Alterations of neuronal response and transcription factors in the trigeminal nucleus following deafferentation pain

本研究旨在探讨包括异位性痛觉和痛觉过敏在内的神经脱突性疼痛的发生机制。(1)动物模型的神经性手术：通过拔除左上、下切牙或用铬肠缝线松散结扎下牙槽神经来诱导脱神经痛。在胡须和脸颊周围的皮肤表面施加机械刺激，其感觉由三叉神经控制。异位性疼痛的发展以von Frey纤维为指标，作为脱神经递质疼痛的指标。触觉异常性痛发生于神经损伤后第7天，并持续至少3周。(2)触觉异常性痛发生机制：(1)行为实验：以卡马西平、N^ g -单甲基- l-精氨酸（L-NMMA，一氧化氮（NO）合成酶抑制剂）和MK-801剂量依赖的方式治疗触觉异常性痛。(2)电生理实验：手术大鼠三叉神经尾核浅层同侧静脉注射n -甲基- d -天冬氨酸（NMDA）和MK801引起的NO电流变化明显大于对照组。(3)免疫组化实验：测定三叉神经尾核NO合成酶（NOS）阳性神经元数量。手术动物两侧（同侧和对侧）I-II层和III-IV层nnos阳性神经元数量增加。这些结果提示，牙周神经损伤后发生了触觉异常性痛，NMDA/NO通路可能参与了触觉异常性痛的发生。目前，我们正在研究哪些信号转导途径和转录因子参与了这种触觉异常性疼痛的发展。(259字)

This study has been conducted to investigate the mechanisms of development of deafferentation pain including allodynia and hyperalgesia. (1) Neuropathic surgery for animal model : The induction of deafferentation pain was achieved by extraction of the left upper and lower incisor teeth or loose ligation of the inferior alveolar nerve with a chromic gut suture. Mechanical stimulation was applied within the surface of skin around whisker and cheek, sensory of which is controlled by the trigeminal nerves. As an indicator of deafferentation pain, the development of allodynia was determined by von Frey filaments. Tactile allodynia developed by day 7 after the nerve injury and lasted for at least 3 weeks. (2) Mechanisms on development of tactile allodynia : (1) Behavioral experiment : Tactile allodynia was recovered by administration of carbamazepine, N^G-monomethyl-L-arginine (L-NMMA ; nitric oxide (NO) synthase inhibitor) and MK-801 in dosedependent manner. (2) Electrophysiological experiment : The alteration of NO current evoked by the i.v. administration of N-methyl-D-aspartate (NMDA) and MK801 was significantly larger in the ipsilateral side of the superficial layers of the trigeminal nucleus caudalis of operated rats than that of control animals. (3) Immunohistochemical experiment : The number of NO synthase (NOS)-positive neurons were measured in the trigeminal nucleus caudalis. The number of nNOS-positive neurons increased in the layers I-II and III-IV in both side (ipsilateral and contralateral) of operated animals. These results suggest that allodynia developed following dental peripheral nerve injury, and NMDA/NO pathways may be involved in development of tactile allodynia. Crrently we investigate what signal transduction pathways and transcription factors are involved in development of such tactile allodynia. (259 words)