title: Region- or state-related differences in expression and activation of extracellular signal-regulated kinases (ERKs) in naïve and pain-experiencing rats.
abstract: BACKGROUND
  Extracellular signal-regulated kinase (ERK), one member of the mitogen-activated protein kinase (MAPK) family, has been suggested to regulate a diverse array of cellular functions, including cell growth, differentiation, survival, as well as neuronal plasticity. Recent evidence indicates a role for ERKs in nociceptive processing in both dorsal root ganglion and spinal cord. However, little literature has been reported to examine the differential distribution and activation of ERK isoforms, ERK1 and ERK2, at different levels of pain-related pathways under both normal and pain states. In the present study, quantitative blot immunolabeling technique was used to determine the spatial and temporal expression of ERK1 and ERK2, as well as their activated forms, in the spinal cord, primary somatosensory cortex (SI area of cortex), and hippocampus under normal, transient pain and persistent pain states.
  
  
  RESULTS
  In naïve rats, we detected regional differences in total expression of ERK1 and ERK2 across different areas. In the spinal cord, ERK1 was expressed more abundantly than ERK2, while in the SI area of cortex and hippocampus, there was a larger amount of ERK2 than ERK1. Moreover, phosphorylated ERK2 (pERK2), not phosphorylated ERK1 (pERK1), was normally expressed with a high level in the SI area and hippocampus, but both pERK1 and pERK2 were barely detectable in normal spinal cord. Intraplantar saline or bee venom injection, mimicking transient or persistent pain respectively, can equally initiate an intense and long-lasting activation of ERKs in all three areas examined. However, isoform-dependent differences existed among these areas, that is, pERK2 exhibited stronger response than pERK1 in the spinal cord, whereas ERK1 was more remarkably activated than ERK2 in the S1 area and hippocampus.
  
  
  CONCLUSIONS
  Taken these results together, we conclude that: (1) under normal state, while ERK immunoreactivity is broadly distributed in the rat central nervous system in general, the relative abundance of ERK1 and ERK2 differs greatly among specific regions; (2) under pain state, either ERK1 or ERK2 can be effectively phosphorylated with a long-term duration by both transient and persistent pain, but their response patterns differ from each other across distinct regions; (3) The long-lasting ERKs activation induced by bee venom injection is highly correlated with our previous behavioral, electrophysiological, morphological and pharmacological observations, lending further support to the functional importance of ERKs-mediated signaling pathways in the processing of negative consequences of pain associated with sensory, emotional and cognitive dimensions.
authors.affiliation: Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, PR China. anyangy@ccmu.edu.cn
authors.forename: She-Wei
authors.initials: SW
authors.lastname: Guo
authors.forename: Ming-Gang
authors.initials: MG
authors.lastname: Liu
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Long
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Ren
authors.forename: Zhuo-Min
authors.initials: ZM
authors.lastname: Lu
authors.forename: Hou-You
authors.initials: HY
authors.lastname: Yu
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Hou
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Cui-Ying
authors.initials: CY
authors.lastname: Gao
authors.forename: Xiu-Yu
authors.initials: XY
authors.lastname: Cui
authors.forename: Yang-Yuan
authors.initials: YY
authors.lastname: An
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001514:Bee Venoms; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001514:Bee Venoms; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3