Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury
Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury
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DOI：
10.1073/pnas.97.19.10584
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发表时间：
2000-09-12
影响因子：
11.1
通讯作者：
Wilcox, GL
中科院分区：
文献类型：
--
作者：
Fairbanks, CA;Schreiber, KL;Wilcox, GL
N-甲基-D-天冬氨酸亚类（NMDAR）的谷氨酸受体拮抗剂或一氧化氮合酶（NOS）抑制剂阻止神经系统可塑性。炎症性和神经性疼痛依赖于可塑性，这为在慢性疼痛中使用NMDAR拮抗剂和NOS抑制剂提供了临床机会。胍丁胺（AG）是一种存在于脑和脊髓中的内源性神经调质，具有NMDAR拮抗剂和NOS抑制剂活性。我们在这里报告说，AG，外源性给药啮齿动物，减少伴随炎症的痛觉过敏，正常化的机械超敏反应（异常性疼痛/痛觉过敏）产生的化学或机械神经损伤，并减少自切样行为和损伤大小后兴奋性毒性脊髓损伤。AC在急性疼痛试验中不产生抗伤害作用的情况下产生这些作用。在啮齿动物腰骶脊髓中也检测到内源性AG，其浓度与先前在大脑中检测到的浓度相似。证据表明AG在持续性疼痛和神经元损伤的基础过程中具有独特的抗可塑性和神经保护作用。
Antagonists of glutamate receptors of the N-methyl-D-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AC produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.