Enhanced NMDA receptor NR1 phosphorylation and neuronal activity in the arcuate nucleus of hypothalamus following peripheral inflammation  

作　　者：Jian-ming PENG Long-sheng XU Qi ZHU Shan GONG Xian-min YU Shi-yu GUO Gen-cheng WU Jin TAO Xing-hong JIANG 

机构地区：[1]Key Laboratory of Pain Basic Research & Clinical Therapy, Department of Neurobiology and Institute of Neuroscience, Medical College of Soochow University, Suzhou 215123, China [2]Department of Biomedical Sciences, College of Medicine, Florida State University, Florida 32306, USA [3]State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

出　　处：《Acta Pharmacologica Sinica》2011年第2期160-166,共7页中国药理学报（英文版）

摘　　要：Aim： To investigate the role of glutamate and N-methyI-D-aspartate （NMDA） receptors in central sensitization following peripheral inflammation in the arcuate nucleus （ARC） of the mediobasal hypothalamus. Methods： 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. Results： 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 pmol/L） and by a non-NMDA receptor antagonist （CNQX, 30 pmol/L）. Application of exogenous glutamate （200 pmol/L） or NMDA （25 pmol/L） resulted in increased neuronal discharges for ARC neurons, which was enhanced to a greater extent in inflamed rats than in control rats. Conclusion： Glutamate receptor activation in the hypothalamic ARC plays a crucial role in central sensitization associated with peripheral inflammation.Aim： To investigate the role of glutamate and N-methyI-D-aspartate （NMDA） receptors in central sensitization following peripheral inflammation in the arcuate nucleus （ARC） of the mediobasal hypothalamus. Methods： 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. Results： 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 pmol/L） and by a non-NMDA receptor antagonist （CNQX, 30 pmol/L）. Application of exogenous glutamate （200 pmol/L） or NMDA （25 pmol/L） resulted in increased neuronal discharges for ARC neurons, which was enhanced to a greater extent in inflamed rats than in control rats. Conclusion： Glutamate receptor activation in the hypothalamic ARC plays a crucial role in central sensitization associated with peripheral inflammation.

关 键 词：arcuate nucleus （ARC） NMDA receptor NR1 phosphorylation INFLAMMATION central sensitization MK-801 CNQX 

分 类 号：R[医药卫生]