Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan.
Mol Pain. 2013 Sep 30;9:49. doi: 10.1186/1744-8069-9-49.
The trigeminal subnuclei interpolaris/caudalis transition zones (Vi/Vc) play an important role in orofacial deep pain, however, the role of primary afferent projections to the Vi/Vc remains to be determined. This study investigated the functional significance of hyperalgesia to the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (trkB) signaling system in trigeminal ganglion (TRG) neurons projecting to the Vi/Vc transition zone following masseter muscle (MM) inflammation.
The escape threshold from mechanical stimulation applied to skin above the inflamed MM was significantly lower than in naïve rats. Fluorogold (FG) labeling was used to identify the TRG neurons innervating the MM, while microbeads (MB) were used to label neurons projecting to the Vi/Vc region. FG/MB-labeled TRG neurons were immunoreactive (IR) for BDNF and trkB. The mean number of BDNF/trkB-IR small/medium-diameter TRG neurons was significantly higher in inflamed rats than in naïve rats. In whole-cell current-clamp experiments, the majority of dissociated small-diameter TRG neurons showed a depolarization response to BDNF that was associated with spike discharge, and the concentration of BDNF that evoked a depolarizing response was significantly lower in the inflamed rats. In addition, the relative number of BDNF-induced spikes during current injection was significantly higher in inflamed rats. The BDNF-induced changes in TRG neuron excitability was abolished by tyrosine kinase inhibitor, K252a.
The present study provided evidence that BDNF enhances the excitability of the small-diameter TRG neurons projecting onto the Vi/Vc following MM inflammation. These findings suggest that ganglionic BDNF-trkB signaling is a therapeutic target for the treatment of trigeminal inflammatory hyperalgesia.
三叉神经亚核间/尾核过渡区（Vi/Vc）在口面部深部疼痛中起重要作用，然而，向 Vi/Vc 投射的初级传入投射的作用仍有待确定。本研究探讨了三叉神经节（TRG）神经元中脑源性神经营养因子（BDNF）-酪氨酸激酶 B（trkB）信号系统对磨牙肌（MM）炎症后向 Vi/Vc 过渡区投射的超敏反应的功能意义。
施加于受炎症影响的 MM 上方皮肤的机械刺激的逃逸阈值明显低于未受影响的大鼠。用荧光金（FG）标记来识别支配 MM 的 TRG 神经元，而用微珠（MB）来标记投射到 Vi/Vc 区域的神经元。FG/MB 标记的 TRG 神经元对 BDNF 和 trkB 呈免疫反应性（IR）。与未受影响的大鼠相比，受炎症影响的大鼠的 BDNF/trkB-IR 中小/中直径 TRG 神经元的数量明显更高。在全细胞电流钳实验中，大多数分离的小直径 TRG 神经元对 BDNF 表现出去极化反应，与尖峰放电相关，并且在炎症大鼠中，引起去极化反应的 BDNF 浓度明显更低。此外，在炎症大鼠中，电流注入期间 BDNF 诱导的尖峰数量的相对数量明显更高。BDNF 诱导的 TRG 神经元兴奋性变化被酪氨酸激酶抑制剂 K252a 消除。
本研究提供的证据表明，MM 炎症后，BDNF 增强了投射到 Vi/Vc 的小直径 TRG 神经元的兴奋性。这些发现表明，神经节 BDNF-trkB 信号是治疗三叉神经炎症性痛觉过敏的治疗靶点。
