EVALUATION OF AN EXPERIMENTAL MODEL OF NEUROPATHIC PAIN

许多人患有慢性神经性疼痛（例如，causalgia， 三叉神经痛），几乎没有缓解的希望。 这种悲观情绪 持续存在是因为人们对正在发生的变化知之甚少 在神经系统的发展和进展过程中， 神经性疼痛 大鼠神经损伤的实验模型， 导致神经性疼痛的发展， 1988. 该模型称为神经慢性收缩模型， 损伤（CCI），似乎是第一个允许评估的变化 以及将这些变化与 痛觉过敏、异常性疼痛和自发性疼痛的行为表现 （感觉迟钝）。 CCI提供了非常真实的可能性， 在神经系统的潜在发展的慢性神经病变 疼痛终于可以解释了。 本研究的目的是使用CCI来评估 在受伤的早期阶段，神经系统中。 在 第一个项目，来自初级传入神经的电生理记录， 脊髓丘脑束起源处的纤维和神经元将 帮助评估感觉神经元反应特性的变化 在神经性疼痛的发展过程中。 第二个项目是 评估CCI损伤与其伴随的 神经性疼痛和坐骨神经的完全横断。 这 该项目将使用Fos蛋白（核磷蛋白）的抗体 哺乳动物原癌基因c-fos的产物）来标记神经元。 坐骨神经损伤后表达Fos的脊髓。 的 目的是了解更多关于脊髓神经元的位置， 按下Fos和以评估两者之间的表达差异 神经损伤 第三个项目包括两项研究。 评价 脊髓内内源性阿片肽水平的增加 强啡肽与行为性痛觉过敏的发生相关 CCI将撰写第一份研究报告。 第二项研究将评估 与初级传入相关的两个不同因素的重要性 纤维对脊髓强啡肽水平的增加。 这个目标 这项研究是为了评估谷氨酸释放的重要性， 初级传入纤维和受损的C纤维对 CCI后强啡肽增加。 阐明在神经系统中发生的变化， 神经病理性疼痛的发展为寻找干预措施提供了希望。 一旦了解了这些变化，就有可能开始临床 测试能够逆转这些变化的干预措施的试验， 防止神经性疼痛的发展。 此外，本发明还 了解潜在的变化提供了机会， 可能显著改善患者预后的新疗法 已经患有神经性疼痛

Many people suffer from chronic neuropathic pain (e.g., causalgia, trigeminal neuralgia) with little hope for relief. This pessimism persists because there is little understanding of the changes occurring in the nervous system during the development and progression of neuropathic pain. An experimental model of nerve injury in the rat, which results in the development of neuropathic pain, was introduced in 1988. This model, referred to as the chronic constriction model of nerve injury (CCI), appears to be the first that allows evaluation of changes in the nervous system and the possibility of correlating these changes to the behavioral appearance of hyperalgesia, allodynia and spontaneous pain (dysesthesia). The CCI provides the very real possibility that changes in the nervous system underlying the development of chronic neuropathic pain finally may be amendable to elucidation. The goals of this research are to use the CCI to evaluate changes taking place in the nervous system during the early stages of the injury. In the first project, electrophysiological recordings from primary afferent fibers and from neurons at the origin of the spinothalamic tract will help evaluate alterations in the response properties of sensory neurons during the development of neuropathic pain. The second project will evaluate differences between the CCI injury, with its accompanying neuropathic pain, and a complete transection of the sciatic nerve. This project will use an antibody to Fos-protein (the nuclear phosphoprotein product of the mammalian proto-oncogene c-fos) to label neurons in the spinal cord that express Fos after an injury to the sciatic nerve. The goal is to understand more about the spinal location of neurons ex- pressing Fos and to evaluate differences in expression between the two nerve injuries. The third project Consists of two studies. Evaluation of increases in the spinal levels of the endogenous opioid peptide dynorphin correlated with development of behavioral hyperalgesia after the CCI will compose the first study. The second study will evaluate the importance of two different factors associated with primary afferent fibers on the increase in spinal levels of dynorphin. The goal of this study is to evaluate the importance of glutamate released from injured primary afferent fibers and the importance of injured C fibers on the increase in dynorphin seen after the CCI. Elucidating the changes occurring in the nervous system during development of neuropathic pain provide hope for finding interventions. Once the changes are understood, it will be possible to begin clinical trials testing interventions capable of reversing these changes and preventing the development of neuropathic pain. Additionally, understanding the underlying changes provide opportunity for producing new treatments that may significantly improve the prognosis of patients already suffering from neuropathic pain.