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Trigeminal Neuropathic Pain Mechanisms

三叉神经病理性疼痛机制

基本信息

批准号：
7091427
负责人：
MICHAEL A HENRY
金额：
$ 22.81万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7091427
关键词：
afferent nerve behavior test carbamazepine chronic pain electron microscopy histochemistry /cytochemistry ion channel blocker laboratory rat light microscopy nerve injury neuropathology nociceptors sodium channel trigeminal nerve trigeminal neuralgia

项目摘要

DESCRIPTION (provided by applicant): Chronic neuropathic pain can be a devastating disease and the management is often inadequate. A recent focus of pain research is examining changes in the expression of sodium channels that follow nerve injury since these changes may contribute to neuronal hyperexcitability and the development of neuropathic pain. This proposal will investigate the distributions of Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 sodium channel isoforms at both the light and electron microscopic levels in normal rat trigeminal primary afferents (infraorbital nerve, trigeminal ganglion/root entry zone and trigeminal sensory nucleus) and in intrinsic neurons in the trigeminal sensory nucleus. Once the normal expression is determined for each isoform, then changes in this expression will be evaluated in the same regions following a chromic suture injury to; 1) infraorbital nerve, or 2) trigeminal root entry zone, combined with behavioral testing for altered nociception. The hypothesis is that there will be a change in the normal distribution of the sodium channel isoforms following injury that correlates with behavioral evidence for altered nociception, the changes may depend on the site of the injury (peripheral vs. central), these changes contribute to neuronal hyperactivity of both primary afferents and intrinsic neurons seen following lesions, and the reduction of hyperexcitability with sodium channel blocking drugs. The trigeminal system represents an excellent model system to evaluate differences in sodium channel expression following either peripheral nerve or central root injury since distinct clinical entities are seen in humans following these different injuries. Trigeminal neuralgia may result from a root entry zone injury, while peripheral trigeminal neuropathy follows damage to peripheral nerves. There may be a difference in the expression of sodium channels following peripheral and central injury, since patients with trigeminal neuralgia usually respond to carbamazepine, while patients with peripheral trigeminal neuropathy rarely obtain significant relief with only carbamazepine. A differential expression of sodium channels in different fiber types may also be responsible for the different clinical characteristics of pain seen following peripheral and central injury. Identification of specific sodium channel alterations after injury may help develop more selective treatments for neuropathic pain.

描述(申请人提供)：慢性神经性疼痛可以是一种毁灭性的疾病，管理往往是不充分的。最近疼痛研究的一个焦点是检测神经损伤后钠通道表达的变化，因为这些变化可能有助于神经元的过度兴奋和神经病理性疼痛的发展。本研究将从光镜和电子显微镜水平研究正常大鼠三叉神经初级传入神经(眶下神经、三叉神经节/根进入区和三叉神经感觉核)和三叉神经感觉核内固有神经元中钠离子通道亚型Nav1.1、Nav1.2、Nav1.3、Nav1.6、Nav1.7、Nav1.8和Nav1.9。一旦确定了每个亚型的正常表达，则将在以下相同区域评估该表达的变化：1)眶下神经，或2)三叉神经根进入区，结合伤害性感觉改变的行为学测试。假设损伤后钠通道亚型的正常分布将发生变化，这与伤害性感受改变的行为学证据相关，这种变化可能取决于损伤的位置(外周和中枢)，这些变化导致损伤后初级传入和内源性神经元的神经元过度活动，以及钠通道阻断药物降低超兴奋性。三叉神经系统是评估外周神经或中枢神经损伤后钠通道表达差异的极好的模型系统，因为在这些不同的损伤后，人类可以看到不同的临床实体。三叉神经痛可能由根进入区损伤引起，而周围三叉神经病则伴随着周围神经的损伤。外周和中枢损伤后钠通道的表达可能存在差异，因为三叉神经痛患者通常对卡马西平有反应，而外周三叉神经病患者仅使用卡马西平很少能获得显著缓解。不同纤维类型的钠通道的不同表达也可能是外周和中枢损伤后疼痛的不同临床特征的原因。识别损伤后特定的钠通道改变可能有助于开发更具选择性的神经病理性疼痛治疗方法。