title: A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain.
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.
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. hujing2@fmmu.edu.cn
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhang
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Xu
authors.forename: Shui-Bing
authors.initials: SB
authors.lastname: Liu
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Fu-Xing
authors.initials: FX
authors.lastname: Zhang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Sun
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005620:Freund's Adjuvant; D018698:Glutamic Acid / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000378:metabolism; D009924:Organ Culture Techniques; D010147:Pain Measurement / Q000379:methods; D010148:Intractable Pain / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000378:metabolism* / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D018698:Glutamic Acid; C021304:hyperoside; D005620:Freund's Adjuvant; D011794:Quercetin