Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

Molecular Pain

Jian-ling Zuo¹  Xiu-yun Wang¹  Qi-nian Xu¹  Hao Cheng⁴  Fu-hai Ji⁴  Yan-bing Zhang⁴  Cai-fang Li⁴  Yan Peng⁴  Jun Peng³  Jian-ping Yang⁴  Ming Yao²  Li-na Wang⁴ 

[1] Brain research laboratory, The First Affiliated Hospital of Soochow University, Jiangsu 215006, China;Department of Anesthesiology, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China;The Library of the Second Military Medical University, ShangHai, 200433, China;Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

关键词: rat;    cAMP response element-binding protein (CREB);    extracellular signal-regulated protein kinase (ERK);    spinal cord;    hyperalgesia;    bone cancer pain;   

Others  :  865872
DOI  :  10.1186/1744-8069-7-48

 received in 2011-03-15, accepted in 2011-07-01,  发布年份 2011

【 摘 要 】

Background

Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed activation of spinal cells and the ERK/MAPK pathway in a rat model of bone cancer pain.

Results

A Sprague Dawley rat model of bone cancer pain was established and the model was evaluated by a series of tests. Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK inhibitor) was administered intrathecally. Western blots and double immunofluorescence were used to detect the expression and location of phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time between day 6 and day 18 is a reasonable period ("time window" as the remaining stages) to investigate bone cancer pain mechanisms and to research analgesic drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK) and the transcription factor cAMP response element-binding protein (p-CREB) increased in the spinal cord of CIBP rats, which was attenuated by intrathecal injection of fluorocitrate or U0126.

Conclusions

The ERK inhibitors could have a useful role in CIBP management, because the same target is expressed in various cells at different times.

【 授权许可】

   
2011 Wang et al; licensee BioMed Central Ltd.

【 图 表 】

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