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Analgesia produced by cortical electrical stimulation and its modification by inhibition of NO synthase

皮质电刺激产生的镇痛及其通过抑制 NO 合酶的调节

基本信息

批准号：
10672164
负责人：
KURODA Ryotaro
金额：
$ 1.34万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672164/
关键词：
analgesia cortical stimulation pain NO synthase inhibitor c-fos antinociception secondary somatosensory cortex NO ホルマリン疼痛法

项目摘要

The primary aim of the present study was to establish an animal model in which analgesia could be produced by electrical stimulation of the secondary somatosensory cortex (S-II) that was clinically effective in a patient with intractable pain. We also wished to examine whether an inhibitor of neuronal nitric oxide (NO) synthase known to be involved in pain modulation could modify the S-II stimulation-produced analgesia.S-II stimulation failed to induce antinociception in rats, as assessed by mechanical and thermal nociception test. However, it produced notable antinociception in the formalin-induced chemical nociception test. This antinociception by S-II stimulation was potentiated by 7-nitro-indazole (7-NI), an inhibitor of neuronal NO synthase. S-II stimulation in combination with 7-NI also suppressed the formalin-induced expression of c-fos in the superficial layers of the L4 and L5 spinal dorsal horn. The antinociception evoked by S-II stimulation plus 7-NI was resistant to systemic administration of naloxone, an opioid antagonist, or of phentolamine, an α-adrenoceptor antagonist, whereas the first phase, but not second phase, antinociception was significantly inhibited by intrathecal administration of methysergide, a serotonin receptor antagonist.Our study suggests that S-II stimulation in combination with 7-NI produces strong antinociception by suppressing transmission of nociceptive information at a spinal level through activation of descending inhibitory pathways, especially serotonergic systems.

本研究的主要目的是建立一种动物模型，在该模型中，镇痛可以通过电刺激次级躯体感觉皮层（S-II），这是临床上有效的顽固性疼痛的患者产生。我们还希望研究是否已知参与疼痛调制的神经元型一氧化氮（NO）合酶抑制剂可以修改S-II刺激产生的algina.S-II刺激未能诱导大鼠的抗伤害性感受，机械和热伤害性感受试验评估。但在福尔马林化学伤害性实验中，其镇痛作用显著。7-硝基-吲唑（7-NI），神经元NO合酶的抑制剂，增强了由S-II刺激的这种抗伤害性感受。S-II刺激结合7-NI也抑制了福尔马林诱导的L4和L5脊髓背角浅层c-fos的表达。刺激S-II加7-NI引起的抗伤害性感受对全身给予阿片受体拮抗剂纳洛酮或α-肾上腺素受体拮抗剂酚妥拉明有抵抗作用，而鞘内注射麦角新碱可显著抑制第一时相的抗伤害性感受，但对第二时相无明显抑制作用，一种5-羟色胺受体拮抗剂。我们的研究表明，S-II刺激与7-羟色胺受体拮抗剂结合，NI通过激活下行抑制通路，特别是多巴胺能系统，抑制脊髓水平伤害性信息的传递，产生强烈的抗伤害性感受。