CHANGES IN DORSAL HORN CIRCUITRY IN NEUROPATHIC PAIN

本项目旨在检验轴突切断术后 Aβ初级传入纤维向II板层的诱导发芽 是神经病理性疼痛的基础。 对这一假设的检验是1)将行为变化联系起来 (机械性疼痛、冷性疼痛、持续性疼痛) 变化(DRG细胞、DRG轴突和中央突触的丧失，发芽 Abeta纤维在椎板II)，以及2)防止形态变化和 表明疼痛行为不会发展。 在L5和L6脊柱横断中用于这些测试的系统 大鼠(Chung模型)的神经，这导致了一致的 神经性疼痛。 理由是外周感觉神经轴突切断术导致一些人死亡 DRG细胞，随后中枢去神经，并启动其他细胞。 这种中枢去神经和启动细胞的结合导致了 中央纤维发芽进入失神经区域。尤其是我们 已经发现，在神经损伤后，Abeta纤维发芽进入II层。 我们假设大感觉神经纤维的入口通常 关注轻微的触摸和细微的歧视，进入一个 正常加工的伤害性输入在产生伤害性信息时起作用 某些类型的疼痛。 这个项目的一个关键部分是阻止Abeta发芽进入II层。 我们提出的方法是阻止背根节细胞的丢失。我们的 推理是，这将阻止中央初级传入的丧失 突触，如果是这样的话，脊髓中就不会有突触空洞， 因此，活化的纤维没有发芽的地方。我们的两个过程 意见为阻止神经后感觉细胞丧失提供了最佳机会 损伤，向中央残端注射神经生长因子(NGF) 或将切断的神经残端放置在不透气的管子中。

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.