Wei F, Wang G D, Kerchner G A, Kim S J, Xu H M, Chen Z F, Zhuo M
Washington University Pain Center and Departments of Anesthesiology, Anatomy & Neurobiology, and Psychiatry, Washington University School of Medicine, Campus Box 8054, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA.
Nat Neurosci. 2001 Feb;4(2):164-9. doi: 10.1038/83993.
N-methyl-D-aspartate (NMDA) receptors contribute to many brain functions. We studied the effect of forebrain-targeted overexpression of the NMDA receptor subunit NR2B on the response of mice to tissue injury and inflammation. Transgenic mice exhibited prominent NR2B expression and enhanced NMDA receptor-mediated synaptic responses in two pain-related forebrain areas, the anterior cingulate cortex and insular cortex, but not in the spinal cord. Although transgenic and wild type mice were indistinguishable in tests of acute pain, transgenic mice exhibited enhanced responsiveness to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant. Genetic modification of forebrain NMDA receptors can therefore influence pain perception, which suggests that forebrain-selective NMDA receptor antagonists, including NR2B-selective agents, may be useful analgesics for persistent pain.
N-甲基-D-天冬氨酸（NMDA）受体参与多种脑功能。我们研究了前脑靶向过表达NMDA受体亚基NR2B对小鼠组织损伤和炎症反应的影响。转基因小鼠在两个与疼痛相关的前脑区域，即前扣带回皮层和岛叶皮层中表现出显著的NR2B表达，并增强了NMDA受体介导的突触反应，但在脊髓中未出现这种情况。尽管转基因小鼠和野生型小鼠在急性疼痛测试中没有差异，但转基因小鼠对外周注射两种炎症刺激物，即福尔马林和完全弗氏佐剂，表现出增强的反应性。因此，前脑NMDA受体的基因修饰可以影响痛觉，这表明包括NR2B选择性药物在内的前脑选择性NMDA受体拮抗剂可能是治疗持续性疼痛的有效镇痛药。
