Austah Obadah N, Ruparel Nikita B, Henry Michael A, Fajardo Roberto J, Schmitz James E, Diogenes Anibal
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
J Endod. 2016 Oct;42(10):1496-502. doi: 10.1016/j.joen.2016.06.009. Epub 2016 Aug 11.
Nociceptive neurons play a critical role in the detection of stimuli evoking actual or potential tissue injury. In addition, they are involved in neurogenic inflammation by the peripheral release of neuropeptides such as calcitonin gene-related peptide (CGRP). The dental pulp and periradicular tissues are innervated by capsaicin-sensitive neurons known to release CGRP. However, the role of these capsaicin-sensitive neurons in the development of apical periodontitis is largely unknown. The aim of this study was to evaluate the contribution of peptidergic neurons to the development of apical periodontitis.
Neonatal Sprague-Dawley rats were injected with vehicle (control group) or a single subcutaneous capsaicin dose to cause the selective ablation of peptidergic neurons (neonatal capsaicin group). Ablation of capsaicin-sensitive neurons was verified with confocal microscopy, capsaicin-induced eye-wipe nocifensive behavior test, and by measurement of immunoreactive CGRP levels in the dental pulp. Five weeks after ablation, standardized pulp exposures were made in the mandibular left first molars. Mandibles were harvested at 7, 14, 21, and 28 days after pulp exposure and imaged with micro-computed tomography (μCT) to quantify apical lesion volume. Data were analyzed by using 2-way ANOVA analysis with Bonferroni post hoc test.
Rats in the control group displayed a robust capsaicin-induced nocifensive behavior, which was nearly abolished in the neonatal capsaicin group. In addition, the neonatal capsaicin group showed a significant depletion of susceptible neurons and CGRP in the dental pulp compared with control. Importantly, micro-computed tomography analysis showed larger periradicular lesions at 7 and 14 days after pulp exposure in the neonatal capsaicin group when compared with control.
Results identify a protective role for capsaicin-sensitive neurons in the initial phase of apical periodontitis. Thus, interventions or disorders that alter activity of capsaicin-sensitive fibers are likely to alter the development of apical periodontitis.
伤害性神经元在检测引发实际或潜在组织损伤的刺激中起关键作用。此外，它们通过外周释放降钙素基因相关肽（CGRP）等神经肽参与神经源性炎症。牙髓和根尖周组织由已知释放CGRP的辣椒素敏感神经元支配。然而，这些辣椒素敏感神经元在根尖周炎发展中的作用很大程度上尚不清楚。本研究的目的是评估肽能神经元在根尖周炎发展中的作用。
将新生Sprague-Dawley大鼠注射媒介物（对照组）或单次皮下注射辣椒素剂量以导致肽能神经元的选择性消融（新生辣椒素组）。通过共聚焦显微镜、辣椒素诱导的擦眼伤害性防御行为试验以及测量牙髓中免疫反应性CGRP水平来验证辣椒素敏感神经元的消融。消融后5周，在下颌左侧第一磨牙进行标准化的牙髓暴露。在牙髓暴露后7、14、21和28天采集下颌骨，并用微型计算机断层扫描（μCT）成像以量化根尖病变体积。数据采用双向方差分析和Bonferroni事后检验进行分析。
对照组大鼠表现出强烈的辣椒素诱导的伤害性防御行为，而在新生辣椒素组中几乎消失。此外，与对照组相比，新生辣椒素组牙髓中易感神经元和CGRP显著减少。重要的是，微型计算机断层扫描分析显示，与对照组相比，新生辣椒素组在牙髓暴露后7天和14天时根尖周病变更大。
结果表明辣椒素敏感神经元在根尖周炎的初始阶段具有保护作用。因此，改变辣椒素敏感纤维活性的干预措施或疾病可能会改变根尖周炎的发展。
