Inhibiting Nav1.7 channels in pulpitis: An in vivo study on neuronal hyperexcitability.
Autor: | Lee KH; Department of Dental Hygiene, Division of Health Science, Dongseo University, Busan, 47011, Republic of Korea., Kim UJ; Department of Physiology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Cha M; Department of Physiology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. Electronic address: mhcha@yuhs.ac., Lee BH; Department of Physiology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. Electronic address: bhlee@yuhs.ac. |
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Jazyk: | angličtina |
Zdroj: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Jul 12; Vol. 717, pp. 150044. Date of Electronic Publication: 2024 May 03. |
DOI: | 10.1016/j.bbrc.2024.150044 |
Abstrakt: | Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its clinical importance, the correlation between neuronal activity and the expression of voltage-gated sodium channel 1.7 (Nav1.7) in the trigeminal ganglion (TG) during pulpitis is less investigated. The aim of this study was to examine the relationship between experimentally induced pulpitis and Nav1.7 expression in the TG and to investigate the potential of selective Nav1.7 modulation to attenuate TG abnormal activity associated with pulpitis. Acute pulpitis was induced at the maxillary molar (M1) using allyl isothiocyanate (AITC). The mice were divided into three groups: control, pulpitis model, and pulpitis model treated with ProTx-II, a selective Nav1.7 channel inhibitor. After three days following the surgery, we conducted a recording and comparative analysis of the neural activity of the TG utilizing in vivo optical imaging. Then immunohistochemistry and Western blot were performed to assess changes in the expression levels of extracellular signal-regulated kinase (ERK), c-Fos, collapsin response mediator protein-2 (CRMP2), and Nav1.7 channels. The optical imaging result showed significant neurological excitation in pulpitis TGs. Nav1.7 expressions exhibited upregulation, accompanied by signaling molecular changes suggestive of inflammation and neuroplasticity. In addition, inhibition of Nav1.7 led to reduced neural activity and subsequent decreases in ERK, c-Fos, and CRMP2 levels. These findings suggest the potential for targeting overexpressed Nav1.7 channels to alleviate pain associated with pulpitis, providing practical pain management strategies. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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