Document Detail


Differential contribution of spinal mitogen-activated protein kinases to the phase of long-lasting allodynia evoked by intrathecal administration of ATP in rats.
MedLine Citation:
PMID:  18520049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several lines of evidence suggest that activation of spinal mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) and p38 MAPK, contributes to the induction and maintenance of chronic pain. We recently reported that an intrathecal (i.t.) administration of ATP evoked tactile allodynia, which lasted more than 1 week in rats. The long-lasting allodynia was induced by activation of spinal P2X 2/3-receptors, and the induction and early phase of maintenance, but not the late phase, was mediated, at least in part, by the activation of spinal glial cells. In this study, we examined the involvement of spinal ERK and p38 MAPK in each phase of i.t. ATP-evoked long-lasting allodynia. I.t. administration of ATP (100 nmol) markedly increased phosphorylated ERK, which peaked at 1-8 h before gradually decreasing to a level that was sustained until 7 d after administration. In contrast, only a slight increase in phosphorylated p38 MAPK was observed. Consistent with the increased phosphorylation of MAPKs, the ERK kinase MEK inhibitor, U0126 (3 nmol), attenuated the induction phase (co-administration with ATP) and early maintenance phase (1-d post-ATP administration) of the i.t. ATP-evoked allodynia, but not the late maintenance phase (7-d post-ATP administration), while the p38 MAPK inhibitor, SB203580 (10 microg), had little effect. These results suggest that the induction phase and early maintenance phase, but not the late maintenance phase of long-lasting allodynia is mediated by the activation of ERK, rather than by the activation of p38 MAPK, in the spinal cord. These findings are informative for elucidating the mechanisms underlying the pathogenesis of chronic pain.
Authors:
Takayuki Nakagawa; Kayo Wakamatsu; Sanae Maeda; Hisashi Shirakawa; Shuji Kaneko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  31     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-03     Completed Date:  2008-06-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1164-8     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. tnakaga@pharm.kyoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate* / administration & dosage
Animals
Blotting, Western
Butadienes / pharmacology
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism
Imidazoles / pharmacology
Injections, Spinal
Male
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Nitriles / pharmacology
Pain / chemically induced*,  enzymology*
Pain Measurement / drug effects
Phosphorylation
Pyridines / pharmacology
Rats
Rats, Sprague-Dawley
Spinal Cord / enzymology*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
0/Butadienes; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Nitriles; 0/Pyridines; 0/SB 203580; 0/U 0126; 56-65-5/Adenosine Triphosphate; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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