Abstract：
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.
摘要：
由于牙髓炎对周围神经组织的影响和慢性疼痛的持续存在，因此在临床管理中构成了重大挑战。尽管其临床重要性，在牙髓炎期间，神经元活动与三叉神经节（TG）中电压门控钠通道1.7（Nav1.7）表达之间的相关性研究较少。这项研究的目的是检查实验诱导的牙髓炎与TG中Nav1.7表达之间的关系，并研究选择性Nav1.7调节减弱与牙髓炎相关的TG异常活性的潜力。使用异硫氰酸烯丙酯（AITC）在上颌磨牙（M1）诱发急性牙髓炎。将小鼠分为三组：对照组，牙髓炎模型,和用ProTx-II治疗的牙髓炎模型，一种选择性Nav1.7通道抑制剂。手术后三天,我们使用体内光学成像对TG的神经活性进行了记录和比较分析。然后进行免疫组织化学和Westernblot以评估细胞外信号调节激酶（ERK）表达水平的变化。c-Fos,折叠素反应介质蛋白2（CRMP2），和Nav1.7频道。光学成像结果显示在牙髓炎TGs中明显的神经兴奋。Nav1.7表达表现出上调，伴随信号分子变化提示炎症和神经可塑性。此外,抑制Nav1.7导致神经活动减少，随后ERK减少，c-Fos,CRMP2级别。这些发现表明靶向过度表达的Nav1.7通道以减轻牙髓炎相关疼痛的潜力。提供实用的疼痛管理策略。
