Trigeminal Neuropathic Pain Mechanisms

三叉神经病理性疼痛机制

• 批准号: 7130184
• 负责人: MICHAEL A HENRY
• 金额: $ 18.03万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7130184
• 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

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（由申请人提供）：慢性神经性疼痛可能是一种毁灭性的疾病，通常管理不足。最近疼痛研究的焦点是检查神经损伤后钠通道表达的变化，因为这些变化可能导致神经元过度兴奋和神经病理性疼痛的发展。本研究拟从光镜和电镜两个水平研究Nav1.1、Nav1.2、Nav1.3、Nav1.6、Nav1.7、Nav1.8和Nav1.9钠通道亚型在正常大鼠三叉神经初级传入纤维（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神经元中的分布。一旦确定了每种亚型的正常表达，则将在铬缝线损伤后的相同区域中评价该表达的变化; 1）眶下神经，或2）三叉神经根进入区，结合改变的伤害感受的行为测试。假设损伤后钠通道亚型的正常分布发生变化，这与伤害感受改变的行为证据相关，这些变化可能取决于损伤部位（外周vs.中枢），这些变化导致损伤后初级传入神经元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过度兴奋性。三叉神经系统是评价周围神经或中枢神经根损伤后钠通道表达差异的极好模型系统，因为在这些不同损伤后的人类中观察到不同的临床实体。三叉神经痛可能是由于神经根进入区损伤，而周围三叉神经病变则是由于周围神经损伤。周围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，而周围三叉神经病变患者很少仅用卡马西平获得显著缓解。钠通道在不同纤维类型中的差异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。损伤后特异性钠通道改变的鉴定可能有助于开发更有选择性的神经性疼痛治疗方法。