Chronic Compression of the Trigeminal Ganglia

描述（由申请人提供）：三叉神经痛（抽搐性douloureux）是一种异常疼痛的颅面疾病，其特征是面部强烈的刺痛，可能由轻触引起。在大多数情况下，疼痛可以追溯到血管对三叉神经根的慢性压迫，导致被压迫根的脱髓鞘。这些压迫和髓鞘形成的变化可能改变沿着神经根的Na+通道密度，可能导致异位放电和异常的纤维-纤维冲动传递。虽然一些Na+通道阻断抗癫痫药物在短期内是有帮助的，但许多患者最终接受了侵入性神经外科手术来修复神经根。然而，即使是手术，通常也只能提供暂时的缓解。限制新的、更有效的治疗方法发展的主要问题是缺乏准确模拟三叉神经痛的动物模型。RFA-DE-07-006“三叉神经系统相关疼痛的新模型”的两个主要目标之一是“促进慢性口面疼痛病症的新型动物模型的开发和利用。作为这两个目标的辅助，该倡议还鼓励开发新的患者和动物疼痛测量方法，这些方法是非侵入性的和客观的，并允许对疼痛进行行为或功能评估。“拟议研究的目标与这一目标密切相关，因为我们计划开发一种准确的、可预测的三叉神经痛动物模型。我们的初步工作表明，在三叉神经根附近经颅放置生物相容性超吸收聚合物，将根推到骨上，提供了一种非炎症慢性压迫的方法，模拟人类病理学。该技术是相对非侵入性和简单的执行。此外，这些实验表明，这些动物表现出与三叉神经痛的症状和体征高度一致的行为和电生理变化。我们建议进一步描述该模型，提供明确的终点来测试潜在的治疗方法，并检查三叉神经痛的机制。这些机制的研究，反过来，可以导致确定新的药物开发目标，以及基因治疗方法。

DESCRIPTION (provided by applicant): Trigeminal neuralgia (tic douloureux) is a devistatingly painful craniofacial disease, characterized by intense stabbing pains of the face which may be elicited by light touch. In the majority of cases, the pain can be traced to chronic compression of the trigeminal nerve roots by a blood vessel, leading to demyelination of the compressed roots. These compression and myelination changes may then alter Na+ channel density along the nerve root, possibly leading to ectopic discharges, and abnormal fiber-to-fiber transmission of impulses. Although some Na+ channel blocking anti-seizure drugs are helpful in the short-term, many patients end up having invasive neurosurgery to decompress the nerve root. Even surgery however, typically only provides temporary relief. A primary issue limiting the development of new, more effective therapies, has been the lack of an animal model which accurately simulates trigeminal neuralgia. One of the two main goals of RFA-DE-07-006 "New Models of Pain Relevant to the Trigeminal System" is to "stimulate the development and utilization of novel animal models of chronic orofacial pain conditions. As an adjunct to these two goals, this Initiative also encourages the development of novel measures of pain in patients and animals that are non-invasive and objective and that permit a behavioral or functional assessment of pain." The goal of the proposed research fits closely with this goal, in that we plan to develop an accurate, predictive animal model of trigeminal neuralgia. Our preliminary work has shown that transcranial placement of a biocompatible superabsorbant polymer next to the trigeminal nerve root pushes the root against the bone, providing a means of non-inflammatory chronic compression, simulating human pathology. The technique is relatively non-invasive and simple to perform. Furthermore, these experiments have shown that these animals demonstrate behavioral and electrophysiological changes that are highly consistent with the symptoms and signs of trigeminal neuralgia. We propose to further characterize this model, providing clear endpoints to test potential therapies and a means to examine mechanisms underlying trigeminal neuralgia. These mechanistic studies, in turn, can lead to the determination of new targets for pharmacdceutical development, as well as for gene therapy approaches.