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

传入神经阻滞疼痛后三叉神经元反应和转录因子的变化

• 批准号: 10671738
• 负责人: YONEHARA Norifumi
• 金额: $ 2.11万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671738/
• 关键词: Deafferentation pain; Allodynia; Trigeminal nucleus caudalis; Nitric oxide; Inferior alveolar nerve; NMDA; 末梢神経損傷

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)

本研究旨在调查传入神经阻滞疼痛（包括异常性疼痛和痛觉过敏）的发生机制。 (1)动物模型神经病理性手术：通过拔除左上、下切牙或用铬色肠线松散结扎下牙槽神经来诱导传入阻滞疼痛。机械刺激施加在胡须和脸颊周围的皮肤表面，其感觉由三叉神经控制。作为传入神经阻滞疼痛的指标，异常性疼痛的发生由冯弗雷丝决定。神经损伤后第 7 天出现触觉异常性疼痛，并持续至少 3 周。 (2) 触觉异常性疼痛的发生机制： (1) 行为实验： 通过以剂量依赖性方式施用卡马西平、N^G-单甲基-L-精氨酸（L-NMMA；一氧化氮（NO）合酶抑制剂）和MK-801来恢复触觉异常性疼痛。 (2) 电生理实验：静脉注射引起的NO电流的变化。手术大鼠三叉神经尾核浅层同侧的 N-甲基-D-天冬氨酸 (NMDA) 和 MK801 给药量明显大于对照动物。 (3)免疫组织化学实验：测定三叉神经尾核中NO合酶(NOS)阳性神经元的数量。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。这些结果表明，牙齿周围神经损伤后出现异常性疼痛，NMDA/NO 通路可能参与触觉异常性疼痛的发生。目前我们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生。 （259字）

项目成果

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