Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain
Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain
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支配口面部区域的三叉神经节神经元中的酸敏感离子通道导致口面部炎性疼痛。
DOI：
10.1111/1440-1681.12510
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发表时间：
2016-02-01
影响因子：
2.9
通讯作者：
Hu, Zhuang-Li
中科院分区：
文献类型：
--
作者：
Fu, Hui;Fang, Peng;Hu, Zhuang-Li
口面疼痛是一种常见的临床症状，伴有牙痛、偏头痛和牙龈炎。越来越多的证据表明，酸敏感离子通道（ASICs），特别是ASIC3，可以深刻地影响外周感觉神经元的伤害感受的生理特性。本研究的目的是研究三叉神经节（TG）神经元中的ASIC在口面部炎性疼痛中的作用。进行了Western blot（WB）、标记三叉神经节神经元的免疫荧光分析、口面福尔马林试验、细胞制备和电生理实验。本研究表明，ASIC1，ASIC2a和ASIC3高表达的TG神经元支配的口面区域。在福尔马林诱导的口面部炎性痛模型中，这些神经元的ASIC电流幅度增加119.72%（ASIC1样电流）和230.59%（ASIC3样电流）。WB和免疫荧光检测结果显示，与对照组相比，口面炎症过程中口面TG神经元中ASICs的表达显著增加。ASIC1、ASIC2a和ASIC3的相对蛋白密度也分别比对照组增加58.82 ± 8.92%、45.30 ± 11.42%和55.32 ± 14.71%。此外，ASICs的药理学阻断和ASIC1的基因缺失减弱了炎症反应。这些发现表明，外周炎症可诱导TG神经元中ASICs的上调，引起口面部炎性疼痛。此外，ASIC的特异性抑制剂可能对口面部炎性疼痛具有显著的镇痛作用。
Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 +/- 8.92%, 45.30 +/- 11.42% and 55.32 +/- 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain.