National Research Laboratory for Pain, Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea.
J Dent Res. 2011 Jun;90(6):771-6. doi: 10.1177/0022034511399906. Epub 2011 Mar 1.
Selective blockade of nociceptive neurons can be achieved by the delivery of permanently charged sodium channel blockers through the pores of nociceptive ion channels. To assess the feasibility of this application in the dental area, we investigated the electrophysiological and neurochemical characteristics of nociceptive dental primary afferent (DPA) neurons. DPA neurons were identified within trigeminal ganglia labeling with a retrograde fluorescent dye applied to the upper molars of adult rats. Electrophysiological studies revealed that the majority of dental primary afferent neurons showed characteristics of nociceptive neurons, such as sensitivity to capsaicin and the presence of a hump in action potential. Immunohistochemical analysis revealed a large proportion of DPA neurons to be IB(4)-positive and to express TRPV1 and P2X(3). Single-cell RT-PCR revealed mRNA expression of various nociceptive channels, including the temperature-sensitive TRPV1, TRPA1, TRPM8 channels, the extracellular ATP receptor channels P2X(2) and P2X(3), as well as the nociceptor-specific sodium channel, Na(V)1.8. In conclusion, DPA neurons have the electrophysiological characteristics of nociceptors and express several nociceptor-specific ion channels. Analysis of these data may assist in the search for a new route of entry for the delivery of membrane-impermeant local anesthetics.
通过将永久带电的钠离子通道阻断剂递送至伤害感受离子通道的孔中,可以实现伤害感受神经元的选择性阻断。为了评估该应用在牙科领域的可行性,我们研究了伤害感受性牙源性初级传入(DPA)神经元的电生理和神经化学特性。通过将逆行荧光染料应用于成年大鼠的上颌磨牙,在三叉神经节中鉴定出 DPA 神经元。电生理研究表明,大多数牙源性初级传入神经元表现出伤害感受神经元的特征,例如对辣椒素敏感和动作电位中存在峰。免疫组织化学分析显示,很大一部分 DPA 神经元为 IB(4)-阳性,并表达 TRPV1 和 P2X(3)。单细胞 RT-PCR 显示,多种伤害感受通道的 mRNA 表达,包括温度敏感的 TRPV1、TRPA1、TRPM8 通道、细胞外 ATP 受体通道 P2X(2)和 P2X(3),以及伤害感受器特异性钠离子通道 Na(V)1.8。总之,DPA 神经元具有伤害感受器的电生理特征,并表达几种伤害感受器特异性离子通道。对这些数据的分析可能有助于寻找新的途径来输送不可渗透细胞膜的局部麻醉剂。