Activation of extracellular signal-regulated kinase1/2 in the medial prefrontal cortex contributes to stress-induced hyperalgesia.

Abstract

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.

• Authors: Jian Qi, Chen Chen, Ya-Cheng Lu, Ting Zhang, Hao Xu, Yuan-Yuan Cui, Yan-Zhou Chen, Wen Wang, Yu-Lin Dong, Yun-Qing Li
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 50 Issue 3 Pg. 1013-23 (Dec 2014) ISSN: 1559-1182 [Electronic] United States
• PMID: 24799176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butadienes
• Enzyme Inhibitors
• Nitriles
• U 0126
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Butadienes (pharmacology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Hyperalgesia (etiology, metabolism)
• MAP Kinase Signaling System (drug effects, physiology)
• Nitriles (pharmacology)
• Phosphorylation (drug effects)
• Prefrontal Cortex (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Stress Disorders, Post-Traumatic (etiology, metabolism)
• Stress, Psychological (complications, metabolism)