Expression of Piezo1 in the Trigeminal Neurons and in the Axons That Innervate the Dental Pulp

Abstract

Information on the neurons and axons that express the mechanosensitive channel Piezo1 and its expression in axons innervating the dental pulp may help understand the nature of the Piezo1-mediated mechanosensation and the underlying mechanism of dentin sensitivity elicited by mechanical stimuli. For this, we here investigated the neurochemical properties of the neurons in the rat trigeminal ganglion (TG) and their axons in its sensory root that express Piezo1 and the expression of Piezo1 in the rat and human dental pulp by light and electron microscopic immunohistochemistry and quantitative analysis. Piezo1 was expressed mainly in medium-sized and large TG neurons. Piezo1-immunopositive (+) neurons frequently coexpressed the marker for neurons with myelinated axons, NF200, but rarely the markers for neurons with unmyelinated axons, CGRP or IB4. In the sensory root of TG, Piezo1 was expressed primarily in small myelinated axons (Aδ, 60.2%) but also in large myelinated (Aβ, 24.3%) and unmyelinated (C, 15.5%) axons. In the human dental pulp, Piezo1 was expressed in numerous NF200+ axons, which formed a network in the peripheral pulp and often “ascended” toward the dentin. Most Piezo1+ myelinated axons in the radicular pulp became unmyelinated in the peripheral pulp, where Piezo1 immunoreaction product was associated with the axonal plasma membrane, suggesting a functional role of Piezo1 in the peripheral pulp. These findings suggest that Piezo1 is involved primarily in mediating the acute pain elicited by high-threshold mechanical stimuli, and that the Piezo1-mediated dental mechanotransduction occurs primarily in the axons in the peripheral pulp.

Immunolocalization of the mechanogated ion channels PIEZO1 and PIEZO2 in human and mouse dental pulp and periodontal ligament

“…To the best of our knowledge, this is the first study to analyze the presence of PIEZO1 and PIEZO2 in human teeth. However, our data did not suggest the presence of PIEZO1 or PIEZO2 in the pulp nerve fibers, as previously reported (Cho et al, 2022;Han et al, 2022;Sato et al, 2018;Won et al, 2017). The results for the periodontal ligament were consistent with those previously observed in mice (see Lukacs et al, 2023).…”

Mechanobiology of Dental Pulp Cells

“…Piezo1 is also expressed in nerve fibers within dental pulp. In the case of fibers, its expression in A was shown in 60.2% of small myelinated axons (Aδ) and 24.3% of large myelinated axons (Aβ), while in the case of fibers C its expression was noticed in 15.5% of unmyelinated axons [ 93 ]. Neurons engaged in signal transmission from dental pulp also express the Piezo2 mechanosensitive receptor.…”

Dentin Mechanobiology: Bridging the Gap between Architecture and Function

“…Although numerous studies have shown that PIEZO1 and 2 channels share the same overall architecture and domain composition, there are differences in cellular force-transmission pathways, indicating that PIEZO1 and 2 channels do not have exactly the same functional mechanism [ 73 ]. In vivo studies have demonstrated that while PIEZO1 channels are involved in mediating dental pain in models induced by high-threshold stimuli, PIEZO2 channels act as a low-threshold mechano-receptor that evokes pain in response to weak stimuli [ 74 , 75 ]. Xu et al reported that PIEZO1 and 2 channels together regulate inflammatory and reparative responses in odontoblasts in response to fluid shear stress overloading upon dentin injury, with PIEZO1 channels being more predominant in mechano-transduction through the integrin β1/Erk1 and Wnt/β-catenin signaling pathways [ 58 ].…”