Electrophysiological Properties and Mechanical Sensitivity of Trigeminal Ganglionic Neurons That Innervate the Maxillary Sinus in Mice

TL;DR

This study identifies a specific type of nerve cell in mice that senses pain and pressure in the maxillary sinus, which could help improve understanding and treatment of sinus-related facial pain.

Contribution

The study identifies a distinct subgroup of trigeminal ganglionic neurons innervating the maxillary sinus with unique electrophysiological and molecular properties.

Findings

Maxillary sinus TG neurons are predominantly small-diameter C-afferent nociceptors with high thresholds and broad action potentials.

These neurons express Nav1.9 but show minimal Nav1.8 expression and limited overlap with Nav1.8-positive nociceptor populations.

A subset of these neurons expresses the mechanoreceptor Piezo2 and exhibits mechanically activated currents with varied adaptation profiles.

Abstract

The maxillary sinus is frequently implicated in facial pain syndromes arising from infection, neoplasia, dental procedures, and, importantly, migraine, which can mimic “sinus headache” and contribute to misdiagnosis and inappropriate antibiotic use. Despite the clinical burden of chronic maxillary sinus pain, the sensory neuron subtypes that convey nociceptive and mechanosensory signals from the sinus mucosa remain incompletely defined. In this study, trigeminal ganglion (TG) neurons innervating the maxillary sinus (maxillary sinus TG neurons) were retrogradely labeled with the fluorescent dye DiD in mice and characterized using ex vivo patch-clamp electrophysiology and single-cell RT-PCR. Maxillary sinus TG neurons were found to be predominantly small-diameter, C-afferent nociceptors with electrophysiologic features including high thresholds, repetitive firing, and broad action potentials. Notably, maxillary sinus TG neurons formed a distinct molecular and functional subgroup: they expressed Nav1.9, while showing minimal Nav1.8 expression and limited overlap with Nav1.8-positive nociceptor populations. A majority of maxillary sinus TG neurons were mechanically responsive, generating mechanically activated currents with heterogeneous adaptation profiles, and a subset expressed the mechanoreceptor Piezo2. Collectively, these findings identify maxillary sinus TG neurons as a specialized population of Nav1.9-enriched C-afferent nociceptors with mechanosensitive properties, providing a mechanistic framework for pressure-evoked sinus pain. This work advances the neurobiological basis of sinus-related pain and suggests that Nav1.9 and mechanoreceptor pathways may be potential therapeutic targets for conditions in which sinus symptoms overlap with migraine and other craniofacial pain disorders.

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