title: Role of phosphorylation of ERK in induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal horn.
abstract: Previous works have shown that activation of extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential for long-term potentiation (LTP) in hippocampus. In the present study, the role of the ERK/CREB pathway in LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathologic pain, was investigated in adult rats. Western blotting analysis showed that the protein level of phosphorylated ERK (p-ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP induction, starting at 15 min and returning to control at 60 min after tetanic stimulation and that the protein level of p-CREB increased at 30 min, persisting for at least 3 hr after LTP induction. Double immunofluorescence staining showed that p-ERK and p-CREB were only located in neurons but not in glial cells in the spinal dorsal horn after LTP induction. More importantly, we found that spinal application of PD 98059 (100 microM), a selective MEK inhibitor, at 30 min before tetanic stimulation blocked LTP induction and prevented the increase in p-ERK and p-CREB in spinal dorsal horn. When applied 15 min after LTP induction, PD98059 reversed established LTP. The drug, however, did not affect the spinal LTP, when applied at 30 min after LTP. Our results suggested that activation of ERK/CREB pathway in spinal dorsal neurons is necessary for induction and maintenance of long-term potentiation of the C-fiber evoked field potentials.
authors.affiliation: Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xin
authors.forename: Qing-Juan
authors.initials: QJ
authors.lastname: Gong
authors.forename: Ji-Tian
authors.initials: JT
authors.lastname: Xu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zang
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Li
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D007839:Functional Laterality; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005419:Flavonoids; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one