal mucosa degranulate within 5 to 15 minutes, releasing histamine along with other inflammatory mediators [4]. That histamine directly excites the trigeminal nerve endings responsible for sneezing, on top of promoting the runny nose and congestion that show up alongside it. A second, later wave follows roughly 4 to 6 hours after exposure, driven by cytokines like IL-4 and IL-13 that draw eosinophils and other immune cells into the nasal tissue and sustain the inflammation for much longer [4]. Over time, in chronic cases, this repeated immune activity can leave the nasal mucosa in a persistently hyperreactive state, to the point where ordinary triggers like cold air or tobacco smoke start setting off sneezing that wouldn’t have happened before the allergic process took hold [4].

When the reflex breaks

Because sneezing depends on such a specific pathway, from trigeminal sensory neurons through NMB signaling to a defined patch of brainstem tissue, damage anywhere along that chain can knock the reflex out entirely, and the clinical cases where this happens are oddly informative.

The clearest example is Wallenberg’s syndrome, also called lateral medullary syndrome, which usually results from a vertebral artery dissection or blockage that damages the lateral medulla [4]. Patients with this condition often lose the physical ability to sneeze completely, even though they continue to feel the buildup, the itchy, pressured sensation right before a sneeze would normally happen [4]. That dissociation is the interesting part. It shows that the sensory side of the pathway, the part that registers the urge, and the motor side, the part that actually executes the explosive exhalation, can be knocked apart from each other by a fairly localized injury. It also confirms that the human sneeze center isn’t confined to one tidy structure the way animal studies sometimes suggest, but instead depends on a broader network across the lateral medulla [4].

There’s also a psychological version of the same breakdown. Intractable psychogenic sneezing shows up mostly in adolescent females, presents with completely normal anatomical scans, and resists standard antihistamines and decongestants because the pathology isn’t in the nose at all [4]. It’s typically driven by underlying psychological stress and looks distinct from a real sneeze on close inspection: shorter inhalation, no mucosal secretions, eyes that often stay open through the expulsion [4]. Treatment leans on cognitive behavioral therapy and biofeedback rather than anything pharmacological, and the pharmacological treatments that do get used are aimed at lowering background anxiety rather than blocking the reflex directly [4].

Summary

Sneezing looks like a blunt, reflexive response to nasal irritation, but the biology underneath it is precise. A single, genetically identifiable population of nerve cells (MrgprC11-positive, MrgprA3-negative) sits at the entry point for a wide range of triggers, from capsaicin to histamine to influenza infection, and none of those triggers can produce a sneeze without this population intact. Once activated, these neurons release a specific peptide, NMB, that has to bind its receptor in the brainstem for the signal to go anywhere. From there, the reflex borrows the brainstem’s ordinary breathing circuitry and repurposes it into a three-stage sequence of inhalation, compression, and explosive release. And despite sharing a superficial resemblance to coughing, sneezing runs on an almost entirely separate set of nerve cells, peptides, and brainstem targets, which is why the two reflexes can be selectively knocked out or triggered independently of each other in experimental settings. What feels like the simplest reflex in the body turns out to be one of the more cleanly mapped ones, at least at the level of which cells, which peptide, and which circuit are actually responsible.

Common Questions

Is sneezing the same reflex as coughing?

No. They share some surface similarities, like the forceful expulsion of air, but they're triggered by different nerve populations and wired to different parts of the brainstem. Sneezing runs through the trigeminal nerve to a region called the SpV, while coughing runs through the vagus nerve to the nucleus tractus solitarius (NTS).

Why does pepper or dust make you sneeze but cold air usually doesn't?

Capsaicin, histamine, and similar irritants activate a specific nasal nerve population that triggers sneezing. Cold-sensing nerve fibers exist in the nose too, but activating them experimentally doesn't reliably produce sneezing, which lines up with the fact that most people don't sneeze from cold air alone.

What is the photic sneeze reflex?

It's a genetic trait, inherited in an autosomal dominant pattern, where sudden exposure to bright light triggers sneezing. Estimates put its prevalence somewhere between 17% and 35% of the population, so it's fairly common. The exact mechanism isn't fully worked out, but it likely involves visual signals crossing over into somatosensory pathways in the brain.

Can something in the brain actually stop you from being able to sneeze?

Yes. In Wallenberg's syndrome, a type of stroke affecting the lateral medulla, patients can lose the physical ability to sneeze entirely, even though they still feel the urge building up. It's a striking demonstration that the motor side of the reflex and the sensory side are handled by separate machinery.

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