Role of glutamate receptors to develop abnormal pain following trigeminal nerve injury in awake behaving monkeys

谷氨酸受体在清醒行为猴三叉神经损伤后产生异常疼痛的作用

基本信息

批准号：
17591952
负责人：
IWATA Koichi
金额：
$ 2.37万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591952/
关键词：
awake behaving monkey glutamate receptor neuropathic pain trigeminal nerve capsaicin N type calcium channel trigeminal spinal nucleus グルタミン酸 AMPA受容体 NMDA受容体侵害応答神経損傷単一ニューロン活動延髄熱刺激弁別行動逃避行動 N型カルシウムチャンネル TRPV1

项目摘要

Two major studies were conduced in the present project, 1) awake behaving monkey study and 2) anesthetized rat study.1) In order to evaluate the neuronal mechanisms of abnormal pain in the trigeminal region, the effect of N type calcium channel blocker, ONO 2921 was systemically applied to the awake behaving monkeys with capsaicin induced hyperalgesia. The thermal detection task was trained in capsaicin treated monkeys. N type calcium was applied orally or via nasal membrane, and the thermal detection latency was measured. Heat detection latency was significantly elongated after ONO 2921 administration. The elongation of detection latency was slightly longer in oral-administrated monkeys compared with nasal-administrated monkeys. We could not any significant change in detection latency in capsaicin-untreated monkeys after ONO 2921 administration. The present results suggest that ONO 2921 have potent ability to reduce abnormal pain following capsaicin treatment in monkeys.2) The rats' model with inferior orbital nerve injury was studied how the glutamate receptors were involved in the trigeminal neuropathic pain. Rats showed reduction of escape threshold to mechanical stimulation of the face following infra-orbital nerve (ION) injury. We observed significant enhancement of neuronal activity in the trigeminal spinal subnucleus caudalis (Vc) of the rats with ION ligation. After AMPA receptor antagonist CNQX caused significant reduction of neuronal activity in this rat, but not after NMDA receptor antagonist APV or MK801 administration. These suggest that AMAP receptor is involved in trigeminal abnormal pain following trigeminal nerve injury.

本项目进行了两项主要研究，1）清醒行为猴研究和2）麻醉大鼠研究。1）为了评估三叉神经区异常疼痛的神经机制，N型钙通道阻滞剂ONO的作用2921被系统性地应用于患有辣椒素引起的痛觉过敏的清醒行为猴子。热检测任务是在经过辣椒素处理的猴子身上进行的训练。口服或鼻粘膜施用N型钙，并测量热检测潜伏期。 ONO 2921 给药后发情检测潜伏期显着延长。与鼻腔给药的猴子相比，口服给药的猴子的检测潜伏期的延长稍长。在未接受辣椒素治疗的猴子中，给予 ONO 2921 后，我们未能发现检测潜伏期有任何显着变化。目前的结果表明，ONO 2921 具有有效减轻猴子辣椒素治疗后异常疼痛的能力。2) 大鼠眼眶下神经损伤模型研究了谷氨酸受体如何参与三叉神经病理性疼痛。眶下神经（ION）损伤后，大鼠对面部机械刺激的逃避阈值降低。我们观察到 ION 结扎大鼠三叉神经脊髓尾核亚核 (Vc) 的神经元活性显着增强。 AMPA 受体拮抗剂 CNQX 导致该大鼠神经元活性显着降低，但在 NMDA 受体拮抗剂 APV 或 MK801 给药后则没有。这些表明AMAP受体参与三叉神经损伤后的三叉神经异常疼痛。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ca^<2+>/ calmodulin-protein kinase IIα in the trigeminal subnucleus caudalis contributes to neuropathic pain following inferior alveolar nerve transaction.

三叉神经尾部亚核中的Ca 2+ /钙调蛋白蛋白激酶IIα导致下牙槽神经交易后的神经性疼痛。

DOI：
发表时间：
2005
期刊：
Experimental Neurology 192(2)
影响因子：
0
作者：
Kondo;S.;et al.;Kitagawa J;Kondo S et al.;Kondo S. et al.;Yosimichi G. et al.;Ogawa A
通讯作者：
Ogawa A

Differential responses of rostral subnucleus caudalis nad upper cervical dorsal neurons to mechanical and chemical stimulation of the parotid gland in rats.

大鼠尾侧喙亚核和上颈背神经元对腮腺机械和化学刺激的差异反应。

DOI：
发表时间：
2006
期刊：
Brain Research 1106(1)
影响因子：
0
作者：
Tokita;K;Inoue T.;Nakamichi Y et al.;Nakamichi Y et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Takahashi N et al.;Okumura S et al.;Mizoguchi T;Kobayashi Y;Kobayashi Y;Yang S;Take I;Tsuboi H;Takahashi N et al.;松本歯科大学大学院硬組織研究グループ;Nakajima A.;Kubota I.;Suzuki I.;Nobutaka Haramoto;Kubota I;Tetsuya Kawane;Suzuki I;Shimizu K.;Ogawa A.
通讯作者：
Ogawa A.

Activation of trigeminal intranuclear pathway in rats with TMJ inflammation.

颞下颌关节炎症大鼠三叉神经核内通路的激活。

DOI：
发表时间：
2005
期刊：
Journal of Oral Science 47(2)
影响因子：
0
作者：
Yosimichi;G.;et al.;Sato T.
通讯作者：
Sato T.

Phosphorylation of ERK in the trigeminal spinal nucleus neurons following passive jaw movement in the rats with chronic craniomandibular joint inflammation.

慢性颅下颌关节炎症大鼠被动下颌运动后三叉神经脊神经元中 ERK 的磷酸化。

DOI：
发表时间：
2007
期刊：
Journal of Orofacial Pain (in press)
影响因子：
0
作者：
Tokita;K;Inoue T.;Nakamichi Y et al.;Nakamichi Y et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Takahashi N et al.;Okumura S et al.;Mizoguchi T;Kobayashi Y;Kobayashi Y;Yang S;Take I;Tsuboi H;Takahashi N et al.;松本歯科大学大学院硬組織研究グループ;Nakajima A.;Kubota I.;Suzuki I.
通讯作者：
Suzuki I.

Mechanisms involved in modulation of trigeminal primary afferent activity in rats with peripheral mononeuropathy