School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Mol Pain. 2009 Dec 12;5:71. doi: 10.1186/1744-8069-5-71.
The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.
中脑导水管周围灰质（PAG）是已知在疼痛传递和调制中起作用的结构。有害刺激增强 PAG 中的谷氨酸突触传递，并增强谷氨酸 NMDA 受体表达。然而，对于 NMDA 受体亚基在处理持续性炎症疼痛中的作用知之甚少。本研究旨在研究 PAG 中的 NR2A 和 NR2B 型 NMDA 受体及其对周围疼痛性炎症的调制作用。足底注射完全弗氏佐剂（CFA）引起的有害刺激导致 PAG 中 NR2B 型 NMDA 受体上调，而 NR2A 型 NMDA 受体没有改变。全细胞膜片钳记录显示，在炎症痛的慢性期，NMDA 受体介导的 mEPSC 在 PAG 突触中显著增加。PAG 局部输注 NR2B 拮抗剂 Ro 25-6981 显著延长了双侧热辐射热刺激大鼠的足底退缩潜伏期。金丝桃苷（Hyp）是从 P. ponticum L. 中分离出的一种黄酮类化合物，可显著逆转 PAG 中 NR2B 型 NMDA 受体的上调，并对持续性炎症刺激表现出镇痛活性。我们的研究结果提供了有力的证据，表明 PAG 中 NR2B 型 NMDA 受体的上调参与了对周围持续性炎症疼痛的调制。
