Abstract：
The dental pulp is a highly innervated tissue transmitting pain-related sensations in the tooth. Consequently, understanding the intricacies of its innervation mechanism in odontogenesis is crucial for gaining insights into dental pain and developing dental pain-modulating agents. This study examined neuroregulatory molecules such as neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin-4 [NTF-4], and neurturin [NRTN]) and neuroinhibitory factors (slit2, ephrin isoforms and netrin-1) in developing rat teeth with follicles. NGF, BDNF and NRTN transcriptions showed time-dependent upregulation, particularly during the root formation stage. In contrast, NTF-4 mRNA was highly expressed at the cap stage, but became downregulated over time. Slit2 and ephrin-B2 expression was distinct at the cap stage and then downregulated in a time-dependent manner. Ephrin-A5 and netrin-1 expression did not significantly change. Immunofluorescence analysis revealed a robust expression of both ephrin-B2 and slit2 in the outer and inner dental epithelia of the enamel organ, a non-neurogenic tissue, during the cap stage of 3rd molar germs. In contrast, BDNF was predominantly localized in dental papilla cells and odontoblasts during the root formation stage. These results suggest that neuroregulatory molecules, such as BDNF, slit2 and ephrin-B2, may be important in identifying therapeutic targets for modulating dental pulp pain.
摘要：
牙髓是在牙齿中传递疼痛相关感觉的高度神经支配的组织。因此,了解其在牙本质形成中的神经支配机制的复杂性对于深入了解牙齿疼痛和开发牙齿疼痛调节剂至关重要。这项研究检查了神经调节分子，例如神经营养因子（神经生长因子[NGF]，脑源性神经营养因子[BDNF]，神经营养蛋白-4[NTF-4]，和neurturin[NRTN]）和神经抑制因子（slit2，ephrin同工型和netrin-1）在发育中有卵泡的大鼠牙齿中。NGF,BDNF和NRTN转录显示时间依赖性上调，特别是在根形成阶段。相比之下,NTF-4mRNA在cap阶段高表达，但随着时间的推移变得下调。Slit2和ephrin-B2的表达在cap阶段是不同的，然后以时间依赖性方式下调。Ephrin-A5和netrin-1表达没有显著改变。免疫荧光分析显示，在釉质器官的外部和内部牙齿上皮中，ephrin-B2和slit2均有稳健表达，非神经源性组织，在第3磨牙细菌的盖帽阶段。相比之下,在牙根形成阶段，BDNF主要位于牙乳头细胞和成牙本质细胞中。这些结果表明，神经调节分子，比如BDNF,slit2和ephrin-B2在确定调节牙髓疼痛的治疗靶标中可能很重要。
