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cAMP response-element binding protein participates in the phosphorylated extracellular signal-regulate kinase mediated neuropathic pain

SONG Xue-Song¹, XU Yan-Bing², CAO Jun-Li^2,*, HE Jian-Hua², ZHANG Li-Cai², ZENG Yin-Ming²

¹Department of Anesthesiology, First Clinical College of N. Bethune Centre Health Sciences, Jilin University, Changchun 130021, China；² Jiangsu Institute of Anesthesiology, Jiangsu Key Laboratory of Anesthesiology, Xuzhou 221002, China

Abstract

It has been reported that extracellular signal-regulate kinase (ERK) is involved in the modulation of nociceptive information and central sensitization produced by intense noxious stimuli and/or peripheral tissue inflammation. Few studies have explored the relationship between ERK and cAMP response-element binding protein (CREB) in neuropathic pain after nerve injury, such as chronic constriction injury (CCI) of the sciatic nerve. In the present study, CCI model was employed to investigate the activation of ERK on the expression of phosphorylated CREB (pCREB) in chronic neuropathic pain. Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica’s trifurcation at around 1.0- mm intervals with 4-0 silk suture. Mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered one day before and three consecutive days after CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and von Frey filaments respectively. The expression of pCREB and Fos were assessed by both Western blot and immunohistochemical analysis. The results showed that intrathecal injection of U0126 or ERK antisense ODN attenuated significantly CCI-induced mechanical and thermal hyperalgesia. Correlating with behavior results, the injection also markedly suppressed the increase of CCI-induced pCREB and c-Fos expression. The results obtained suggest that CREB participates in the pERK-mediated neuropathic pain.

Key words: cAMP response-element binding protein; neuropathic pain; c-fos; extracellular signal-regulate kinase

Received: 　　Accepted:

Corresponding author: 曹君利　　E-mail: caojl0310@163.com

Citing This Article：

SONG Xue-Song, XU Yan-Bing, CAO Jun-Li, HE Jian-Hua, ZHANG Li-Cai, ZENG Yin-Ming. cAMP response-element binding protein participates in the phosphorylated extracellular signal-regulate kinase mediated neuropathic pain. Acta Physiol Sin 2005; 57 (2): 139-146 (in Chinese with English abstract).