EFFECTS OF DORSAL ROOT GANGLION NEURON AXOTOMY

这一建议涉及的问题是， 神经系统因损伤而改变，因此可以在 没有伤害性刺激。 一种可能的机制， 可能发生的情况是通过位点异位产生伤害性输入 在外周受体损伤后， 神经。 我建议通过定量研究这一假设， 神经生理学、形态学和行为学的影响， 中枢神经切断对大鼠背根神经节（DRG）神经元的影响。 先前 研究表明在切断外周神经之后， 相关的DRG开始产生异位活动，主要是在小 有髓和无髓传入神经。 几天后， 在神经节神经元内发生染色质溶解变化， 会在麻醉区域表现出感觉迟钝的症状 （autotomy）。 微丝记录技术，组织学和行为学 分析将用于检验以下假设：1） DRG神经元的溶色素改变和自发放电是继发性的 轴突切断，是形态和生理表现， 外周再生; 2）去神经后的自切术， 继发于自发放电的伤害性传入起源于 背根神经节可延迟或阻止自体切断 根神经节切除术; 4）电、机械和药物 刺激可以调节DRG神经元的自发放电， 神经损伤 这种制剂可以模拟特定的疼痛综合征， 在去神经支配后出现（即，幻肢痛、痛性麻醉）， 并提供了一个可访问的模型的主要结构和功能 外周和中枢轴突切断后DRG发生的变化。

This proposal addresses the question of how the central and peripheral nervous system is altered by injury such that pain can be experienced in the absence of nociceptive stimulation. A possible mechanism where this might occur is by ectopic generation of nociceptive input from loci proximal to the peripheral receptor subsequent to injury of the peripheral nerve. I propose to examine this hypothesis by quantitating the neurophysiological, morphological, and behavioral effects of peripheral and central axotomy on rat dorsal root ganglia (DRG) neurons. Previous investigations indicate that following severance of a peripheral nerve, associated DRG begin producing ectopic activity primarily in small myelinated and unmyelinated afferents. Over a period of days, chromatolytic changes develop within the ganglia neurons and the animal will exhibit evildence of dysesthesias in the anesthetic region (autotomy). Microfilament recording techniques, histologic and behavioral analyses will be used to examine the following hypotheses: 1) chromatolytic changes and spontaneous firing in DRG neurons are secondary to axotomy and are the morphologic and physiologic manifestations of peripheral regeneration, respectively; 2) autotomy following denervation is secondary to spontaneous firing in nociceptive afferents originating in part from DRG neurons; 3) autotomy can be delayed or prevented by dorsal root ganglionectomy; 4) electrical, mechanical and pharmacological stimulation can modulate spontaneous firing from DRG neurons following nerve lesion. This preparation may model specific pain syndromes which arise following denervation (i.e., phantom limb pain, anesthesia dolorosa), and offers an accessible model of the primary structural and functional changes which occur in DRG following peripheral and central axotomy.