title: Early intervention of ERK activation in the spinal cord can block initiation of peripheral nerve injury-induced neuropathic pain in 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 CCI-induced behavioral hypersensitivity had not developed yet. Moreover, the upregulation of pERK expression in ipsilateral spinal cord was associated with the increase in pCREB expression in bilateral spinal cord. Intrathecal administration of mitogen-activated protein kinase kinase (MEK) inhibitor U0126 before CCI can efficiently block and delay the CCI-induced mechanical allodynia and thermal hyperalgesia. These data suggest that activation of ERK and CREB in the spinal cord contributes to the initiation of peripheral nerve injury-induced pain hypersensitivity, and an early intervention strategy should be proposed.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Ru-Yi
authors.initials: RY
authors.lastname: Huang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Du
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D002070:Butadienes; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases