Role of glutamate receptors to develop abnormal pain following trigeminal nerve injury in awake behaving monkeys

为探讨三叉神经区异常疼痛的神经机制，本课题系统地应用了N型钙通道阻滞剂ONO 2921对辣椒素诱发的觉醒行为猴痛觉过敏的影响。热检测任务是在辣椒素处理的猴子身上进行的训练。口服或经鼻膜注入N型钙，测量热探测潜伏期。Ono2921给药后热检测潜伏期明显延长。与鼻腔给药的猴子相比，口服给药的猕猴检测潜伏期的延长略长一些。Ono 2921给药后，未经辣椒素处理的猴子的检测潜伏期没有任何显著变化。本研究结果提示，ONO 2921对辣椒素治疗猴的异常疼痛有较强的抑制作用。2)建立大鼠眶下神经损伤模型，研究谷氨酸受体在三叉神经病理性疼痛中的作用。在眶下神经损伤后，大鼠对面部机械刺激的逃避阈值降低。我们观察到离子结扎大鼠三叉神经脊束核尾侧亚核(Vc)神经元活动明显增强。在AMPA受体拮抗剂CNQX引起大鼠神经元活性显著降低后，NMDA受体拮抗剂APV或MK801给药后无明显变化。提示AMAP受体参与了三叉神经损伤后三叉神经痛的发生。

Two major studies were conduced in the present project, 1) awake behaving monkey study and 2) anesthetized rat study.1) In order to evaluate the neuronal mechanisms of abnormal pain in the trigeminal region, the effect of N type calcium channel blocker, ONO 2921 was systemically applied to the awake behaving monkeys with capsaicin induced hyperalgesia. The thermal detection task was trained in capsaicin treated monkeys. N type calcium was applied orally or via nasal membrane, and the thermal detection latency was measured. Heat detection latency was significantly elongated after ONO 2921 administration. The elongation of detection latency was slightly longer in oral-administrated monkeys compared with nasal-administrated monkeys. We could not any significant change in detection latency in capsaicin-untreated monkeys after ONO 2921 administration. The present results suggest that ONO 2921 have potent ability to reduce abnormal pain following capsaicin treatment in monkeys.2) The rats' model with inferior orbital nerve injury was studied how the glutamate receptors were involved in the trigeminal neuropathic pain. Rats showed reduction of escape threshold to mechanical stimulation of the face following infra-orbital nerve (ION) injury. We observed significant enhancement of neuronal activity in the trigeminal spinal subnucleus caudalis (Vc) of the rats with ION ligation. After AMPA receptor antagonist CNQX caused significant reduction of neuronal activity in this rat, but not after NMDA receptor antagonist APV or MK801 administration. These suggest that AMAP receptor is involved in trigeminal abnormal pain following trigeminal nerve injury.