Work

Trpv1 + sensory innervation of the salivary gland drives pain and supports saliva secretion

Year: 2026

Type: preprint

Abstract: ABSTRACT Sensory neurons have been increasingly recognized as vital contributors to deep tissue function. However, how these specialized neurons contribute to salivary gland function remains largely undefined. Here, we uncover a role for trigeminal somatosensory afferents in salivary gland perception and function using in situ -based classification, in vivo calcium imaging, behavioral assays, and targeted ablation. Retrograde labeling from the submandibular gland complex revealed substantial direct innervation from trigeminal neurons. Further categorization confirmed that Trpv1 + sensory neurons provided dense innervation of the Wharton’s ducts. TRPV1 agonist ductal infusion directly activated gland complex-associated neurons in the trigeminal ganglia and evoked a robust pain phenotype. Targeted Trpv1 + ablation disrupted Wharton’s duct’s structure and dramatically reduced stimulated saliva volume. Our work provides the first evidence that Trpv1 + sensory neurons maintain salivary architecture and are necessary for stimulated saliva production, revealing a vital interoceptive role for direct trigeminal innervation in submandibular gland health.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.08.06.743081