Activation of Extracellular Signal-Regulated Kinase in the Anterior Cingulate Cortex Contributes to the Induction and Expression of Affective Pain

被引:122
作者
Cao, Hong [1 ,2 ]
Gao, Yong-Jing [1 ,2 ,3 ]
Ren, Wen-Hua [1 ,2 ]
Li, Ting-Ting [1 ,2 ]
Duan, Kai-Zheng [1 ,2 ]
Cui, Yi-Hui [4 ]
Cao, Xiao-Hua [4 ]
Zhao, Zhi-Qi [1 ,2 ]
Ji, Ru-Rong [3 ]
Zhang, Yu-Qiu [1 ,2 ]
机构
[1] Fudan Univ, Inst Neurobiol, Inst Brain Sci, Shanghai 200032, Peoples R China
[2] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
[3] Harvard Univ, Dept Anesthesiol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA
[4] E China Normal Univ, Shanghai Inst Brain Funct Genom, Key Lab Brain Funct Genom, Minist Educ & Sci & Technol Commiss Shanghai Munc, Shanghai 200062, Peoples R China
基金
美国国家卫生研究院;
关键词
BINDING PROTEIN-PHOSPHORYLATION; DORSAL-HORN NEURONS; ERK MAP KINASE; QUINOLINIC ACID LESIONS; NOCICEPTIVE NEURONS; INFLAMMATORY PAIN; NMDA RECEPTOR; FORMALIN TEST; BEHAVIORAL SENSITIZATION; SYNAPTIC PLASTICITY;
D O I
10.1523/JNEUROSCI.4300-08.2009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:3307 / 3321
页数:15
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