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)

已经进行了这项研究，以调查包括异常性疼痛和痛觉过敏在内的脱落疼痛发展的机制。 （1）动物模型的神经性手术：通过提取左上和下切牙牙齿或与铬酸肠缝合线的下牙肺炎神经的诱导诱导疼痛。机械刺激被应用在晶须和脸颊周围的皮肤表面内，其感觉由三叉神经控制。作为断开疼痛的指标，异肌的发展由冯·弗雷（Von Frey）细丝确定。触觉异常症在神经损伤后的第7天开发，至少持续了3周。 （2）开发触觉异常动物的机制：（1）行为实验：触觉异肌症是通过甲状腺齐平，N^g-摩甲基-L-精氨酸（L-NMMA； NONITRIC氧化物（NO）合成酶抑制剂）和MK-801的施用来回收的。 （2）电生理实验：i.v.诱发的无电流的改变。在手术大鼠的三叉神经核的浅表层的同侧，施用N-甲基-D-天冬氨酸（NMDA）和MK801的施用明显大于对照动物的外侧。 （3）免疫组织化学实验：在三叉神经核中测量了无合酶（NOS）阳性神经元的数量。在手术动物的两侧（同侧和对侧）的I-II和III-IV层中，NNOS阳性神经元的数量增加。这些结果表明，牙齿周围神经损伤后出现异常性疾病，NMDA/无途径可能参与触觉异常性疾病的发展。我们调查了这种触觉异常性疾病的发展涉及哪些信号转导途径和转录因子。 （259个单词）

项目成果

Takemura M., et al: "GABA (A) recoptor-mediated effects on expression of cFos in rat trigeminal mucleus following high-and low-Intensity afferent stimulation"Neuroscience. 98. 325-332 (2000)

Takemura M.等人：“高强度和低强度传入刺激后，GABA (A) 受体介导的对大鼠三叉神经核中 cFos 表达的影响”神经科学。

Takagi,J. et al.: "Serotonin receptor subtypes involved in modulation of electrical acupuncture"Jpn.J.Pharmacol.. 78. 511-514 (1998)

高木，J.

Takagi, J.and Yonehara, N.: "Serotonin receptor subtypes involved in modulation of electrical acupuncture."Jpn.J.Pharmacol.. 78. 511-514 (1998)

Takagi, J. 和 Yonehara, N.：“参与电针调节的血清素受体亚型。”Jpn.J.Pharmacol.. 78. 511-514 (1998)

Yonehara,N. et al.: "Involvement of nitric oxide in neurogenic inflammation"The Biology of Nitric Oxide, Part 6 Portland Press, London, (Moncada,S. et al eds.). 208 (1998)

米原，N.

Yoshimura M.and Yonehara N.: "Effects of topically applied capsaicin cream on neurogenic inflammation and thermal sensitivity in rats"Jpn.J.Pharmacol.. 82. 116-121 (2000)

Yoshimura M.和Yonehara N.：“局部应用辣椒素霜对大鼠神经源性炎症和热敏感性的影响”Jpn.J.Pharmacol.. 82. 116-121 (2000)