title: Protein kinases mediate increment of the phosphorylation of cyclic AMP-responsive element binding protein in spinal cord of rats following capsaicin injection.
abstract: BACKGROUND
  Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection.
  
  
  RESULTS
  We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group.
  
  
  CONCLUSIONS
  These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, TX 77030-1501, USA. jing.wu@uth.tmc.edu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Su
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Lei
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Fang
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010146:Pain; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002211:Capsaicin