The oral somatosensory system relays essential information about mechanical stimuli to enable oral functions such as feeding and speech. The neurochemical and anatomical diversity of sensory neurons across oral cavity sites have not been systematically compared. To address this gap, we analyzed healthy human tongue and hard-palate innervation. Biopsies were collected from 12 volunteers and underwent fluorescent immunohistochemistry (≥2 specimens per marker/

No abstract

The oral somatosensory system relays essential information about mechanical stimuli to enable oral functions such as feeding and speech. The neurochemical and anatomical diversity of sensory neurons across oral cavity sites have not been systematically compared. To address this gap, we analyzed healthy human tongue and hard palate innervation. Biopsies were collected from 12 volunteers and underwent multiplex fluorescent immunohistochemistry (≥2 specimens per marker/structure). Afferents were analyzed for markers of neurons (βIII tubulin), myelinated afferents (neurofilament heavy, NFH), and Merkel cells and taste cells (keratin 20, K20). Hard-palate innervation included Meissner's corpuscles, glomerular endings, Merkel cell-neurite complexes, and free nerve endings. The organization of these somatosensory endings is reminiscent of fingertips, suggesting that the hard palate is equipped with a rich repertoire of sensory neurons for pressure sensing and spatial localization of mechanical inputs, which are essential for speech production and feeding. Likewise, the tongue is innervated by afferents that impart it with exquisite acuity and detection of moving stimuli that support flavor construction and speech. Filiform papillae contain end bulbs of Krause, as well as endings that have not been previously reported, including subepithelial neuronal densities, and NFH+ neurons innervating basal epithelium. Fungiform papillae had Meissner's corpuscles and densities of NFH+ intraepithelial neurons surrounding taste buds. The differing compositions of sensory endings within filiform and fungiform papillae suggest that these structures have distinct roles in mechanosensation. Collectively, this study has identified previously undescribed afferent endings in human oral tissues and provides an anatomical framework for understanding oral mechanosensory functions.

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.