Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats
Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats
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DOI：
10.1053/j.gastro.2008.01.031
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发表时间：
2008-04-01
期刊：
影响因子：
29.4
通讯作者：
Noguchi, Koichi
中科院分区：
文献类型：
--
作者：
Sakurai, Jun;Obata, Koichi;Noguchi, Koichi
背景与目的：内脏感觉神经元特性的改变参与了胃肠道疼痛的发生。然而，很少有人知道的分子参与机械感觉从胃肠道。本实验研究了伤害性胃扩张（GD）对大鼠背根神经节（DRG）和结状神经节（NG）细胞外信号调节激酶1/2（ERK 1/2）磷酸化的影响及其在急性内脏痛中的作用。研究方法：在内脏神经切除或迷走神经切断后的大鼠和对照组大鼠的肩峰肌记录了经胃造口胃球囊扩张的肌电反应。然后我们用免疫组织化学方法检测GD后DRG和NG中磷酸化ERK 1/2（p-ERK 1/2）的标记。结果：胃扩张可诱导DRG和NG神经元p-ERKI/2表达，峰值出现在刺激后2 min。我们发现，刺激强度依赖性增加的激活神经元的数量，这种激活对应的内脏反应的发病率。这些p-ERK 1/2标记的神经元大多数是小型和中型神经元，共表达瞬时受体电位香草酸1离子通道和酸敏感离子通道3。内脏神经切除，而不是迷走神经切断，影响内脏反应，并减弱ERK 1/2激活的DRG神经元产生的GD。此外，鞘内给药的丝裂原活化蛋白激酶激酶1/2抑制剂，U 0126，改变了对有害的GD的反应。结论：伤害性GD对DRG神经元ERK 1/2通路的激活可能与功能活动有关，并可能参与急性内脏痛。
Background & Aims: Changes in the properties of visceral sensory neurons contribute to the development of gastrointestinal pain. However, little is known about the molecules involved in mechanosensation from the gastrointestinal tract. We investigated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase cascade, in dorsal root ganglion (DRG) and nodose ganglion (NG) neurons by noxious gastric distention (GD) and its involvement in acute visceral pain in rats. Methods: Electromyographic responses to gastric balloon distention through gastrostomy were recorded from the acro-miotrapezius muscle in rats after splanchnic nerve resection or vagotomy and in control rats. We then examined the phosphorylated-ERK1/2 (p-ERK1/2) labeling in the DRG and NG after GD using immunohistochemistry. Results: Gastric distention induced p-ERKI/2 in DRG and NG neurons with a peak at 2 minutes after stimulation. We found a stimulus intensity-dependent increase in the number of activated neurons, and this activation corresponded well with the incidence of the visceromotor response. Most of these p-ERK1/2-labeled neurons were small- and medium-sized neurons that coexpressed transient receptor potential vanilloid 1 ion channel and acid-sensing ion channel 3. Splanchnic nerve resection, but not vagotomy, affected the visceromotor response, and attenuated the ERK1/2 activation in DRG neurons produced by GD. Furthermore, intrathecal administration of the mitogen-activated protein kinase kinase 1/2 inhibitor, U0126, altered the response to noxious GD. Conclusions: The activation of ERK1/2 pathways in DRG neurons by noxious GD may be correlated with functional activity, and may be involved in acute visceral pain.