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

本研究旨在探讨去传入性疼痛的发生机制，包括痛觉超敏和痛觉过敏。(1)神经外科动物模型：采用拔除左上、下切牙或松解下牙槽神经铬线结扎的方法诱导去传入性疼痛。机械刺激位于胡须和面颊周围的皮肤表面，其感觉由三叉神经控制。作为去传入性疼痛的一个指标，von Frey细丝决定了痛觉异常的发展。神经损伤后7d开始出现触觉超敏，并持续至少3周。(2)触觉超敏的发生机制：(1)行为学实验：给予卡马西平、N^G-单甲基-L-精氨酸(N^G-单甲基-L-精氨酸；一氧化氮合酶抑制剂)和MK-801以剂量依赖的方式恢复触觉超敏。(2)电生理实验：静脉注射诱发的NO电流变化。手术组大鼠同侧三叉神经尾侧核浅层注射N-甲基-D-天冬氨酸(NMDA)和MK801的量明显大于对照组。(3)免疫组织化学实验：检测三叉神经尾侧核内一氧化氮合酶(NOS)阳性神经元的数量。手术组大鼠双侧(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，牙齿周围神经损伤后发生了痛觉异常，NMDA/NO通路可能参与了触觉痛觉异常的发生。目前，我们研究了哪些信号转导途径和转录因子参与了这种触觉异常痛觉的发生。(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)