Involvement of NMDA–nitric oxide pathways in the development of tactile hypersensitivity evoked by the loose-ligation of inferior alveolar nerves in rats
Involvement of NMDA–nitric oxide pathways in the development of tactile hypersensitivity evoked by the loose-ligation of inferior alveolar nerves in rats
复制标题
DOI：
10.1016/s0006-8993(02)03983-5
复制
发表时间：
2003-02
期刊：
影响因子：
2.9
通讯作者：
N. Yonehara;Chiho Kudo;Y. Kamisaki
中科院分区：
文献类型：
--
作者：
N. Yonehara;Chiho Kudo;Y. Kamisaki
为了研究三叉神经系统中的NMDA/一氧化氮（NO）通路是否参与牙科手术后观察到的痛觉过敏和异常性疼痛等病理性疼痛状态的发展和/或维持，对大鼠左下牙槽神经进行松结扎。然后使用von Frey细丝测量对机械刺激的反应。术后5天结扎动物的同侧出现触觉刺激超敏反应，并持续至少30天。此外，还研究了手术后2 - 3周期间药物对这些疼痛状态的影响。结果，观察到触觉超敏性被腹膜内（i.p.）lmg/kg）和NG-单甲基-1-精氨酸乙酸酯（I-NMMA：10 - 100mg/kg）。此外，NO的生产和神经元NO合酶（nNOS）阳性神经元在三叉神经尾侧核（SpVc）的数量进行了评价。作为这些实验的结果，发现与假手术大鼠相比，在松结扎大鼠中，通过静脉输注N-甲基-d-天冬氨酸（NMDA; 10 mg/kg）和MK-801（0.5 mg/kg）诱发的NO水平变化显著更大。此外，nNOS阳性神经元的数量被发现有增加的同侧在I/II层的SpVc。这些结果表明，触觉超敏性发展后，下齿槽神经损伤和NMDA受体/NOS/NO生产途径的SpVc可能参与这种病理生理状态的发展。
To investigate whether or not NMDA/nitric oxide (NO) pathways in the trigeminal system are involved in the development and/or maintenance of such pathological pain states as the hyperalgesia and allodynia observed after dental surgery, loose-ligation on the left inferior alveolar nerves of rats were performed. The responses to mechanical stimulation were then measured using von Frey filaments. Hypersensitivity to tactile stimulation developed on the ipsilateral side in ligated animals 5 days after surgery and lasted for at least 30 days. In addition, the effects of drugs on these pain states during the period 2–3 weeks following surgery were investigated. As a result, it was observed that tactile hypersensitivity was inhibited by the intraperitoneal (i.p.) administration of both MK-801 hydrogen maleate (0.05–0.1 mg/kg) and NG-monomethyl-l-arginine acetate (l-NMMA: 10–100 mg/kg). Still further, NO production and the number of neuronal NO synthase (nNOS)-positive neurons in the trigeminal nucleus caudalis (SpVc) was evaluated. As a result of these experiments, it was found that the changes in NO levels evoked by the intravenous infusions of N-methyl-d-aspartate (NMDA; 10 mg/kg) and MK-801 (0.5 mg/kg) were significantly larger in the loose-ligated rats compared to the sham-operated rats. Moreover, the number of nNOS-positive neurons was found to have increased on the ipsilateral side in layers I/II of the SpVc. These results would suggest that tactile hypersensitivity develops after inferior alveolar nerve injury and that NMDA receptor/NOS/NO production pathways in the SpVc may be involved in the development of such pathophysiological states.