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

Cannizzaro, D. N.; Amorim, J.; Wilson, R. E.; Moehn, K. M.; Saravanan, A.; Vesela, I.; Gandhi, A. R.; Lombaert, I. M. A.; Emrick, J. J.

doi:10.64898/2026.08.06.743081

bioRxiv · 10.64898/2026.08.06.743081

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

Cannizzaro, D. N.·Amorim, J.·Wilson, R. E.·Moehn, K. M.·Saravanan, A.·Vesela, I.·Gandhi, A. R.·Lombaert, I. M. A.·Emrick, J. J.

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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 Whartons 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 Whartons ducts 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.

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Cannizzaro, D. N., Amorim, J., Wilson, R. E., Moehn, K. M., Saravanan, A., Vesela, I., Gandhi, A. R., Lombaert, I. M. A., Emrick, J. J.. 2026-08-12. Trpv1+ sensory innervation of the salivary gland drives pain and supports saliva secretion. https://doi.org/10.64898/2026.08.06.743081

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