Piezo1-pannexin-1-P2X 3 axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity.

Autor: Ohyama S; Department of Physiology, Tokyo Dental College, Tokyo, Japan.; Oral Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan., Ouchi T; Department of Physiology, Tokyo Dental College, Tokyo, Japan., Kimura M; Department of Physiology, Tokyo Dental College, Tokyo, Japan., Kurashima R; Department of Physiology, Tokyo Dental College, Tokyo, Japan., Yasumatsu K; Tokyo Dental Junior College, Tokyo, Japan., Nishida D; Oral Health Science Center, Tokyo Dental College, Tokyo, Japan., Hitomi S; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.; Division of Physiology, Kyushu Dental University, Fukuoka, Japan., Ubaidus S; Department of Physiology, Tokyo Dental College, Tokyo, Japan., Kuroda H; Department of Physiology, Tokyo Dental College, Tokyo, Japan.; Department of Dental Anesthesiology, Kanagawa Dental University, Yokosuka, Japan., Ito S; Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo, Japan., Takano M; Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo, Japan., Ono K; Division of Physiology, Kyushu Dental University, Fukuoka, Japan., Mizoguchi T; Oral Health Science Center, Tokyo Dental College, Tokyo, Japan., Katakura A; Department of Oral Pathological Science and Surgery, Tokyo Dental College, Tokyo, Japan., Shibukawa Y; Department of Physiology, Tokyo Dental College, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Frontiers in physiology [Front Physiol] 2022 Dec 14; Vol. 13, pp. 891759. Date of Electronic Publication: 2022 Dec 14 (Print Publication: 2022).
DOI: 10.3389/fphys.2022.891759
Abstrakt: According to the "hydrodynamic theory," dentinal pain or sensitivity is caused by dentinal fluid movement following the application of various stimuli to the dentin surface. Recent convergent evidence in Vitro has shown that plasma membrane deformation, mimicking dentinal fluid movement, activates mechanosensitive transient receptor potential (TRP)/Piezo channels in odontoblasts, with the Ca 2+ signal eliciting the release of ATP from pannexin-1 (PANX-1). The released ATP activates the P2X 3 receptor, which generates and propagates action potentials in the intradental Aδ afferent neurons. Thus, odontoblasts act as sensory receptor cells, and odontoblast-neuron signal communication established by the TRP/Piezo channel-PANX-1-P2X 3 receptor complex may describe the mechanism of the sensory transduction sequence for dentinal sensitivity. To determine whether odontoblast-neuron communication and odontoblasts acting as sensory receptors are essential for generating dentinal pain, we evaluated nociceptive scores by analyzing behaviors evoked by dentinal sensitivity in conscious Wistar rats and Cre-mediated transgenic mouse models. In the dentin-exposed group, treatment with a bonding agent on the dentin surface, as well as systemic administration of A-317491 (P2X 3 receptor antagonist), mefloquine and 10 PANX (non-selective and selective PANX-1 antagonists), GsMTx-4 (selective Piezo1 channel antagonist), and HC-030031 (selective TRPA1 channel antagonist), but not HC-070 (selective TRPC5 channel antagonist), significantly reduced nociceptive scores following cold water (0.1 ml) stimulation of the exposed dentin surface of the incisors compared to the scores of rats without local or systemic treatment. When we applied cold water stimulation to the exposed dentin surface of the lower first molar, nociceptive scores in the rats with systemic administration of A-317491, 10 PANX, and GsMTx-4 were significantly reduced compared to those in the rats without systemic treatment. Dentin-exposed mice, with somatic odontoblast-specific depletion, also showed significant reduction in the nociceptive scores compared to those of Cre-mediated transgenic mice, which did not show any type of cell deletion, including odontoblasts. In the odontoblast-eliminated mice, P2X 3 receptor-positive A-neurons were morphologically intact. These results indicate that neurotransmission between odontoblasts and neurons mediated by the Piezo1/TRPA1-pannexin-1-P2X 3 receptor axis is necessary for the development of dentinal pain. In addition, odontoblasts are necessary for sensory transduction to generate dentinal sensitivity as mechanosensory receptor cells.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Ohyama, Ouchi, Kimura, Kurashima, Yasumatsu, Nishida, Hitomi, Ubaidus, Kuroda, Ito, Takano, Ono, Mizoguchi, Katakura and Shibukawa.)
Databáze: MEDLINE
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