LESION INDUCED CHANGES IN SPINAL ARCHITECTURE & PAIN

顽固性疼痛是神经损伤后的一个主要公共卫生问题。人们对其潜在机制的理解还不够完善。然而，最近，在神经损伤后，通常与疼痛无关的大感觉纤维被显示发芽进入疼痛处理区域。这些大纤维使用谷氨酸作为递质，谷氨酸过度具有神经毒性。这导致了支持这一提议的基本公式，即这种新的输入导致谷氨酸从大型快速放电纤维涌入疼痛处理区，这种涌出是神经毒性的，被选择破坏的细胞主要是抑制性中间神经元，使疼痛处理区缺乏抑制性控制，防止这种破坏将改善神经损伤后的疼痛相关行为。这些具体的假设检验了这些想法。1.神经损伤导致主脊髓加工区部分神经元丢失。2.刺激大感觉神经纤维会大大增加这种损失。3.这种损失与活动有关。4.谷氨酸受体阻滞剂可减轻或消除这种损失。5.这种缺失对抑制性中间神经元具有选择性。6.神经刺激导致的细胞丢失具有行为后果。7.刺激诱导的细胞丢失本质上是一种细胞凋亡。如果这些假设得到证实，从临床的角度来看，关键因素是神经损伤后的神经纤维活动将导致脊髓中抑制性中间神经元的死亡。因此，阻止这种活动可能会改善抑制控制的丧失，从而具有治疗作用。

Intractable pains are a major public health problem following nerve lesions. The underlying mechanisms are imperfectly understood. Recently, however, large sensory fibers not normally concerned with pain are shown to sprout into pain processing regions following nerve lesions. These large fibers use glutamate as a transmitter, which is neurotoxic in excess. This leads to the basic formulation underlying this proposal, namely that this novel input leads to an outpouring of glutamate from large rapidly firing fibers into a pain processing region, that this outpouring is neurotoxic , that the cells selected for destruction are predominantly inhibitory interneurons, leaving a pain processing region devoid of inhibitory control, and that prevention of this destruction will ameliorate the pain related behaviors that follow nerve lesions. These specific hypotheses test these ideas. 1. That nerve lesions lead to some neuron loss in the main spinal processing region. 2. That stimulating large sensory fibers greatly increase this loss. 3. That this loss is activity dependent. 4. That the loss can be lessened or eliminated by glutamate receptor blockers. 5. That the loss is selective for inhibitory interneurons. 6. That the loss of cells caused by nerve stimulation has behavioral consequences. 7. The stimulation induced cell loss is largely apoptotic in nature. If these hypotheses are borne out, the key factor from a clinical point of view is that the nerve fiber activity that follows a nerve lesion would result in death of inhibitory interneurons in the spinal cord. Accordingly, preventing this activity might ameliorate the loss of inhibitory control and thus have therapeutic utility.