C1-O-05Central Connectivity and Distribution of Transient Receptor Potential Melastatin 8 (TRPM8)-expressing Axons in the Brain stem and Dental pulp

Elucidation of synaptic connectivities of the specific primary sensory afferents, involved neurotransmitters and receptors may help understand how the specific sensation conveyed via particular sensory afferents is processed at the 1st relay nucleus. Transient receptor potential melastatin 8 (TRPM8) mediates detection of noxious cold and innocuous cool, and is expressed in the primary sensory neurons. In this presentation, we will talk about our recent findings on expression and central connectivities of TRPM8-positive (+) axons in the trigeminal sensory nuclei (TSN) and their coexpression with vesicular glutamate transporters (VGLUTs) in the dental pulp. TRPM8 was expressed in unmyelinated C fibers (76%) and small myelinated Αδ fibers (24%). TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, suggesting TRPM8-mediated cold from face and intraoral area is processed in different level of TSN. TRPM8+ boutons, compared to boutons from the same class of fiber types, showed unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. In the dental pulp, TRPM8+ axons were densely distributed in the peripheral pulp, coexpressed VGLUT2, but not VGLUT1, and which was upregulated following pulpal inflammation. These findings suggest that TRPM8 -mediated cold is processed in a unique manner and differently in the TSN and also suggest existence of VLGUT2-mediated glutamate signaling in TRPM8+ axons that may be underlying mechanism for acute cold pain and cold hypersensitivity following inflammation.