Knock down of spinal NMDA receptors reduces NMDA and formalin evoked behaviors in rat
Knock down of spinal NMDA receptors reduces NMDA and formalin evoked behaviors in rat
复制标题
DOI：
10.1097/00001756-200001170-00010
复制
发表时间：
2000-01-17
期刊：
影响因子：
1.7
通讯作者：
Yang, J
中科院分区：
文献类型：
--
作者：
Garry, MG;Malik, S;Yang, J
慢性疼痛仍然是一个主要的健康问题，估计有70%的晚期癌症和炎症性疾病患者以及高达94%的脊髓损伤患者受到影响。虽然在慢性疼痛的药物治疗方面已经取得了进展，例如辅助药物的使用和更有效的给药方法，但临床疼痛管理的支柱仍然依赖于阿片类药物。在脊髓水平的NMDA受体激活已被证明在几种动物模型中的伤害感受（疼痛）的促进中起重要作用。不幸的是，有效的NMDA受体拮抗剂，如MK-801和APV，具有毒性和低安全性，这妨碍了它们的临床应用。我们目前的证据表明，使用反义寡核苷酸靶向NMDA-RI受体亚基（AS-NMDA-RI），但不是正义，废除NMDA和福尔马林诱导的行为。此外，我们表明，脊髓AS-NMDA-RI的管理结果在取消染色免疫反应NMDA-RI在脊髓。这些数据提供了新的证据，支持使用基因治疗方法在神经性疼痛的管理的可行性。NeuroReport 11：49-55（C）2000 Lippincott威廉姆斯和威尔金斯。
Chronic pain remains a major health problem afflicting an estimated 70% of patients with advanced cancer and inflammatory disorders, and up to 94% of patients with spinal cord injuries. Although progress has been made in the pharmacotherapy of chronic pain management, such as usage of adjuvant drugs and more effective methods of drug delivery, the mainstay of clinical pain management still depends on opiates. NMDA receptor activation, at the level of the spinal cord has been shown to play an important role in the facilitation of nociception (pain) in several animal models. Unfortunately, potent NMDA receptor antagonists, such as MK-801 and APV, have toxic properties and low safety margins that preclude their clinical use. We present evidence which indicates that the use of antisense oligonucleotides targeted to the NMDA-RI receptor subunit (AS-NMDA-RI), but not sense, abolishes NMDA and formalin induced behaviors. Moreover, we demonstrate that spinal administration of AS-NMDA-RI results in the abolition of staining for immunoreactive NMDA-RI in the spinal cord. These data provide novel evidence supporting the feasibility of the use of gene therapy approaches in the management of neuropathic pain. NeuroReport 11:49-55 (C) 2000 Lippincott Williams & Wilkins.