Localization of TRP channels in healthy oral mucosa from human donors.

The oral cavity is exposed to a remarkable range of noxious and innocuous conditions, including temperature fluctuations, mechanical forces, inflammation and environmental and endogenous chemicals. How such changes in the oral environment are sensed is not completely understood. Transient receptor potential (TRP) ion channels are a diverse family of molecular receptors that are activated by chemicals, temperature changes, and tissue damage. In non-neuronal cells, TRP channels play roles in inflammation, tissue development, and maintenance. In somatosensory neurons TRP channels mediate nociception, thermosensation, and chemosensation. To assess whether TRP channels might be involved in environmental sensing in the human oral cavity, we investigated their distribution in human tongue and hard palate biopsies. TRPV3 and TRPV4 were expressed in epithelial cells with inverse expression patterns where they likely contribute to epithelial development and integrity. TRPA1 immunoreactivity was present in fibroblasts, immune cells, and neuronal afferents, consistent with known roles of TRPA1 in sensory transduction and response to damage and inflammation. TRPM8 immunoreactivity was found in lamina propria and neuronal subpopulations including within the end bulbs of Krause, consistent with a role in thermal sensation. TRPV1 immunoreactivity was identified in intraepithelial nerve fibers and end bulbs of Krause, consistent with roles in nociception and thermosensation. TRPM8 and TRPV1 immunoreactivity in end bulbs of Krause suggest that these structures contain a variety of neuronal afferents, including those that mediate nociception, thermosensation and mechanotransduction. Collectively, these studies support the role of TRP channels in oral environmental surveillance and response. Significance Statement Oral mucosa experiences a myriad of environmental fluctuations during feeding, speech, and daily life that they respond to for normal functions. These environmental stimuli are transduced by molecular receptors, including those of the Transient Receptor Potential (TRP) family of cation channels that reside in the membranes of mucosal cells and somatosensory neurons. The distribution of TRP channels that transduce chemical, biological, and thermal stimuli in oral mucosa are not well defined. This manuscript identifies the histological distribution of TRP channels in healthy oral tissues and develops hypotheses about how localization lends to their essential roles in oral functions and maintenance of homeostasis.