CHANGES IN DORSAL HORN CIRCUITRY IN NEUROPATHIC PAIN

本项目的目的是测试假设， 诱导Abeta初级传入纤维出芽进入板层II 是神经性疼痛的基础 这个假设的检验是：1）将行为变化与 （机械性异常性疼痛、冷异常性疼痛、持续性疼痛） 变化（DRG细胞、DRG轴突和中枢突触的丢失， 板层II）中的Abeta纤维，和2）防止形态学变化， 表明疼痛行为并没有发展。 用于L5和L6脊柱横断的这些测试的系统 神经在大鼠（钟模型），这导致一致的 神经性疼痛 其理由是，外周感觉神经切断术会导致一些人死亡， DRG细胞，随后进行中枢去神经支配，并启动其他细胞。 这种中枢去神经支配和启动细胞的组合导致 中央纤维在失神经支配区域发芽。 我们尤其 已经发现，在神经损伤后，Abeta纤维发芽进入板层II。 我们假设大的感觉纤维的入口通常 关注的是轻触和精细的区分， 正常处理的伤害性输入在产生 某些类型的疼痛。 该项目的一个关键部分是阻止Abeta发芽进入第二层。 我们提出的方法是阻止DRG细胞的丢失。 我们 理由是，这将阻止中枢初级传入神经的损失， 如果是这样的话，脊髓中就不会有突触空缺， 因此没有地方让活性纤维发芽。 我们的两个程序 意见提供了最好的机会，以阻止神经后感觉细胞的损失 病变，神经生长因子（NGF）的中央残端管理 或将横切的神经残端放置在不可渗透的管中。

The present project is designed to test the hypothesis that post-axotomy induced sprouting of Abeta primary afferent fibers into lamina II underlies neuropathic pain. The tests of this hypothesis are 1) to correlate the behavioral changes (mechanical allodynia, cold allodynia, ongoing pain) with the morphologic changes (loss of DRG cells, DRG axons and central synapses, sprouting of Abeta fibers in lamina II), and 2) to prevent the morphologic changes and show that the pain behavior does not develop. The system used for these tests in transection of the L5 and L6 spinal nerves in the rat (the Chung model), which results in consistent neuropathic pain. The reasoning is that peripheral sensory axotomy results in death of some DRG cells, with subsequent central denervation, and priming of the others. This combination of central denervation and primed cells results in sprouting of central fibers into the denervated areas. In particular we have found that Abeta fibers sprout into lamina II after nerve lesions. We hypothesize that the entrance of large sensory fibers normally concerned with light touch and fine discrimination into a region that normally processes nociceptive input plays a role in the production of certain types of pain. A key part of this project is to stop the Abeta sprouting into lamina II. Our proposed way to do this is to stop the loss of DRG cells. Our reasoning is that this will stop loss of central primary afferent synapses, and if so, there would be no synaptic vacancies in the cord and thus no place for activated fibers to sprout. Two procedures in our opinion give best chance for stopping loss of sensory cells after nerve lesions, administration of nerve growth factor (NGF) to the central stumps or placement of the transected nerve stumps in an impermeable tube.