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The role of ERK in affective pain

ERK 在情感性疼痛中的作用

基本信息

批准号：
7169873
负责人：
RU-RONG JI
金额：
$ 3.03万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-12-15 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7169873
关键词：
Address Affect Affective Afferent Neurons Anger Animal Model Anterior Anxiety BDNF gene Brain-Derived Neurotrophic Factor CREB1 gene Calcium/calmodulin-dependent protein kinase Clinical Cognition Condition Coupled Cyclic AMP-Dependent Protein Kinases Development Emotional Emotions Esthesia Extracellular Signal Regulated Kinases FOS gene Family member Feeling Formalin Fright Gene Expression Generations Genes Genetic Transcription Glutamates Goals Grant Growth Factor Hyperalgesia Hypersensitivity In Situ Hybridization Injury Maintenance Mediating Memory Mitogen Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases N-Methyl-D-Aspartate Receptors Nature Nerve Fibers Neurons Numbers Pain Pathway interactions Peripheral Persistent pain Phosphorylation Play Posterior Horn Cells Proteins Regulation Role Secondary pain Sensory Signal Transduction Signaling Molecule Spinal Spinal cord posterior horn Stimulus Substance P Substance P Receptor Synaptic plasticity Testing Tissues Western Blotting allodynia cell type central sensitization cingulate cortex experience extracellular signal-regulated kinase 3 inflammatory neuropathic pain inflammatory pain insight long term memory mRNA Expression nerve injury painful neuropathy parent grant receptor response transcription factor

项目摘要

DESCRIPTION (provided by applicant) Painful stimuli evoke pain sensation as well as unpleasant emotional feelings, and the emotional responses should be considered as an essential part of the pain experience. Clinical observations indicate that the debilitating nature of persistent pain induced by tissue injury (inflammatory pain) and nerve injury (neuropathic pain) is related to the suffering or anxiety the pain induces. Both persistent pain induced hypersensitivity (including hyperalgesia: increased responsiveness to noxious stimuli, and allodynia: painful responses to innocuous stimuli) and accompanied negative emotion (such as anxiety, angry, worry, fear, aversion, and related memory) can be regulated by transcriptional, translational, and post-translational mechanisms. The MAP kinase family member ERK (extracellular signal-regulated kinase) plays an important role in intracellular signaling and is implicated in pain hypersensitivity via these regulatory mechanisms. In the parent grant (RO1 NS40698), we focus on the role of ERK activation in primary sensory and dorsal horn neurons associated with peripheral and central sensitization, inflammatory pain, and gene transcription. To extend our previous study, the aim of this Fogarty proposal is to assess the involvement of the ERK in persistent pain-induced negative emotion in the anterior cingulate cortex (ACC). The project will test the following hypotheses: 1) ERK is activated in the ACC neurons following pain-related emotional affect and persistent pain-induced hypersensitivity, 2) ERK activation leads to CREB phosphorylation and the expression of CRE-containing genes in the ACC, 3) ERK activation in the ACC contributes to the induction and maintenance of affective pain. A number of different approaches, including immunostaining, western blot, and in situ hybridization will be used to detect protein and mRNA expression. A formalin-induced conditioned place avoidance (F-CPA) animal model will be used to discriminate sensory and affective component of pain. These results should provide further insights into the role of an intracellular signal cascade in the generation of sensation and negative emotion of persistent pain.

描述（由申请人提供）疼痛刺激引起疼痛感觉以及不愉快的情绪感受，情绪反应应被视为疼痛体验的重要组成部分。临床观察表明，由组织损伤（炎性疼痛）和神经损伤（神经性疼痛）诱导的持续性疼痛的衰弱性质与疼痛诱导的痛苦或焦虑有关。持续性疼痛诱导的超敏反应（包括痛觉过敏：对有害刺激的反应性增加，和异常性疼痛：对无害刺激的疼痛反应）和伴随的负面情绪（如焦虑，愤怒，担心，恐惧，厌恶和相关记忆）都可以通过转录，翻译和翻译后机制进行调节。MAP激酶家族成员ERK（细胞外信号调节激酶）在细胞内信号传导中起重要作用，并通过这些调节机制参与疼痛超敏反应。在母基金（RO1 NS40698）中，我们专注于ERK激活在初级感觉和背角神经元中的作用，这些神经元与外周和中枢致敏、炎性疼痛和基因转录相关。为了扩展我们以前的研究，本Fogarty建议的目的是评估ERK参与前扣带皮层（ACC）持续性疼痛诱导的负面情绪。本研究将验证以下假设：1）在疼痛相关的情绪情感和持续性疼痛诱导的超敏反应后，ACC神经元中ERK被激活; 2）ERK激活导致ACC中CREB磷酸化和含CREB基因的表达; 3）ACC中ERK激活有助于情感性疼痛的诱导和维持。许多不同的方法，包括免疫染色，蛋白质印迹和原位杂交将用于检测蛋白质和mRNA的表达。福尔马林诱导的条件性位置回避（F-CPA）动物模型将用于区分疼痛的感觉和情感成分。这些结果应该提供进一步的见解的作用，细胞内的信号级联反应的产生的感觉和持续性疼痛的负面情绪。