LESION INDUCED CHANGES IN SPINAL ARCHITECTURE & PAIN

顽固性疼痛是神经损伤后的主要公共卫生问题。其潜在机制尚不完全清楚。然而，最近发现，在神经损伤后，与疼痛无关的大的感觉纤维在疼痛处理区萌发。这些大纤维使用谷氨酸作为递质，过量的谷氨酸是神经毒性的。这就引出了这一假说的基本表述，即这种新的输入导致谷氨酸从大的快速燃烧的纤维中流出到疼痛处理区域，这种流出是神经毒性的，被选择破坏的细胞主要是抑制性中间神经元，使疼痛处理区域缺乏抑制性控制，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. 神经损伤导致主要脊髓处理区域的一些神经元丢失。2. 刺激大的感觉纤维会大大增加这种损失。3. 这种损失依赖于活动。4. 谷氨酸受体阻滞剂可以减轻或消除这种损失。5. 这种丧失对抑制性中间神经元是选择性的。6. 神经刺激导致的细胞损失会对行为产生影响。7. 刺激诱导的细胞损失在本质上主要是凋亡。如果这些假设得到证实，从临床角度来看，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，预防这种活性可能会改善抑制控制的丧失，从而具有治疗效用。

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.