Early intervention of ERK activation in the spinal cord can block initiation of peripheral nerve injury-induced neuropathic pain in rats

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Author:
HAN Mei(Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China)
HUANG Ru-Yi(Department of Life Science, Fudan University, Shanghai 200433, China)
DU Yi-Min(Department of Life Science, Fudan University, Shanghai 200433, China)
ZHAO Zhi-Qi(Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China)
ZHANG Yu-Qiu(Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 63, Issue 02, 2011
DOI:
Key Word:
allodynia;hyperalgesia;ERK-CREB signaling pathway;early intervention;spinal cord;rats

Abstract: The present study is to investigate whether the extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) signaling pathway contributes to the initiation of chronic constriction injury (CCI)-induced neuropathic pain in rats. Mechanical allodynia was assessed by measuring the hindpaw withdrawal threshold in response to a calibrated series of von Frey hairs. Thermal hyperalgesia was assessed by measuring the latency of paw withdrawal in response to a radiant heat source. The expressions of phosphor-ERK (pERK) and phosphor-CREB (pCREB) were examined using Western blot analysis and immunohistochemistry. An early robust increase in the expression of pERK on the spinal cords ipsilateral to injury was observed on day 1 after CCI, when the CCl-induced behavioral hypersensitivity had not developed yet. Moreover, the upregulation of pERK expression in ip-silateral spinal cord was associated with the increase in pCREB expression in bilateral spinal cord. Intrathecal administration of mito-gen-activated protein kinase kinase (MEK) inhibitor U0126 before CCI can efficiently block and delay the CCl-induced mechanical allodynia and thermal hyperalgesia. These data suggest that activation of ERK and CREB in the spinal cord contributes to the initia-tion of peripheral nerve injury-induced pain hypersensitivity, and an early intervention strategy should be proposed.

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