Defining the Targets and Function of Direct Trigeminal Sensory Innervation to Salivary Glands

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PROJECT SUMMARY: Saliva is essential for oral and global health. The indispensable oral fluid - produced by salivary glands - facilitates chewing, swallowing, speaking, and gustation. Loss of saliva (i.e. dry mouth) represents a significant health burden, and can be caused by cancer treatments, medications (e.g. anti-hypertensives), or autoimmune destruction of the gland. Patients report significant suffering when they lose saliva because they begin to experience life-long morbidities, such as alterations in taste, loss of appetite, mucosal irritation and oral pain. To date, additional treatments and therapies are needed to stimulate saliva production to alleviate dry mouth. The autonomic nervous system is the primary controller of saliva production and release. However, the brain and other neuronal components provide input to stimulate or inhibit these salivary autonomic neurons. Here, we investigate a novel aspect of the nervous system that may influence salivary gland function: the trigeminal somatosensory neurons that innervate the glands. We hypothesize that somatosensory neurons innervating the gland respond to local stressors and influence saliva production. The overall objective of this application is to use both small and large animal models to a) examine the glandular cell targets of the trigeminal sensory innervation, b) define the molecular identity of gland-innervating sensory neurons, c) characterize the stimuli that activate sensory neurons, and d) determine how sensory innervation influences saliva production. We will use an array of powerful, cutting-edge approaches to develop a comprehensive view of these enigmatic neurons across mammalian species. Our studies will reveal new information on the topographical and molecular mapping of sensory innervation in the gland, and the functional involvement of sensory neurons in saliva production. Ultimately, new therapeutic strategies will develop from this work that target increasing saliva production in patients suffering from dry mouth.