MECHANISMS OF CAUSALGIA

这项建议的长期目标是揭示 致残的神经性疾病，如灼痛症，以调查 在神经病理性疼痛的机制方面，建立了一种动物模型 单侧结扎大鼠L5和L6脊神经 导致可感知的神经病理性疼痛的各种行为体征 在人类交感神经维持性疼痛(SMP)患者中， 一种特殊类型的神经性疼痛，人们对此知之甚少。一系列 提出了一系列关于SMP机制的假说。 为了验证这些假设，我们提出了6个具体目标。1)测试是否 SMP严重依赖于伤者产生的异位放电 传入，神经病理性疼痛的行为测试将在 传导阻断受损传入神经的活动。2)测试 异位放电是否死于异常的发展 受损传入的肾上腺素能敏感性，单单位活动将 从损伤节段的背根丝和 全身应用肾上腺素能激动剂和拮抗剂的作用 要下定决心。3)检测异位放电是否是由于 交感神经节后纤维的萌发及其新生 感觉神经元、去甲肾上腺素能纤维和可能的突触 受伤的传入神经中的突触将用光和 抗体的电子显微镜免疫细胞化学标记 酪氨酸羟基酶。4)检验异位放电是否到期 对异常交感神经活动的发展，单一单位活动 将从支配神经节后交感神经纤维记录下来 脊神经结扎。5)测试是否诱发疼痛(痛觉过敏和 痛觉过敏)是由完整的(未受伤的) 传入，将进行神经病理性疼痛的行为测试 传导过程中阻断完整传入神经的活动。6)测试 当周围神经受损时，SMP是否更容易发育 近端损伤与远端损伤相比，远端损伤是由于 明显的肾上腺素能系统异常，肾上腺素能活动将 按照具体目标2-4中关于先前制定的两个目标的建议进行审查 由远端损伤产生的模型。 实现具体目标将导致更好地理解 以及一种改进的治疗神经病理性疼痛的方法。

The long term goal of this proposal is to uncover the mechanism of the disabling painful neuropathic disease, such as causalgia, TO investigate the mechanisms of neuropathic pain, an animal model is developed by ligating the L5 and L6 spinal nerves of the rat unilaterally, This results in various behavioral signs of neuropathic pain that can be sen in human patients with sympathetically maintained pain (SMP), a particular type of neuropathic pain that is poorly understood. A series of hypotheses concerning the mechanisms that underlie SMP is formulated. To test the hypotheses, 6 specific aims are proposed. 1) To test whether SMP critically depends on ectopic discharges arising from the injured afferents, behavioral tests for neuropathic pain will be performed during conduction block of the activity of injured afferents. 2) To test whether the ectopic discharge are die to the development of abnormal adrenergic sensitivity by injured afferents, single unit activity will be recorded from dorsal root filaments of the injured segments and the effects of systemically applied adrenergic agonists and antagonist will be determined. 3) To test whether the ectopic discharges are due to sprouting of sympathetic postganglionic fibers and their newly formed synapses on sensory neurons, the noradrenergic fiber and putative synapses in the injured afferents will be examined using light and electron microscopic immunocytochemical labeling for antibody against tyrosine hydroxylase. 4) T test whether the ectopic discharges are due to the development of abnormal sympathetic activity, single unit activity will be recorded form postganglionic sympathetic fibers innervating the ligated spinal nerves. 5) To test whether evoke d pain (allodynia and hyperalgesia) is produced by inputs carried by intact (uninjured) afferents, behavioural tests for neuropathic pain will be performed during conduction block of the activity of intact afferents. 6) To test whether SMP is much more readily developed when the peripheral nerve is injured proximally as compared to a distal injury due to a more pronounced abnormality of the adrenergic system, adrenergic activity will be examined as proposed in Specific Aims 2-4 on two previously developed models which are produced by a distal injury. Accomplishing the specific aims will result in a better understanding of and an improved treatment for disabling neuropathic pain.