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

我们利用清醒猴建立了神经病理性疼痛动物模型，以探讨周围神经损伤后异常痛觉的神经机制。我们将辣椒素作为外周神经刺激剂局部应用于猴子的面部。首先，训练猴子安静地坐在猴椅上2-3小时。在那之后，猴子接受了热和光探测任务的训练。将热探头放置在面部上，正好在鼻子的侧面。当猴按下置于其面前的按钮时，热试验的温度从38 ℃转变为45-47℃（T1），冷试验的温度从30-25℃（T1）。4-8秒保持时间后，T1出现小的温度变化（T2，加热试验：0.2-0.8℃ ;冷却试验：-0.5-1.0 ℃）。当猴子检测到这种微小的温度变化时，它们会松开按钮，并得到重新写入。在完成这些试验的训练后，用辣椒素（0.04M）处理猴子。辣椒素处理后一小时，猴子接受与没有辣椒素的猴子相同的任务训练。辣椒素处理后的检测潜伏期明显缩短。在44℃的T1温度下，与未处理的正常猴相比，辣椒素处理的猴的初级躯体感觉皮层（SI）神经元活动也显著增加。在46-47℃的T1温度范围内，SI神经元的活动与检测潜伏期不成正比。我们还从SI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期间减少了放电频率。这些冷敏感神经元在进行光检测和热检测试验期间也降低了放电频率。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。

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.