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

本课题主要进行了两项研究：1）清醒猴实验和麻醉大鼠实验。1）为探讨三叉神经异常痛的神经机制，采用辣椒素诱发清醒猴痛敏，系统应用N型钙通道阻滞剂ONO 2921。在辣椒素处理的猴子中训练热检测任务。经口或鼻粘膜给予N型钙剂，测定热觉潜伏期。ONO 2921给药后，热检测潜伏期显著延长。与鼻给药猴相比，经口给药猴的检测潜伏期延长略长。在辣椒素未处理的猴子中，在施用ONO 2921后，我们不能观察到检测潜伏期的任何显著变化。提示ONO 2921对辣椒素引起的猴异常疼痛具有明显的镇痛作用。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痛中的作用。眶下神经（ION）损伤后，大鼠对面部机械刺激的逃避阈值降低。我们观察到，在三叉神经脊束核尾侧亚核（Vc）的神经元活动显着增强与离子结扎的大鼠。AMPA受体拮抗剂CNQX可使神经元活动明显减少，而NMDA受体拮抗剂APV或MK 801则无此作用。提示AMAP受体参与三叉神经损伤后三叉神经异常痛的发生。

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.