P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury

Tsuda Makoto, Yukari Shigemoto-Mogami, Schuichi Koizumi, Akito Mizokoshi, Shinichi Kohsaka, Michael W. Salter, Kazuhide Inoue

Research output: Contribution to journalArticle

1082 Citations (Scopus)

Abstract

Pain after nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia - pain hypersensitivity evoked by innocuous stimuli. Effective therapy for this pain is lacking, and the underlying mechanisms are poorly understood. Here we report that pharmacological blockade of spinal P2X4 receptors (P2X 4Rs), a subtype of ionotropic ATP receptors, reversed tactile allodynia caused by peripheral nerve injury without affecting acute pain behaviours in naive animals. After nerve injury, P2X4R expression increased strikingly in the ipsilateral spinal cord, and P2X4Rs were induced in hyperactive microglia but not in neurons or astrocytes. Intraspinal administration of P2X4R antisense oligodeoxynucleotide decreased the induction of P2X4Rs and suppressed tactile allodynia after nerve injury. Conversely, intraspinal administration of microglia in which P2X 4Rs had been induced and stimulated, produced tactile allodynia in naive rats. Taken together, our results demonstrate that activation of P2X 4Rs in hyperactive microglia is necessary for tactile allodynia after nerve injury and is sufficient to produce tactile allodynia in normal animals. Thus, blocking P2X4Rs in microglia might be a new therapeutic strategy for pain induced by nerve injury.

Original languageEnglish
Pages (from-to)778-783
Number of pages6
JournalNature
Volume424
Issue number6950
DOIs
Publication statusPublished - Sep 1 2003

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury'. Together they form a unique fingerprint.

  • Cite this

    Makoto, T., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M. W., & Inoue, K. (2003). P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature, 424(6950), 778-783. https://doi.org/10.1038/nature01786