EFFECTS OF DORSAL ROOT GANGLION NEURON AXOTOMY

背根神经节轴切术的影响

• 批准号: 3078162
• 负责人: KIM J BURCHIEL
• 金额: $ 5.62万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3078162
• 关键词: denervation; dorsal root; electrophysiology; electrostimulus; microelectrodes; nervous system regeneration; neural transmission; neuropharmacology; pain; peripheral nervous system; psychophysiology; spinal ganglion

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.

这项建议解决了中央和外围设备如何 神经系统会因损伤而改变，因此疼痛可以在 没有伤害性刺激。一种可能的机制，其中 可能是通过从基因座异位产生伤害性输入 外周损伤后的外周感受器近端 很有胆量。我建议通过量化来检验这一假设 外周和外周神经生理、形态和行为的影响 大鼠背根神经节(DRG)神经元的中枢神经切断。上一首 调查表明，在切断周围神经后， 相关的DRG开始产生异位活动，主要是在小的 有髓和无髓传入纤维。在一段时间里， 神经节神经元和动物体内发生了染色变化。 会在麻醉区表现出感觉障碍的恶果 (自动切割法)。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神经元的染色改变和自发放电是继发性的 神经轴突切断术的形态和生理表现 2)去神经后的自体切断术 继发源于伤害性传入的自发放电 背侧可延缓或阻止自体切断 根神经节切除术；4)电气、机械和药理学 刺激可调制背根神经节神经元的自发放电 神经损伤。这种制剂可以模拟特定的疼痛综合征， 出现在失神经后(即幻肢疼痛、麻醉疼痛)， 并提供了一个可访问的主要结构和功能模型 外周和中枢神经切断后背根神经节的变化。