Study on the role of the primary afferent fibers in thedevelopment/maintenance of the intractable pain in the oro-facial region

众所周知，神经损伤或慢性炎症后可出现异常性疼痛、痛觉过敏、幻肢痛等病理性疼痛状态。我们也认识到，来自受损神经区域的传入脉冲流的增加增强了脊髓背角神经元的活动并产生疼痛。脊髓背角神经元n -甲基- d -天冬氨酸（NMDA）受体的激活被广泛认为是神经损伤引起的痛觉过敏发生和维持的关键。越来越多的证据表明，n -甲基- d -天冬氨酸（NMDA）受体的激活通过一氧化氮（NO）途径调节伤害性传递。因此，为了进一步阐明周围神经损伤引起的三叉神经系统病理性疼痛的中枢机制，本项目研究了NO对下牙槽神经结扎损伤后脑干三叉神经感觉核复合体（SpVc-I， II）尾侧亚核浅层兴奋性氨基酸（eaa）水平变化的影响。结扎动物与假手术大鼠相比，在灌注开始后立即观察到非常高的EAAs释放反应。结扎动物用40 v牙髓刺激或1%辣椒素乳膏诱发的EAA水平明显高于假手术动物。在灌注液中加入NO清除剂羧基ptio可抑制辣椒素乳膏诱导的EAAs水平升高。这些结果表明，刺激引起的EAA水平升高的改变发生在牙痛通路的第一突触中继部位，并通过内源性NO表达，在牙周围神经损伤后病理疼痛状态的发展和/或维持中起重要作用

It is well known that the pathological pain states such as allodynia, hyperalgesia, and phantom pain can result after nerve injury or chronic inflammation. It is also recognized that an increase in the afferent impulse flow from damaged nerve areas enhances the activity of spinal dorsal horn neurons and produces pain. The activation of N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horn neurons is widely regarded to be critical for the development and maintenance of the hyperalgesia induced by nerve injury.Increasing evidence suggests that, at the site of the first synaptic relay of nociceptive pathway, activation of N-methyl-D-aspartate (NMDA) receptors modulates nociceptive transmission via a nitric oxide (NO) pathway. Therefore, to further clarify the central mechanisms underlying the peripheral nerve injury-induced pathological pain in the trigeminal system, this project examined influence of NO to the change in excitatory amino acids (EAAs) level in the superficial layer of subnucleus caudalis of the brain-stem trigeminal sensory nuclear complex (SpVc-I, II) following a ligation injury to the inferior alveolar nerves.A very high EAAs release responses was observed immediately after the start of the perfusion in ligated animals compared with sham-operated rats. The EAA level evoked by application of the 40-V tooth pulp-stimulation or 1% capsaicin cream was significantly higher in the ligated animals than those in the sham-operated animals. This increase of EAAs level induced by capsaicin cream was inhibited by adding carboxy-PTIO, an NO scavenger, to the perfusate.These results suggest that alterations in the stimulus-evoked raised EAA levels that occur in the site of the first synaptic relay of the dental pain pathway and which are expressed via endogenous NO, and which play an important role in development and/or maintenance of pathological pain states following dental peripheral nerve injury