P2X receptors-mediated cytosolic phospholipase A2 activation in primary afferent sensory neurons contributes to neuropathic pain

Tsuda Makoto, Shigeo Hasegawa, Kazuhide Inoue

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Activation of P2X3 and P2X2/3 receptors (P2X 3R/P2X2/3R), 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 (cPLA2) as a downstream molecule that mediates the P2X3R/P2X2/3R-dependent neuropathic pain. We found that applying ATP to cultured dorsal root ganglion (DRG) neurons increased the level of Ser505-phosphorylated cPLA2 and caused translocation of Ser505-phosphorylated cPLA2 to the plasma membrane. The ATP-induced cPLA2 activation was inhibited by a selective antagonist of P2X 3R/P2X2/3R and by a selective inhibitor of cPLA 2. In the DRG in vivo, the number of cPLA2-activated neurons was strikingly increased after peripheral nerve injury but not after peripheral inflammation produced by complete Freund's adjuvant. Pharmacological blockade of P2X3R/P2X2/3R reversed the nerve injury-induced cPLA2 activation in DRG neurons. Moreover, administering the cPLA2 inhibitor near the DRG suppressed nerve injury-induced tactile allodynia, a hallmark of neuropathic pain. Our results suggest that P2X3R/P2X2/3R-dependent cPLA2 activity in primary sensory neurons is a key event in neuropathic pain and that cPLA2 might be a potential target for treating neuropathic pain.

Original languageEnglish
Pages (from-to)1408-1416
Number of pages9
JournalJournal of Neurochemistry
Volume103
Issue number4
DOIs
Publication statusPublished - Nov 1 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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