A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

doi:10.1186/1744-8069-5-71

Molecular Pain

Volume 5

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Liu SB
Guo HJ
Yang Q
Zhang FX
Sun XL
Zhao MG

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A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

Jing Hu¹^* , Zhe Wang²^* , Yan-Yan Guo¹^* , Xiao-Nan Zhang¹ , Zhao-Hui Xu¹ , Shui-Bing Liu¹ , Hong-Ju Guo¹ , Qi Yang¹ , Fu-Xing Zhang³ , Xiao-Li Sun¹ and Ming-Gao Zhao¹

¹School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China

²Department of Orthopaedics & Traumatology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China

³Department of Anatomy, School of Basic Medical Science, Fourth Military Medical University, Xi'an 710032, China

author email corresponding author email* Contributed equally

Molecular Pain 2009, 5:71doi:10.1186/1744-8069-5-71


Published:	12 December 2009

Abstract

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.