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前扣带回皮层细胞外信号调节激酶的激活有助于诱导和表达情感性疼痛 |
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Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain |
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Cao H., Gao Y.-J., Ren W.-H., Li T.-T., Duan K.-Z., Cui Y.-H., Cao X.-H., Zhao Z.-Q., Ji R.-R., Zhang Y.-Q. 2009/5/29 18:40:20 |
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Journal of Neuroscience, 2009, Volume 29, Issue 10
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The anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli. However, little is known about the molecular mechanisms involved. The present study demonstrated that extracellular signal-regulated kinase (ERK) activation in the ACC plays a crucial role in pain-related negative emotion. Intraplantar formalin injection produced a transient ERK activation in laminae V-VI and a persistent ERK activation in laminae II-III of the rostral ACC (rACC) bilaterally. Using formalin-induced conditioned place avoidance (F-CPA) in rats, which is believed to reflect the pain-related negative emotion, we found that blockade of ERK activation in the rACC with MEK inhibitors prevented the induction of F-CPA. Interestingly, this blockade did not affect formalin-induced two-phase spontaneous nociceptive responses and CPA acquisition induced by electric foot-shock or U69,593, an innocuous aversive agent. Upstream, NMDA receptor, adenylyl cyclase (AC) and phosphokinase A (PKA) activators activated ERK in rACC slices. Consistently, intra-rACC microinjection of AC or PKA inhibitors prevented F-CPA induction. Downstream, phosphorylation of cAMP response element binding protein (CREB) was induced in the rACC by formalin injection and by NMDA, AC and PKA activators in brain slices, which was suppressed by MEK inhibitors. Furthermore, ERK also contributed to the expression of pain-related negative emotion. Thus, when rats were re-exposed to the conditioning context for retrieval of pain experience, ERK and CREB were reactivated in the rACC, and inhibiting ERK activation blocked the expression of F-CPA. All together, our results demonstrate that ERK activation in the rACC is required for the induction and expression of pain-related negative affect. Copyright © 2009 Society for Neuroscience. |
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Correspondence Address: Ji, R.-R.; Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115; email: rrji@zeus.bwh.harvard.edu |
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疾病资源中心
摘自:《西氏内科学》,第23版
患者女性,21岁,因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解,但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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