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Research of Neural Network in Spinal Dorsal Horn and Neuropathic Pain

脊髓背角神经网络与神经病理性疼痛的研究

基本信息

批准号：
18591732
负责人：
KASHIBA Hitoshi
金额：
$ 1.72万
依托单位：
Kansai University of Health Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591732/
关键词：
Neuroscience Brain and Spinal Cord Spinal Dorsal Horn Neuropathic Pain Patch Clamp

项目摘要

Responses of membrane currents to substance P (SP) have well been examined in spinal dorsal horn neurons, but little is known about those to calcitonin gene-related peptide (CGRP) and somatostatin (STT). Therefore, we addressed these issues in freshly sliced spinal cord of rats (3-4 weeks) by using the blind patch clamp techniques.Of the dorsal horn neurons (42/68 cells) in the deep lamina (III-VI), about 60% showed the slow inward current by the bath application of SP (1 μM). These currents have been considered to be evoked though G protein-coupled SP receptors. Many of these neurons simultaneously increased excitatory post-synaptic currents (EPSCs). About 30% of deep dorsal horn neurons (12/39 cells) showed the slow inward current by the application of CGRP (1μM). The slow inward current by CGRP (n=1) was observed in the presence of tetrodotoxin (TTX, 1μM), suggesting that the currents are evoked though the G protein-coupled CGRP receptors on patched the neurons. The directly responsive neurons to CGRP always displayed the slow inward current by SP. However, the mean amplitude of these currents by CGRP was smaller than those by SP. On the other hand, the application of STT (1μM) induced the slow outward currents in about 30% of the patched deep dorsal horn neurons (9/31 cells). This outward current by STT (n=1) was also observed in the presence of tetrodotoxin (TTX, 1μM) (data not shown). Many these neurons also showed the slow inward current by SP. The slow outward currents were not suppressed by the repetitive application of STT, although the slow inward currents by SP and CGRP were desensitized.The present study suggests that CGRP and STT, in addition to SP, play important roles in synaptic transmission to deep dorsal horn neurons.

脊髓背角神经元膜电流对P物质（SP）的反应已被广泛研究，但对降钙素基因相关肽（CGRP）和生长抑素（STT）的反应却知之甚少。因此，我们在大鼠脊髓（3-4周）切片上，应用盲法膜片钳技术，在深板层（III-VI）的背角神经元（42/68个细胞）中，约60%的细胞在SP（1 μM）浴浴处理后出现慢内向电流。这些电流被认为是通过G蛋白偶联的SP受体诱发的。许多这些神经元同时增加兴奋性突触后电流（EPSC）。应用CGRP（1μM）后，约30%（12/39）的深背角神经元出现慢内向电流。在河豚毒素（TTX，1μM）存在下，观察到CGRP（n=1）的慢内向电流，提示该电流是通过贴片神经元上的G蛋白偶联CGRP受体诱发的。对CGRP有直接反应的神经元，SP均能产生慢内向电流，但其平均幅值小于SP，而STT（1μM）则能在30%（9/31）的背角神经元产生慢外向电流。在存在河豚毒素（TTX，1μM）的情况下也观察到STT（n=1）的外向电流（数据未显示）。许多神经元也显示出SP的慢内向电流，反复应用STT，虽然SP和CGRP的慢内向电流被脱敏，但慢外向电流不被抑制，提示CGRP和STT在向背角深神经元的突触传递中起重要作用。