奶油
神经病理性疼痛
突触后密度
痛觉过敏
脊髓
NMDA受体
长时程增强
医学
痛觉超敏
神经科学
敏化
药理学
慢性疼痛
内科学
麻醉
化学
伤害
受体
生物
生物化学
转录因子
基因
作者
Fengqin Xu,Xin Zhao,Lin Liu,Jia Song,Yan Zhu,Shuaishuai Chu,Xueming Shao,Xiuxiu Li,Zhengliang Ma,Xiaoping Gu
出处
期刊:Neuroreport
[Ovid Technologies (Wolters Kluwer)]
日期:2017-09-06
卷期号:28 (13): 856-863
被引量:12
标识
DOI:10.1097/wnr.0000000000000849
摘要
Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.
科研通智能强力驱动
Strongly Powered by AbleSci AI