Chronic pain and microglia: The role of ATP

Kazuhide Inoue, Makoto Tsuda, Schuichi Koizumi, Mantyh, Baron, Malmberg, Devor, Dray, Oh, Perl

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Pain following nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia. We have been studying the role of ATP receptors in pain, and have already reported that activation of the P2X2/3 heteromeric channel/receptor in primary sensory neurons causes acutely tactile allodynia. We report here that tactile allodynia under chronic pain states requires an activation of the P2X 4 ionotropic ATP receptor and p38 mitogen-activated protein kinase (MAPK) in spinal cord microglia. Two weeks after L5 spinal nerve injury, rats displayed a marked mechanical allodynia. In the rats, activated microglia were detected in the injury side of the dorsal horn where the level of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) was increased. We performed the doubleimmunostaining analysis using cell-type specific markers and found that phosphop38MAPK-positive cells were microglia. Moreover, intraspinal administration of p38MAPK inhibitor, SB203580, suppressed the allodynia. We also found that the expression level of P2X4 was increased strikingly in spinal cord microgila after nerve injury and that pharmacological blockade of P2X4 reversed the allodynia. Intraspinal administration of P2X 4 antisense oligodeoxynucleotide (ODN) reduced induction of P2X 4 and suppressed tactile allodynia. Taken together our results demonstrate that activation of P2X4 or p38 MAPK in spinal cord microglia is necessary for tactile allodynia following nerve injury.

Original languageEnglish (US)
Pages (from-to)55-67
Number of pages13
JournalNovartis Foundation Symposium
Volume261
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Medicine(all)

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    Inoue, K., Tsuda, M., Koizumi, S., Mantyh, Baron, Malmberg, Devor, Dray, Oh, & Perl (2004). Chronic pain and microglia: The role of ATP. Novartis Foundation Symposium, 261, 55-67.