Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia.
Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia.
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DOI：
10.1038/ncomms13102
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发表时间：
2016-10-14
影响因子：
16.6
通讯作者：
Ohdo, Shigehiro
中科院分区：
文献类型：
--
作者：
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
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. Neuropathic pain hypersensitivity is known to undergo diurnal variations, although the underlying mechanisms are not clear. Using a sciatic nerve-injury mouse model, the authors find such diurnal changes are mediated by glucocorticoid induced enhancement of ATP release from astrocytes via pannexin-1 hemichannels.
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影响因子：
5.3
作者：
Nakatsuka, T;Gu, JG
通讯作者：
Gu, JG
DOI：
10.1073/pnas.96.3.1059
发表时间：
1999-02-02
影响因子：
11.1
作者：
Dhabhar, FS;McEwen, BS
通讯作者：
McEwen, BS
影响因子：
9.2
作者：
Akhtar, RA;Reddy, AB;Kyriacou, CP
通讯作者：
Kyriacou, CP
影响因子：
4.8
作者：
Muehlbauer, Marcus;Chilton, Paula M.;Jobin, Christian
通讯作者：
Jobin, Christian
影响因子：
3.5
作者：
Koizumi, Schuichi;Fujishita, Kayoko;Inoue, Kazuhide
通讯作者：
Inoue, Kazuhide