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Research on neuronal mechanism of trigeniinal neuropathic pain in awake behaving monkeys

清醒行为猴三叉神经痛的神经机制研究

基本信息

批准号：
14571761
负责人：
IWATA Koichi
金额：
$ 1.92万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

We developed the animal model with neuropathic pain using awake behaving monkeys to evaluate the neuronal mechanism of abnormal pain sensation following peripheral nerve injury. We introduced capsaicin to monkeys as the peripheral nerve irritant topically applied to the face. First, monkeys were trained to be sitting in the monkey chair quietly for 2-3 hours. After that, monkeys were trained with thermal and light detection tasks. The thermal probe was placed on the face just lateral to the nose. When monkeys pressed the button placed in front of them, temperature shift was applied from 38 to 45-47℃ (T1) for heat trials and 30-25℃ (T1) for cold trials. After 4-8 seconds hold time, small temperature shift (T2, heat trials : 0.2-0.8℃ ; cold trials : -0.5-1.0) was coming over the T1. When monkeys detected the change in this small temperature shift, they release the button and they get reword. After completion of training of these trials, monkeys were treated with capsaicin (0.04M). One hour after capsaicin treatment, monkeys were trained with same tasks to those without capsaicin. The detection latency was significantly shorter after capsaicin treatment. The primary somatosensory cortical (SI) neuronal activity was also significantly larger in monkeys treated with capsaicin as compared with untreated normal monkeys at T1 temperature of 44℃. The relationship between detection latency and SI neuronal activity were not proportional at T1 temperature of 46-47℃. We also obtained cold sensitive neurons from SI. Cold sensitive neurons we recorded so far reduced firing frequency during performing of the cold detection tasks. These cold sensitive neurons decrease firing frequency during performing of the light detection and heat detection trials as well. These suggest that some SI neurons would be involved in the detection of the on and off-sets of the stimuli with different modalities.

我们利用清醒行为猴建立了神经病理性疼痛的动物模型，以评估周围神经损伤后异常痛感的神经机制。我们将辣椒素引入猴子，作为外周神经刺激物局部应用于面部。首先，训练猴子安静地坐在猴子的椅子上2-3个小时。在那之后，猴子接受了热和光检测任务的训练。热探头被放置在鼻子旁边的脸部。当猴子按下放在他们面前的按钮时，温度变化从38到45-47℃(T1)用于热试验，30-25℃(T1)用于冷试验。在4-8秒的保持时间后，T1上出现了较小的温度漂移(T2，热试：0.2-0.8℃；冷试验：-0.5-1.0)。当猴子探测到这个微小的温度变化时，它们会松开按钮，然后就会得到回复。在完成这些试验的训练后，猴子接受辣椒素(0.04M)治疗。在辣椒素处理一小时后，猴子接受了与不使用辣椒素的猴子相同的任务训练。辣椒素处理后，检测潜伏期明显缩短。在T1温度为44℃时，辣椒素处理的猕猴的初级体感皮层(SI)神经元的活动也显著高于未处理的正常猴子。在46~47℃的T1温度范围内，检测潜伏期与SI神经元活动不成正比。我们还从SI中获得了冷敏感神经元。到目前为止，我们记录的冷敏感神经元在执行冷检测任务时放电频率降低。这些冷敏感神经元在进行光检测和热检测试验时也会降低放电频率。这些结果表明，一些SI神经元可能参与了对不同形式刺激的开启和关闭的检测。