Key Laboratory of Pain Basic Research & Clinical Therapy, Department of Neurobiology and Institute of Neuroscience, Medical College of Soochow University, Suzhou, China.
Acta Pharmacol Sin. 2011 Feb;32(2):160-6. doi: 10.1038/aps.2010.190.
AbstractAim:To investigate the role of glutamate and N-methyl-D-aspartate (NMDA) receptors in central sensitization following peripheral inflammation in the arcuate nucleus (ARC) of the mediobasal hypothalamus.
Mediobasal hypothalamic slices were prepared from rats undergoing peripheral inflammation, which was induced by a unilateral injection of complete Freund's adjuvant (CFA) into hind paw. Neuronal activation levels in the ARC were monitored by recording extracellular unit discharges. The NMDA receptor NR1 subunit (NR1) was measured using Western blot analysis.
Enhanced NR1 phosphorylation was observed in the ARC of CFA-inflamed rats. Compared with the control rats, the firing rate of spontaneous discharges in ARC neurons of inflamed rats was significantly higher, and it was significantly reduced both by an NMDA receptor antagonist (MK-801, 300 μmol/L) and by a non-NMDA receptor antagonist (CNQX, 30 μmol/L). Application of exogenous glutamate (200 μmol/L) or NMDA (25 μmol/L) resulted in increased neuronal discharges for ARC neurons, which was enhanced to a greater extent in inflamed rats than in control rats.
Glutamate receptor activation in the hypothalamic ARC plays a crucial role in central sensitization associated with peripheral inflammation.
探讨谷氨酸和 N-甲基-D-天冬氨酸（NMDA）受体在中枢敏化中的作用，这种敏化是在外周炎症作用于下丘脑弓状核（ARC）时产生的。
通过在单侧后爪注射完全弗氏佐剂（CFA）来诱导外周炎症，制备出中脑基底部下丘脑切片。通过记录细胞外单位放电来监测 ARC 中的神经元激活水平。使用 Western blot 分析测量 NMDA 受体 NR1 亚基（NR1）。
在 CFA 致炎大鼠的 ARC 中观察到增强的 NR1 磷酸化。与对照大鼠相比，炎性大鼠 ARC 神经元的自发性放电率明显更高，NMDA 受体拮抗剂（MK-801，300 μmol/L）和非 NMDA 受体拮抗剂（CNQX，30 μmol/L）均可显著降低其放电率。外源性谷氨酸（200 μmol/L）或 NMDA（25 μmol/L）的应用导致 ARC 神经元的放电增加，而在炎性大鼠中比在对照大鼠中增加得更为明显。
下丘脑 ARC 中的谷氨酸受体激活在与外周炎症相关的中枢敏化中起关键作用。
