Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats

Hui Zhang; Ang Li; Yu-Fan Liu; Zhong-Ming Sun; Bing-Xin Jin; Jia-Piao Lin; Yan Yang; Yong-Xing Yao

doi:10.1016/j.isci.2023.107792

Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats

iScience. 2023 Aug 30;26(10):107792. doi: 10.1016/j.isci.2023.107792. eCollection 2023 Oct 20.

Authors

Hui Zhang¹, Ang Li^{1

2}, Yu-Fan Liu¹, Zhong-Ming Sun¹, Bing-Xin Jin¹, Jia-Piao Lin¹, Yan Yang^{3

4}, Yong-Xing Yao¹

Affiliations

¹ Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
² Department of Anesthesia, People's Hospital of Guizhou Province, Guiyang, Guizhou 550025, China.
³ Department of Neurobiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China.
⁴ Centre for Neuroscience, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

Abstract

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.

Keywords: Cell biology; Molecular biology; Neuroscience.