Morphological foundations of pain processing in dental pulp

Abstract

Dental pulp is densely innervated by sensory afferents that are primarily involved in nociception. Elucidating the type and properties of these afferents and their distribution patterns within the dental pulp is crucial for understanding the mechanisms of acute dental pain and dental hypersensitivity. Recent studies on the release of the transmitter glutamate and the expression of glutamate receptors and vesicular glutamate transporters (VGLUT) in the pulpal axons and trigeminal ganglion (TG) have suggested the possibility of a distinct glutamate signaling mechanism underlying the peripheral processing of dental pain. This review discusses recent findings on the innervation of dental pulp and glutamate signaling by pulpal axons. First, recent findings on the morphological features and types of axons innervating the dental pulp are summarized. Then, glutamate signaling in the dental pulp and changes in the expression of VGLUT1 and VGLUT2 in the pulpal axons and TG neurons following pulpal inflammation are explained. Finally, findings on glutamate release from odontoblasts are briefly described.

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

“…The fraction of myelinated Piezo1+ axons of all Piezo1+ axons decreased significantly between the radicular pulp (55.9 ± 6.0%) and the peripheral pulp (2.0% ± 1.0%), whereas the fraction of unmyelinated Piezo1+ axons increased significantly from 44.1% ± 6.0 % in the radicular pulp to 98.0% ± 1.0% in the peripheral pulp ( Figure 4D ), suggesting that virtually all Piezo1+ myelinated axons in the radicular pulp lose their myelin and become unmyelinated at the peripheral pulp. This assumption can also be supported by a previous study, showing shedding of myelin sheath in myelinated axons in the rat dental pulp ( Figure 4E , modified from Bae and Yoshida, 2020 ).…”

“… Electron micrographs showing immunostaining for Piezo1 (arrowheads) in myelinated (asterisks) and unmyelinated axons (arrows) in the radicular (A) , the core of the coronal (B) , and the peripheral (C) regions of the human dental pulp, and a histogram showing the fraction of Piezo1+ myelinated and unmyelinated axons of all Piezo1+ axons in each region of the human dental pulp (D) , and an electron micrograph of myelinated axon showing shedding of its myelin sheath during its course in the rat dental pulp [ (E) , modified from Bae and Yoshida, 2020 ]. Piezo1+ myelinated axons are more frequent in the radicular pulp than in the core of the coronal pulp, and virtually all Piezo1+ axons are unmyelinated in the peripheral pulp, suggesting that most Piezo1+ myelinated axons in the radicular pulp lose their myelin and become unmyelinated in the peripheral pulp.…”

Successful management of dentin hypersensitivity: A narrative review

“…21 Further studies have demonstrated that this increased fluid movement into the dentinal tubules excites both C-and Aδ-fibers in the dentin-pulp junction, which in turn activates the dental pain signaling pathway. 22,23 The expression of thermosensitive and mechanosensitive receptors, as well as voltage-gated ion channels involved in pain signaling in the primary dental afferent neurons, 19 further supports the hydrodynamic theory.…”

Intercellular crosstalk in adult dental pulp is mediated by heparin-binding growth factors Pleiotrophin and Midkine

“…This neural component of DP tissues remains relevant after development. In adult tissue, peripheral axons comprise 40% of DP volume (40), are the basis for pain processing (41), and participate in immune response (42,43). Although neurons cannot be isolated by the tissue digestion techniques applied in the present work, we were able to show that glial cells alone, myelinated and non-myelinated Schwann cells, comprise 12.39% of the DP cell population.…”