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Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia

Author

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  • Satoru Koyanagi

    (Faculty of Pharmaceutical Sciences, Kyushu University
    Faculty of Pharmaceutical Sciences, Kyushu University)

  • Naoki Kusunose

    (Faculty of Pharmaceutical Sciences, Kyushu University
    Present address: Department of Ophthalmology, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasamamachi Yufu-shi, Oita 879-5593, Japan)

  • Marie Taniguchi

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Takahiro Akamine

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Yuki Kanado

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Yui Ozono

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Takahiro Masuda

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Yuta Kohro

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Naoya Matsunaga

    (Faculty of Pharmaceutical Sciences, Kyushu University
    Faculty of Pharmaceutical Sciences, Kyushu University)

  • Makoto Tsuda

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Michael W. Salter

    (Program in Neuroscience and Mental Health, Hospital for Sick Children
    University of Toronto
    University of Toronto Centre for the Study of Pain)

  • Kazuhide Inoue

    (Faculty of Pharmaceutical Sciences, Kyushu University)

  • Shigehiro Ohdo

    (Faculty of Pharmaceutical Sciences, Kyushu University)

Abstract

Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn. We identify serum- and glucocorticoid-inducible kinase-1 (SGK-1) as the key molecule responsible for the glucocorticoid-enhanced release of ATP from astrocytes. SGK-1 protein levels in spinal astrocytes are increased in response to glucocorticoid stimuli and enhanced ATP release by opening the pannexin-1 hemichannels. Our findings reveal an unappreciated circadian machinery affecting pain hypersensitivity caused by peripheral nerve injury, thus opening up novel approaches to the management of chronic pain.

Suggested Citation

  • Satoru Koyanagi & Naoki Kusunose & Marie Taniguchi & Takahiro Akamine & Yuki Kanado & Yui Ozono & Takahiro Masuda & Yuta Kohro & Naoya Matsunaga & Makoto Tsuda & Michael W. Salter & Kazuhide Inoue & S, 2016. "Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13102
    DOI: 10.1038/ncomms13102
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