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 Citations (Scopus)

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
Pages (from-to)55-67
Number of pages13
JournalNovartis Foundation symposium
Volume261
Publication statusPublished - Dec 1 2004

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Hyperalgesia
Microglia
Chronic Pain
Adenosine Triphosphate
Purinergic P2 Receptors
Spinal Cord
p38 Mitogen-Activated Protein Kinases
Wounds and Injuries
Spinal Injuries
Spinal Nerves
Oligodeoxyribonucleotides
Neuralgia
Sensory Receptor Cells
Nervous System
Pharmacology
Pain

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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

Chronic pain and microglia : The role of ATP. / Inoue, Kazuhide; Tsuda, Makoto; Koizumi, Schuichi; Mantyh; Baron; Malmberg; Devor; Dray; Oh; Perl.

In: Novartis Foundation symposium, Vol. 261, 01.12.2004, p. 55-67.

Research output: Contribution to journalArticle

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, vol. 261, pp. 55-67.
Inoue K, Tsuda M, Koizumi S, Mantyh, Baron, Malmberg et al. Chronic pain and microglia: The role of ATP. Novartis Foundation symposium. 2004 Dec 1;261:55-67.
Inoue, Kazuhide ; Tsuda, Makoto ; Koizumi, Schuichi ; Mantyh ; Baron ; Malmberg ; Devor ; Dray ; Oh ; Perl. / Chronic pain and microglia : The role of ATP. In: Novartis Foundation symposium. 2004 ; Vol. 261. pp. 55-67.
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