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STUDY ON CORTICAL STIMULATION-EVOKED ANALGESIA IN PERSISTENT PAIN MODELS

持续性疼痛模型中皮质刺激诱发镇痛的研究

基本信息

批准号：
12672233
负责人：
KURODA Ryotaro
金额：
$ 1.28万
依托单位：
KINKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

The aim of the study was to establish novel animal models in which electrical stimulation of cortical Sll area, known to be clinically analgesic, is capable of producing potent antinociception.1. Sll stimulation-evoked antinociception in the formalin-induced nociception model : Stimulation electrodes were chronically implanted into the Sll area of the rat. The formalin-induced nociceptive behavior and expression of Fos in the superficial layer of the dorsal horn was slightly reduced by Sll stimulation. Sll stimulation in combination with 7-nitro indazole, a neuronal NO synthase inhibitor, produced strong antinociception and suppression of Fos expression. The effect of Sll stimulation was partially blocked by intrathecal administration of methysergide, a serotonin receptor antagonist, suggesting involvement of the descending serotonin neurons.2. PAR-2-triggered nociception model and its characterization : Stimulation of PAR-2 expressed in the peripheral terminal of C-fiber triggered thermal hyperalgesia, nociceptive behavior and expression of spinal Fos. The nociceptive processing by PAR-2 was characterized in the present study.3. Effect of Sll stimulation in the PAR-2-mediated nociception model and the surgically prepared neuropathy model : Sll stimulation failed to exhibit any antinociceptive activity in these two models.Further effort will be necessary to establish models in which Sll stimulation is highly analgesic.

这项研究的目的是建立一种新的动物模型，在这种动物模型中，对临床已知具有镇痛作用的皮质Sll区域进行电刺激，能够产生有效的抗炎药。在福尔马林诱导的伤害感觉模型中，Sll刺激诱发的抗伤害感觉：刺激电极长期植入大鼠Sll区域。福尔马林诱导的痛觉行为和背角浅层Fos的表达在Sll刺激下略有降低。Sll刺激联合7-硝基茚唑（一种神经元NO合成酶抑制剂）可产生较强的抗伤性和抑制Fos表达。5 -羟色胺受体拮抗剂methysergide的鞘内注射可部分阻断Sll刺激的效果，提示下行5 -羟色胺神经元参与其中。PAR-2触发痛觉模型及其表征：刺激c -纤维外周末端表达的PAR-2触发热痛觉过敏、痛觉行为和脊髓Fos的表达。本研究对PAR-2的伤害性加工进行了表征。Sll刺激在par -2介导的伤害感觉模型和手术准备的神经病变模型中的作用：Sll刺激在这两种模型中均未表现出任何抗伤害感觉活性。需要进一步的努力来建立Sll刺激具有高度镇痛作用的模型。