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Plasticity and in Spinal Dorsal Horn Neuron and Neuropathic Pain : An Analysis by Patch Clamp Recordings

脊髓背角神经元的可塑性和神经性疼痛：膜片钳记录的分析

基本信息

批准号：
20591845
负责人：
KASHIBA Hitoshi
金额：
$ 2.66万
依托单位：
Kansai College of Oriental Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

The actions of neurotransmitters and modulators have well been investigated in superficial spinal dorsal horn neurons, but little is known about those in deep dorsal horn neurons. Our previous studies suggested that SP, CGRP and somatostatin play important roles in synaptic transmission to deep dorsal horn neurons. In this study, responses of SP and mENK to deep dorsal horn neurons were examined by the blind patch clamp technique used freshly sliced spinal cord of the rat (3-4weeks). About 60% of deep dorsal horn neurons in the deep lamina (III-V) showed the slow inward currents more than 5 pA by the bath application of SP (1 μM) for 1 min. These currents are considered to be evoked though G protein-Coupled SP receptors on the patched cells. Some of the recorded neurons enhanced the number and the peak amplitude of spontaneous EPSCs and/or IPSCs by the application SP. On the other hand, about 60% of the deep dorsal horn neurons showed the slow outward currents more than 5 pA by the bath application of mENK (5 μM), DAMGO (mu-receptor agonist. 1 μM), or DADLE (delta-receptor agonist; 1 μM) for 1 min. These currents are also considered to be evoked though G protein-coupled mu/delta-receptors on the patched cells. The responsive neurons to mENK always displayed the outward current by DAMGO, DADLE, or both. The amplitude of outward current was not suppressed by the repetitive application of mENK. Most of deep dorsal horn neurons with the slow inward currents by SP showed the slow outward currents by enkephalin, DAMGO, or DADLE, and vice versa. The present study suggests that about 60% of deep dorsal horn neurons receive both excitatory inputs though the NK1 receptors and inhibitory inputs though the mu-/delta-receptors.

神经递质和调质在脊髓背角浅层神经元中的作用已被广泛研究，而在脊髓背角深层神经元中的作用则知之甚少。我们前期的研究表明，SP、CGRP和生长抑素在背角深神经元的突触传递中起重要作用。本研究采用大鼠脊髓切片，用盲法膜片钳技术观察SP和mENK对脊髓背角深角神经元的反应。用SP（1 μM）浸浴1 min，约有60%的深板层背角神经元产生大于5 pA的慢内向电流，这些电流被认为是通过G蛋白偶联的SP受体诱发的。应用SP可使部分记录到的神经元自发性EPSC和/或IPSC的数量和峰值幅度增加。另一方面，在水浴应用mENK（5 μM）、DAMGO（μ-受体激动剂）后，约60%的背角神经元显示出大于5 pA的慢外向电流。1 μM）或DADLE（δ受体激动剂; 1 μM）1 min。这些电流也被认为是通过贴片细胞上的G蛋白偶联mu/δ受体诱发的。对mENK有反应的神经元总是通过DAMGO、DADLE或两者显示外向电流。重复应用mENK不抑制外向电流的幅度。大多数深背角神经元在SP作用下产生慢内向电流，在脑啡肽、DAMGO或DADLE作用下产生慢外向电流，反之亦然。目前的研究表明，大约60%的深背角神经元接受兴奋性输入通过NK 1受体和抑制性输入通过μ/δ受体。