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Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

Author

Listed:
  • Ikuko Takeda

    (National Institute for Physiological Sciences
    Nagoya University
    National Institute for Physiological Sciences)

  • Kohei Yoshihara

    (Kyushu University)

  • Dennis L. Cheung

    (National Institute for Physiological Sciences)

  • Tomoko Kobayashi

    (National Institute for Physiological Sciences)

  • Masakazu Agetsuma

    (National Institute for Physiological Sciences
    Kyushu University)

  • Makoto Tsuda

    (Kyushu University)

  • Kei Eto

    (National Institute for Physiological Sciences
    Kitasato University)

  • Schuichi Koizumi

    (University of Yamanashi
    University of Yamanashi)

  • Hiroaki Wake

    (Nagoya University
    National Institute for Physiological Sciences
    Kobe University)

  • Andrew J. Moorhouse

    (The University of New South Wales)

  • Junichi Nabekura

    (National Institute for Physiological Sciences
    Nagoya University
    Graduate University for Advanced Studies, SOKENDAI)

Abstract

Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.

Suggested Citation

  • Ikuko Takeda & Kohei Yoshihara & Dennis L. Cheung & Tomoko Kobayashi & Masakazu Agetsuma & Makoto Tsuda & Kei Eto & Schuichi Koizumi & Hiroaki Wake & Andrew J. Moorhouse & Junichi Nabekura, 2022. "Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31773-8
    DOI: 10.1038/s41467-022-31773-8
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    References listed on IDEAS

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    1. Cynthia D. Rittenhouse & Harel Z. Shouval & Michael A. Paradiso & Mark F. Bear, 1999. "Monocular deprivation induces homosynaptic long-term depression in visual cortex," Nature, Nature, vol. 397(6717), pages 347-350, January.
    2. Won-Suk Chung & Laura E. Clarke & Gordon X. Wang & Benjamin K. Stafford & Alexander Sher & Chandrani Chakraborty & Julia Joung & Lynette C. Foo & Andrew Thompson & Chinfei Chen & Stephen J. Smith & Be, 2013. "Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways," Nature, Nature, vol. 504(7480), pages 394-400, December.
    3. Hiromu Monai & Masamichi Ohkura & Mika Tanaka & Yuki Oe & Ayumu Konno & Hirokazu Hirai & Katsuhiko Mikoshiba & Shigeyoshi Itohara & Junichi Nakai & Youichi Iwai & Hajime Hirase, 2016. "Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
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