Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-26
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1408-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
P2X receptors-mediated cytosolic phospholipase A2 activation in primary afferent sensory neurons contributes to neuropathic pain.
pubmed:affiliation
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi, Fukuoka, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't