Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp.
Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp.
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DOI：
10.1016/j.joen.2015.12.010
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发表时间：
2016-04
影响因子：
4.2
通讯作者：
Gibbs JL
中科院分区：
文献类型：
--
作者：
Burns LE;Ramsey AA;Emrick JJ;Janal MN;Gibbs JL
牙髓独特的神经支配和解剖学特征导致了一个显著的发现，即对牙髓组织的任何物理刺激都是痛苦的。此外，当病理过程，如龋齿，影响牙齿，并产生炎症的牙髓，所经历的疼痛可能是相当激烈和衰弱。为了更好地了解这些潜在的神经生物学机制，并确定新的镇痛靶点牙髓源性疼痛，我们已经开发了一个强大的离体模型，使用人类牙齿切片。收集无龋、刚拔除的牙齿，并纵向切成1 mm厚的切片，其中含有牙髓和周围的矿化组织。将36名患者的牙齿切片暴露于60 μ M辣椒素中，以刺激牙髓中神经末梢释放降钙素基因相关肽（CGRP）。使用混合模型ANOVA分析患者因素对辣椒素刺激的CGRP释放的影响。在辣椒素诱发的CGRP释放中观察到的变异性中约有1/3可归因于个体之间的差异。就个体因素而言，麻醉类型、性别或年龄对辣椒素刺激的CGRP释放没有影响。使用受试者内研究设计，观察到辣椒素对CGRP释放的显著影响。辣椒素刺激的CGRP从牙髓释放是高度可变的个体之间。受试者内研究设计提高了变异性，并最大限度地发挥了这种强大的翻译模型的潜力，以测试新型药物对人类外周伤害感受器的疗效。
The unique innervation and anatomical features of the dental pulp contribute to the remarkable finding that any physical stimulation of pulpal tissue is painful. Further, when pathological processes, such as caries, affect teeth, and produce inflammation of the pulp, the pain experienced can be quite intense and debilitating. To better understand these underlying neurobiological mechanisms, and identify novel analgesic targets for pulpally derived pain, we have developed a powerful ex vivo model using human tooth slices. Non-carious, freshly-extracted teeth were collected and sectioned longitudinally into 1mm thick slices containing both dental pulp and the surrounding mineralized tissues. Tooth slices from 36 patients were exposed to 60 uM capsaicin to stimulate the release of calcitonin gene-related peptide (CGRP) from nerve terminals in the pulp. Patient factors were analyzed for their affects on capsaicin-stimulated CGRP release using a mixed model ANOVA. Approximately 1/3 of the variability observed in capsaicin-evoked CGRP release was attributable to differences between individuals. In terms of individual factors, there was no effect of anesthesia type, sex or age on capsaicin-stimulated CGRP release. Using a within-subject study design, a significant effect of capsaicin on CGRP release was observed. Capsaicin-stimulated CGRP release from dental pulp is highly variable between individuals. A within-subject study design improves the variability and maximizes the potential of this powerful translational model to test the efficacy of novel pharmacotherapeutic agents on human peripheral nociceptors.