Zhang Hui, Li Ang, Liu Yu-Fan, Sun Zhong-Ming, Jin Bing-Xin, Lin Jia-Piao, Yang Yan, Yao Yong-Xing
Department 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, China.
iScience. 2023 Aug 30;26(10):107792. doi: 10.1016/j.isci.2023.107792. eCollection 2023 Oct 20.
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.
千一氨基酸激酶2（TAOK2）是哺乳动物无菌20激酶家族的成员，与神经发育障碍有关；然而，其在神经性疼痛中的作用尚不清楚。在此，我们发现TAOK2在大鼠脊髓背角慢性压迫损伤（CCI）后富集并被激活。同时，环磷酸鸟苷-磷酸腺苷合酶（cGAS）-干扰素基因刺激因子（STING）信号通路也随着痛觉过敏而被激活。沉默TAOK2可逆转痛觉过敏，并抑制CCI诱导的cGAS-STING信号通路的激活，而TAOK2的药理学激活则在未处理的大鼠中诱导疼痛超敏反应并上调cGAS-STING信号通路。此外，cGAS-STING信号通路的药理学抑制或基因沉默可减轻CCI诱导的痛觉过敏。综上所述，这些数据表明脊髓TAOK2的激活通过cGAS-STING信号通路的激活导致CCI诱导的痛觉过敏，为神经性疼痛的治疗提供了新的分子靶点。
