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

bioRxiv [Preprint]. 2026 Aug 12:2026.08.06.743081. doi: 10.64898/2026.08.06.743081.

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.

PMID:42845312 | PMC:PMC13640602 | DOI:10.64898/2026.08.06.743081