NMDA Receptor Phosphorylation and Trafficking after Pain

疼痛后 NMDA 受体磷酸化和运输

• 批准号: 7099536
• 负责人: GARY JAY BRENNER
• 金额: $ 17.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7099536
• 关键词: C fiber; NMDA receptors; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; biological signal transduction; capsaicin; confocal scanning microscopy; dorsal horn; electrophysiology; heat stimulus; immunocytochemistry; immunoprecipitation; intracellular transport; laboratory rat; membrane transport proteins; mitogen activated protein kinase; neurons; pain; phosphorylation; protein kinase C; protein localization; protein structure function; synapses; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Central sensitization, an activity-dependent increase in the excitability of dorsal horn neurons generated by C-afferent input, is thought to be a primary mechanism responsible for the generation of pathological pain states. Enhanced activity of spinal cord dorsal horn N-methyl-D-aspartate (NMDA) receptors has been implicated in the development of central sensitization. The central hypothesis of this proposal is that peripheral nociceptive input can lead to central sensitization at least in part through altered phosphorylation and intracellular trafficking of dorsal horn NMDA receptors. The aim of this proposal is to examine changes in dorsal horn NMDA receptor subunit phosphorylation and subcellular distribution during the generation of central sensitization. In addition, intracellular signaling pathways involved in these noxious stimulus-induced NMDA receptor subunit changes will be investigated and correlated with pain behaviors. The proposed experiments will test several specific hypotheses: 1) Peripheral noxious stimulation sufficient to generate central sensitization alters NMDA receptor subunit phosphorylation in spinal cord dorsal horn neurons. 2) Peripheral noxious stimulation sufficient to generate central sensitization alters NMDA receptor subunit trafficking in spinal cord dorsal horn neurons. 3) Peripheral noxious stimulation induced changes in NMDA receptor subunit phosphorylation and trafficking are temporally related to behavioral measures of central sensitization. Although post-translational changes in the NMDA receptor are believed critical for the synaptic plasticity that underlies central sensitization, there has been little direct in vivo investigation of the hypothesis. Both phosphorylation and trafficking, from intracellular stores to the postsynaptic site, of NMDA receptors in dorsal horn neurons will be investigated as they relate to central pain hypersensitivity .

描述（由申请人提供）：中枢致敏，由c传入输入产生的背角神经元兴奋性的活动依赖性增加，被认为是产生病理性疼痛状态的主要机制。脊髓背角n -甲基- d -天冬氨酸（NMDA）受体活性的增强与中枢致敏的发展有关。该建议的中心假设是，外周伤害性输入至少部分通过改变背角NMDA受体的磷酸化和细胞内运输导致中枢致敏。

项目成果

Bradykinin and peripheral sensitization.

缓激肽和外周敏化。

• DOI: 10.1515/bc.2006.003
• 发表时间: 2006
• 期刊: Biological chemistry
• 影响因子: 3.7
• 作者: Wang,Haibin;Ehnert,Corina;Brenner,GaryJ;Woolf,CliffordJ
• 通讯作者: Woolf,CliffordJ