Differential roles of ERK, JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: Multi-electrode array recordings
Differential roles of ERK, JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: Multi-electrode array recordings
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ERK、JNK 和 p38 MAPK 在大鼠海马结构中疼痛相关的突触反应时空增强中的不同作用：多电极阵列记录
DOI：
10.1016/j.brainres.2011.01.076
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发表时间：
2011-03-25
期刊：
影响因子：
2.9
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Liu, Ming-Gang;Wang, Rui-Rui;Chen, Jun
众所周知，慢性疼痛会影响各种高级大脑功能，包括感知、情感、认知和记忆。然而，很少有研究对海马形成（HF）中疼痛引起的突触可塑性变化进行研究，海马形成（HF）是一个重要的区域，服务于疼痛的情感动机成分。本研究利用新开发的MED64多通道记录系统，揭示了外周持续性伤害感受对大鼠HF突触连接、传递和功能在时间和空间上的强烈影响。然而，这种与疼痛相关的空间和时间可塑性的潜在信号机制仍然不太清楚。作为一项初步研究，本研究试图研究丝裂原活化蛋白激酶（MAPK）成员在介导这种可塑性现象中的潜在不同作用。利用三种著名的MAPK抑制剂分别靶向细胞外信号调节激酶（ERK）、p38 MAPK和c-Jun n -末端激酶（JNK），结合成熟的MED64多位点记录系统，我们发现ERK和JNK介导的信号通路在长期增强（LTP）平台期的药理抑制作用，显著降低疼痛增强的LTP维持，而类似阻断p38 MAPK通路则显著进一步增强LTP维持。对于疼痛的空间放大，ERK和p38 MAPK似乎发挥相反的作用，前者积极参与，后者负向参与，而INK信号通路没有任何可检测到的作用。综上所述，这些结果表明MAPK家族的特定成员在调节HF中疼痛相关的空间和时间可塑性方面的不同作用是良好的
It is known that chronic pain affects various higher brain functions including perception, emotion, cognition, and memory. However, few studies have been performed to examine pain-induced synaptic plastic changes in the hippocampal formation (HF), an important region subserving affective-motivational component of pain. Our previous study has revealed a strong impact of peripheral persistent nociception on synaptic connection, transmission and function in the HF of rats, in both temporal and spatial domains, by using a newly developed MED64 multichannel recording system. However, the underlying signaling mechanisms for this pain-related spatial and temporal plasticity are still less understood. As an initial investigation, the present study attempted to examine potential different roles of the mitogen-activated protein kinase (MAPK) members in mediating this plastic phenomenon. By virtue of the three well-known MAPK inhibitors targeting extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK), respectively, in combination with the well-established MED64 multisite recording system, we found that pharmacological inhibition of the ERK- and JNK-mediated signaling pathway, at the plateau phase of the long-term potentiation (LTP), significantly decreased pain-enhanced LTP maintenance whereas similar blockade of p38 MAPK pathway dramatically further increased the potentiation. Regarding the spatial magnification of pain, ERK and p38 MAPK seemed to play opposing roles, with the former positively involved and the latter negatively involved, without any detectable effect of the INK signaling pathway. Together, these results suggest differential roles of the specific members of the MAPK family in mediating pain-associated spatial and temporal plasticity in the HF, which are in good