Role of paracrine mechanism on the excitability of trigeminal root ganglion following temporomandibular joint disorder

本研究旨在探讨颞下颌关节（TMJ）炎症后，支配TMJ的三叉神经根节（TRG）神经元局部释放P物质（SP）是否通过旁分泌机制调节支配面部皮肤的Aβ-TRG神经元的兴奋性。将完全弗氏佐剂（CFA）注射到大鼠TMJ中以产生炎症。为了比较正常大鼠和炎症大鼠SP反应性的差异，我们采用行为学（机械刺激阈值）、电生理学（膜片钳/细胞外离子导入记录TRG神经元）、分子学（NK 1 mRNA）和免疫组织化学（SP/NK 1受体功能蛋白）方法进行了以下实验。颞下颌关节炎大鼠逃避机械刺激的阈值显著降低。炎症组大鼠颞下颌关节SP免疫反应阳性神经元数量明显多于对照组， ...更多信息 的增加。在皮肤中直径和大直径TRG神经元（>30μm）中，SP（100 nM）诱导的膜去极化在炎症大鼠中的发生率大于未炎症大鼠。定量单细胞逆转录-聚合酶链反应分析显示，在发炎大鼠皮肤TRG神经元的NK 1受体mRNA的表达增加。SP/NK 1受体/神经丝200阳性神经元数量在炎症大鼠皮肤TRG中显著增加。炎症大鼠Aβ-TRG神经元的机械刺激阈值明显低于正常大鼠。电离子导入NK 1受体拮抗剂后，未处理大鼠和炎症大鼠的机械刺激阈值无显著差异。这些结果表明，颞下颌关节炎症可改变支配面部皮肤的Aβ-TRG神经元的兴奋性，其索马胞体中SP /NK 1受体的增加可能有助于颞下颌关节疾病中三叉神经炎性异常性疼痛的机制。少

The aim of the present study to investigate whether the local release of substance P (SP) from the trigeminal root ganglion (TRG) neurons innervating temporomandibular joint (TMJ) modulates the excitability of Aβ-TRG neurons innervating the facial skin via the paracrine mechanism, in rats after TMJ inflammation. Complete Freund's adjuvant (CFA) was injected into the rat TMJ to produce inflammation. To compare the difference of SP responsiveness between naive and inflamed rats, we have conducted following experiments by using behavioral (mechanical stimulation threshold), electrophysiological (patch-clamp / extracellular recording with iontophoretic application for TRG neurons), molecular (mRNA for NK1) and immunohistochemical (functional protein for SP/NK1 receptor) approaches. The threshold for escape from mechanical stimulation applied to the orofacial area in TMJ-inflamed rats was significantly decreased. The number of SP-immunoreactive TMJ neurons in the inflamed rats was significa … More ntly increased. In cutaneous medium- and large-diameter TRG neurons (>30μm), the occurrence of SP (100nM) induced membrane depolarization in inflamed rats was larger than that in the naive rats. Quantitative single-cell reverse transcription-polymerase chain reaction analysis showed the increased expression of mRNA for NK1 receptor in cutaneous TRG neurons in inflamed rats. The numbers of SP/NK1 receptors / neurofilament 200 positive cutaneous TRG neurons in the inflamed rats were significantly increased. The mechanical stimulation threshold of Aβ-TRG neurons in inflamed rats was significantly lower than that in naive rats. There were no significant differences on the mechanical stimulation threshold between naive and inflamed rats after iontophoretic application of NK1 receptor antagonists. These results suggest that TMJ inflammation can alter the excitability of Aβ-TRG neurons innervating the facial skin, and that an increase in SP / NK1 receptors in their soma may contribute to the mechanism underlying the trigeminal inflammatory allodynia in the TMJ disorder. Less