Activation of Extracellular Signal-Regulated Kinase1/2 in the Medial Prefrontal Cortex Contributes to Stress-Induced Hyperalgesia
Activation of Extracellular Signal-Regulated Kinase1/2 in the Medial Prefrontal Cortex Contributes to Stress-Induced Hyperalgesia
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内侧前额皮质细胞外信号调节激酶 1/2 的激活导致压力诱发的痛觉过敏
DOI：
10.1007/s12035-014-8707-8
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发表时间：
2014-12-01
影响因子：
5.1
通讯作者：
Li, Yun-Qing
中科院分区：
文献类型：
--
作者：
Qi, Jian;Chen, Chen;Li, Yun-Qing
应激性刺激会加重持续性疼痛障碍。然而，其潜在的机制仍不清楚。为此，我们采用单次延长应激模型、完全弗氏佐剂模型和细胞外信号调节蛋白1/2调节蛋白1/2激活模型，研究了细胞外信号调节蛋白1/2(ERK1/2)的激活对慢性疼痛超敏反应的影响，以揭示应激性刺激诱导慢性痛觉过敏的可能机制。实验结果显示，与对照组相比，SPS、 + 和SPS CFA组小鼠的足爪缩足阈值显著降低。然而，与对照组相比，SPS或SPS + 染毒组大鼠内侧前额叶皮质ERK1/2的磷酸化水平增加，但未见明显的磷酸化。SPS + CFA治疗后mPFC ERK1/2的磷酸化和机械性痛觉过敏也显著高于SPS或CFA单独治疗。此外，通过向mPFC内微量注射MAPK抑制剂U0126来抑制ERK1/2的磷酸化，可减弱SP + 的CFA和SP，但不能减弱CFA诱导的机械痛觉异常、焦虑样行为和认知障碍。这些结果表明，mPFC中ERK1/2的激活可能参与了应激诱导的认知和情绪障碍的过程，从而导致疼痛敏感性的增加。
Stressful stimuli can exacerbate persistent pain disorder. However, the underlying mechanism is still unknown. Here, to reveal the underlying mechanism for stressful stimuli-induced hyperalgesia in chronic pain, we investigated the effect of extracellular signal-regulated kinase1/2 (ERK1/2) activation on pain hypersensitivity using single-prolonged stress (SPS) model, complete Freund’s adjuvant (CFA) model and SPS + CFA model. The experimental results revealed significantly reduced paw withdrawal threshold in the SPS, CFA, and SPS + CFA group compared with the control group. However, the increased phosphorylation of ERK1/2 in the medial prefrontal cortex (mPFC) was observed in the SPS- or SPS + CFA-exposed group but not the CFA group compared with control group. There was also a significant increase in mPFC ERK1/2 phosphorylation and mechanical allodynia after SPS + CFA treatment compared to SPS or CFA treatment alone. Furthermore, inhibiting ERK1/2 phosphorylation by microinjection of U0126, a MAPK kinase (MEK) inhibitor, into the mPFC attenuated SPS + CFA- and SPS- but not CFA-induced mechanical allodynia, anxiety-like behavior, and cognitive impairments. These results suggest that the activation of ERK1/2 in the mPFC may contribute to the process of stress-induced cognitive and emotional disorders, leading to an increase in pain sensitivity.