Source:http://linkedlifedata.com/resource/pubmed/id/17725579
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2007-10-26
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pubmed:abstractText |
Activation of P2X(3) and P2X(2/3) receptors (P2X(3)R/P2X(2/3)R), ionotropic ATP receptor subtypes, in primary sensory neurons is involved in neuropathic pain, a debilitating chronic pain that occurs after peripheral nerve injury. However, the underlying mechanisms remain unknown. We investigated the role of cytosolic phospholipase A(2) (cPLA(2)) as a downstream molecule that mediates the P2X(3)R/P2X(2/3)R-dependent neuropathic pain. We found that applying ATP to cultured dorsal root ganglion (DRG) neurons increased the level of Ser505-phosphorylated cPLA(2) and caused translocation of Ser505-phosphorylated cPLA(2) to the plasma membrane. The ATP-induced cPLA(2) activation was inhibited by a selective antagonist of P2X(3)R/P2X(2/3)R and by a selective inhibitor of cPLA(2). In the DRG in vivo, the number of cPLA(2)-activated neurons was strikingly increased after peripheral nerve injury but not after peripheral inflammation produced by complete Freund's adjuvant. Pharmacological blockade of P2X(3)R/P2X(2/3)R reversed the nerve injury-induced cPLA(2) activation in DRG neurons. Moreover, administering the cPLA(2) inhibitor near the DRG suppressed nerve injury-induced tactile allodynia, a hallmark of neuropathic pain. Our results suggest that P2X(3)R/P2X(2/3)R-dependent cPLA(2) activity in primary sensory neurons is a key event in neuropathic pain and that cPLA(2) might be a potential target for treating neuropathic pain.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, Cytosolic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2X2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2X3
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1471-4159
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1408-16
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17725579-Animals,
pubmed-meshheading:17725579-Enzyme Activation,
pubmed-meshheading:17725579-Enzyme Inhibitors,
pubmed-meshheading:17725579-Male,
pubmed-meshheading:17725579-Neurons, Afferent,
pubmed-meshheading:17725579-Pain,
pubmed-meshheading:17725579-Pain Measurement,
pubmed-meshheading:17725579-Phospholipases A2, Cytosolic,
pubmed-meshheading:17725579-Rats,
pubmed-meshheading:17725579-Rats, Wistar,
pubmed-meshheading:17725579-Receptors, Purinergic P2,
pubmed-meshheading:17725579-Receptors, Purinergic P2X2,
pubmed-meshheading:17725579-Receptors, Purinergic P2X3,
pubmed-meshheading:17725579-Spinal Nerves
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pubmed:year |
2007
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pubmed:articleTitle |
P2X receptors-mediated cytosolic phospholipase A2 activation in primary afferent sensory neurons contributes to neuropathic pain.
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pubmed:affiliation |
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi, Fukuoka, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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