Pharmacologically inhibiting GluR2 internalization alleviates   neuropathic pain

doi:10.1007/s12264-015-1556-2

CORC > 北京大学 > 生命科学学院

	Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain
	Liu, Tao-Yan ; Cheng, Yong ; Qin, Xiao-Yan ; Yu, Long-Chuan
刊名	NEUROSCIENCE BULLETIN
	2015
关键词	periaqueductal grey AMPA receptor GluA(2-3y) internalization morphine hindpaw withdrawal latency AMPA RECEPTOR TRAFFICKING PERIAQUEDUCTAL GRAY GENERAL-POPULATION RATS MONONEUROPATHY SENSITIZATION PREVALENCE ACTIVATION NEURONS
DOI	10.1007/s12264-015-1556-2
英文摘要	Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments, so it is critical to find new drugs for this condition. Recently, the cellsurface trafficking of pain-related receptors has been suggested as an important mechanism underlying persistent neuropathic pain. Here, we used the short peptide GluA(2-3y), which specifically inhibits the GluA2-dependent endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and tested its anti-nociceptive effect in the periaqueductal grey (PAG) of intact rats and rats with neuropathic pain. Intra-PAG injection of 0.15, 1.5, 7.5, and 15 pmol of GluA(2-3y) induced dose-dependent increases in hindpaw withdrawal latencies to noxious thermal and mechanical stimuli in intact rats, suggesting that GluA2 cell-surface trafficking in the PAG is involved in pain modulation. Furthermore, GluA(2-3y) had much stronger anti-nociceptive effects in rats with neuropathic pain induced by sciatic nerve ligation. Interestingly, the intra-PAG injection of 15 pmol GluA(2-3y) had an analgesic effect similar to 10 mu g (35 nmol) morphine in rats with neuropathic pain. Taken together, our results suggested that GluA2 trafficking in the PAG plays a critical role in pain modulation, and inhibiting GluA2 endocytosis with GluA(2-3y) has potent analgesic effects in rats with neuropathic pain. These findings strongly support the recent hypothesis that targeting receptor trafficking could be a new strategy for the treatment of neuropathic pain.; supported by the National Natural Science Foundation of China,support from the Minzu University 985 Academic Team-building Fund,the 111 Project of China; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); ARTICLE; chengy4@mail.nih.gov; zhongsijia01@163.com; 5; 611-616; 31
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/451425]
专题	生命科学学院
推荐引用方式 GB/T 7714	Liu, Tao-Yan,Cheng, Yong,Qin, Xiao-Yan,et al. Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain[J]. NEUROSCIENCE BULLETIN,2015.
APA	Liu, Tao-Yan,Cheng, Yong,Qin, Xiao-Yan,&Yu, Long-Chuan.(2015).Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain.NEUROSCIENCE BULLETIN.
MLA	Liu, Tao-Yan,et al."Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain".NEUROSCIENCE BULLETIN (2015).