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- Title
P2X receptors-mediated cytosolic phospholipase A<sub>2</sub> activation in primary afferent sensory neurons contributes to neuropathic pain.
- Authors
Tsuda, Makoto; Hasegawa, Shigeo; Inoue, Kazuhide
- Abstract
Activation of P2X3 and P2X2/3 receptors (P2X3R/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 A2 (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 P2X3R/P2X2/3R and by a selective inhibitor of cPLA2. 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.
- Subjects
NEURONS; SENSORY neurons; CHRONIC pain; CHRONIC diseases; IMMUNOLOGICAL adjuvants; CELL membranes
- Publication
Journal of Neurochemistry, 2007, Vol 103, Issue 4, p1408
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.04861.x