MECHANISMS OF CAUSALGIA

本提案的长期目标是揭示 致残性疼痛性神经病，如头痛，以调查 神经病理性疼痛的机制，动物模型的开发， 单侧结扎大鼠L5和L 6脊神经， 导致神经性疼痛的各种行为体征， 在患有交感神经维持性疼痛（SMP）的人类患者中， 这是一种特殊类型的神经性疼痛，人们对此知之甚少。 一系列 的假设有关的机制，基础SMP制定。 为了验证假设，提出了6个具体目标。1)来测试是否 SMP严重依赖于损伤部位的异位放电 传入，神经性疼痛的行为测试将在 受损传入神经活动的传导阻滞。 2)测试 异位放电是否死于发展异常 肾上腺素敏感性受损传入，单个单位活动将 从受损节段的背根细丝和 全身应用的肾上腺素能激动剂和拮抗剂的作用将 被确定。3)为了测试异位放电是否是由于 交感神经节后纤维的出芽及其新生 突触的感觉神经元，去甲肾上腺素能纤维和假定的 将用光检查受损传入神经中的突触， 抗-IgG抗体的电镜免疫细胞化学标记 酪氨酸羟化酶4)T检验异位放电是否由于 交感神经活动异常的发展， 将记录从节后交感神经纤维支配的 脊髓神经结扎 5)为了测试是否引起疼痛（异常性疼痛和 痛觉过敏）是由完整（未受伤） 将进行神经性疼痛的传入、行为测试 在传导阻滞完整传入神经活动的过程中。6)测试 是否SMP更容易发展时，周围神经是 与远端损伤相比， 肾上腺素能系统的明显异常，肾上腺素能活动将 根据具体目标2-4的建议，对先前制定的两项 由远端损伤产生的模型。 实现这些具体目标将有助于更好地了解 以及用于致残性神经性疼痛的改进的治疗。

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.