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

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 gl...

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Autores principales: Koyanagi, Satoru, Kusunose, Naoki, Taniguchi, Marie, Akamine, Takahiro, Kanado, Yuki, Ozono, Yui, Masuda, Takahiro, Kohro, Yuta, Matsunaga, Naoya, Tsuda, Makoto, Salter, Michael W., Inoue, Kazuhide, Ohdo, Shigehiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067584/
https://www.ncbi.nlm.nih.gov/pubmed/27739425
http://dx.doi.org/10.1038/ncomms13102
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author Koyanagi, Satoru
Kusunose, Naoki
Taniguchi, Marie
Akamine, Takahiro
Kanado, Yuki
Ozono, Yui
Masuda, Takahiro
Kohro, Yuta
Matsunaga, Naoya
Tsuda, Makoto
Salter, Michael W.
Inoue, Kazuhide
Ohdo, Shigehiro
author_facet Koyanagi, Satoru
Kusunose, Naoki
Taniguchi, Marie
Akamine, Takahiro
Kanado, Yuki
Ozono, Yui
Masuda, Takahiro
Kohro, Yuta
Matsunaga, Naoya
Tsuda, Makoto
Salter, Michael W.
Inoue, Kazuhide
Ohdo, Shigehiro
author_sort Koyanagi, Satoru
collection PubMed
description 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.
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spelling pubmed-50675842016-10-24 Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia Koyanagi, Satoru Kusunose, Naoki Taniguchi, Marie Akamine, Takahiro Kanado, Yuki Ozono, Yui Masuda, Takahiro Kohro, Yuta Matsunaga, Naoya Tsuda, Makoto Salter, Michael W. Inoue, Kazuhide Ohdo, Shigehiro Nat Commun Article 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. Nature Publishing Group 2016-10-14 /pmc/articles/PMC5067584/ /pubmed/27739425 http://dx.doi.org/10.1038/ncomms13102 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Koyanagi, Satoru
Kusunose, Naoki
Taniguchi, Marie
Akamine, Takahiro
Kanado, Yuki
Ozono, Yui
Masuda, Takahiro
Kohro, Yuta
Matsunaga, Naoya
Tsuda, Makoto
Salter, Michael W.
Inoue, Kazuhide
Ohdo, Shigehiro
Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title_full Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title_fullStr Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title_full_unstemmed Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title_short Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
title_sort glucocorticoid regulation of atp release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067584/
https://www.ncbi.nlm.nih.gov/pubmed/27739425
http://dx.doi.org/10.1038/ncomms13102
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