IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v424y2003i6950d10.1038_nature01786.html
   My bibliography  Save this article

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

Author

Listed:
  • Makoto Tsuda

    (National Institute of Health Sciences
    The Hospital for Sick Children)

  • Yukari Shigemoto-Mogami

    (National Institute of Health Sciences)

  • Schuichi Koizumi

    (National Institute of Health Sciences)

  • Akito Mizokoshi

    (Kyushu University)

  • Shinichi Kohsaka

    (National Institute of Neuroscience)

  • Michael W. Salter

    (The Hospital for Sick Children)

  • Kazuhide Inoue

    (National Institute of Health Sciences
    Kyushu University)

Abstract

Pain after nerve damage is an expression of pathological operation of the nervous system1,2, 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 (P2X4Rs)3,4,5,6,7, a subtype of ionotropic ATP receptor8, 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 P2X4Rs had been induced and stimulated, produced tactile allodynia in naive rats. Taken together, our results demonstrate that activation of P2X4Rs 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.

Suggested Citation

  • Makoto Tsuda & Yukari Shigemoto-Mogami & Schuichi Koizumi & Akito Mizokoshi & Shinichi Kohsaka & Michael W. Salter & Kazuhide Inoue, 2003. "P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury," Nature, Nature, vol. 424(6950), pages 778-783, August.
  • Handle: RePEc:nat:nature:v:424:y:2003:i:6950:d:10.1038_nature01786
    DOI: 10.1038/nature01786
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature01786
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature01786?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. N Ruiz-Suarez & SFM Bhatti & M Hermans & CB Silva & M Hesta, 2021. "Food hypersensitivity and feline hyperaesthesia syndrome (FHS): A case report," Veterinární medicína, Czech Academy of Agricultural Sciences, vol. 66(8), pages 363-367.
    2. Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Yiyi Ma & Eric B. Dammer & Daniel Felsky & Duc M. Duong & Hans-Ulrich Klein & Charles C. White & Maotian Zhou & Benjamin A. Logsdon & Cristin McCabe & Jishu Xu & Minghui Wang & Thomas S. Wingo & James, 2021. "Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. George Sideris-Lampretsas & Silvia Oggero & Lynda Zeboudj & Rita Silva & Archana Bajpai & Gopuraja Dharmalingam & David A. Collier & Marzia Malcangio, 2023. "Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Cheng Shen & Yuqing Zhang & Wenwen Cui & Yimeng Zhao & Danqi Sheng & Xinyu Teng & Miaoqing Shao & Muneyoshi Ichikawa & Jin Wang & Motoyuki Hattori, 2023. "Structural insights into the allosteric inhibition of P2X4 receptors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:424:y:2003:i:6950:d:10.1038_nature01786. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.