Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats
Summary: Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223018692 |
| _version_ | 1797647812714823680 |
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| author | Hui Zhang Ang Li Yu-Fan Liu Zhong-Ming Sun Bing-Xin Jin Jia-Piao Lin Yan Yang Yong-Xing Yao |
| author_facet | Hui Zhang Ang Li Yu-Fan Liu Zhong-Ming Sun Bing-Xin Jin Jia-Piao Lin Yan Yang Yong-Xing Yao |
| author_sort | Hui Zhang |
| collection | DOAJ |
| description | Summary: Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain. |
| first_indexed | 2024-03-11T15:23:02Z |
| format | Article |
| id | doaj.art-42c2b5e49c6a41b181fe360970de2c94 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:23:02Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-42c2b5e49c6a41b181fe360970de2c942023-10-28T05:08:28ZengElsevieriScience2589-00422023-10-012610107792Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in ratsHui Zhang0Ang Li1Yu-Fan Liu2Zhong-Ming Sun3Bing-Xin Jin4Jia-Piao Lin5Yan Yang6Yong-Xing Yao7Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China; Department of Anesthesia, People’s Hospital of Guizhou Province, Guiyang, Guizhou 550025, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Neurobiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China; Centre for Neuroscience, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Corresponding authorDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China; Corresponding authorSummary: Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.http://www.sciencedirect.com/science/article/pii/S2589004223018692Molecular biologyNeuroscienceCell biology |
| spellingShingle | Hui Zhang Ang Li Yu-Fan Liu Zhong-Ming Sun Bing-Xin Jin Jia-Piao Lin Yan Yang Yong-Xing Yao Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats iScience Molecular biology Neuroscience Cell biology |
| title | Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats |
| title_full | Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats |
| title_fullStr | Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats |
| title_full_unstemmed | Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats |
| title_short | Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats |
| title_sort | spinal taok2 contributes to neuropathic pain via cgas sting activation in rats |
| topic | Molecular biology Neuroscience Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223018692 |
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