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The study of the pain mechanisms using rat dorsal root ganglia

大鼠背根神经节疼痛机制的研究

基本信息

批准号：
17591656
负责人：
MINAMI Koucihiro
金额：
$ 2.35万
依托单位：
Jichi Medical University (2006-2007)University of Occupational and Environmental Health, Japan (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591656/
关键词：
pain Ion channel G protein Coupled Receptor Volatile Anesthetics Dorsal root ganglia Xenopus oocytes Alohaxalone Pain mechanism イオンチャンネルサブスタンスP受容体抗侵害作用麻酔薬鎮痛薬パッチクランプ法エタノール

项目摘要

The dorsal root ganglion (DRG) neurons and associated primary afferent nerves transmit different sensory modalities, including nociception, to the spinal dorsal horn. Many types of neuronal cell have been found on primary afferent neurons, either on their central or peripheral processes or on the cell bodies of DRG cells and the presence of several GPCRs has been reported, including substance P, muscarinic, 5-HT_2 and orexin receptors. Consequently, the DRG has been used to study nociception. It is of interest to determine drug actions on these receptors, and we investigated the role of the glutamate receptor in DRG and the effects of anesthetics on the function of mGluR1 and mGluR5 expressed in Xenopus laevis oocytes. We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on SP-induced currents mediated by SPR expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the volatile anesthetics tested, and ethanol, inhibited SPR-induced Ca(2+ … More )-activated Cl(-) currents at pharmacologically relevant concentrations. Neurosteroid, alphaxalone, inhibited the acetylcholine (Ach)-mediated responses of M(1) and M(3) receptors expressed in Xenopus oocytes, whereas DHEA did not. Moreover, we examined the the effects of Dexmedetomidine in this systems. Dexmedetomidine did not affect the 5-HT_2c-, substance P-, or orexin A-induced Cl^- currents in oocytes expressing the respective receptors. The compound also had little effect on the acetylcholine (Ach, 1μM)-induced Ca^<2+>-activated C1^- currents in Xenopus oocytes expressing M_1 receptors. In contrast, dexmedetomidine inhibited the Ach-induced currents in Xenopus oocytes expressing M_3 receptors. Dexmedetomidine reduced the Ach-induced C1^- currents after treatment with the selective protein kinase C inhibitor GF109203X. Moreover, the compound inhibited the muscarinic receptor-mediated increases in [Ca^<2+>; in cultured DRG cells in a concentration-dependent manner. From these results, the glutamate receptors may play the important role in pain transmission in DRG. Less

背根神经节 (DRG) 神经元和相关的初级传入神经将不同的感觉方式（包括伤害感受）传递到脊髓背角。在初级传入神经元上发现了许多类型的神经元细胞，无论是在它们的中枢或外周突上，还是在 DRG 细胞的细胞体上，并且已报道了几种 GPCR 的存在，包括 P 物质、毒蕈碱、5-HT_2 和食欲素受体。因此，DRG 已被用于研究伤害感受。确定药物对这些受体的作用很有意义，我们研究了谷氨酸受体在 DRG 中的作用以及麻醉剂对非洲爪蟾卵母细胞中表达的 mGluR1 和 mGluR5 功能的影响。我们使用全细胞电压钳检查了氟烷、异氟烷、安氟烷、乙醚和乙醇对爪蟾卵母细胞中表达的 SPR 介导的 SP 诱导电流的影响。所有测试的挥发性麻醉剂和乙醇均在药理学相关浓度下抑制 SPR 诱导的 Ca(2+ … 更多) 激活的 Cl(-) 电流。神经类固醇 alphaxalone 可抑制爪蟾卵母细胞中表达的 M(1) 和 M(3) 受体的乙酰胆碱 (Ach) 介导的反应，而 DHEA 则不然。此外，我们还检查了右美托咪定在该系统中的作用。右美托咪定不影响表达各自受体的卵母细胞中5-HT_2c-、物质P-或食欲素A诱导的Cl^-电流。该化合物对表达M_1受体的爪蟾卵母细胞中乙酰胆碱(Ach，1μM)诱导的Ca 2+ 激活的C1 电流也几乎没有影响。相反，右美托咪定抑制表达 M_3 受体的非洲爪蟾卵母细胞中 Ach 诱导的电流。用选择性蛋白激酶 C 抑制剂 GF109203X 治疗后，右美托咪定可减少 Ach 诱导的 C1^- 电流。此外，该化合物抑制毒蕈碱受体介导的[Ca 2+ ； ] 增加。在培养的 DRG 细胞中以浓度依赖性方式。从这些结果来看，谷氨酸受体可能在 DRG 的疼痛传递中发挥重要作用。较少的