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Updated: Jul 16, 2025
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats
Hui Zhang1, Ang Li1,2, Yu-Fan Liu1
1Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, 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.
Insights
Thousand and one amino acid kinase 2 (TAOK2) activation in the spinal cord drives neuropathic pain after injury. Inhibiting TAOK2 or its downstream cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway alleviates pain hypersensitivity.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Thousand and one amino acid kinase 2 (TAOK2) is linked to neurodevelopmental disorders.
- The specific role of TAOK2 in neuropathic pain is not well understood.
- Chronic constriction injury (CCI) is a common model for inducing neuropathic pain.
Purpose of the Study:
- To investigate the role of TAOK2 in the development of neuropathic pain.
- To explore the relationship between TAOK2 activation and the cGAS-STING signaling pathway in pain.
- To identify potential therapeutic targets for neuropathic pain.
Main Methods:
- Assessed TAOK2 expression and activation in rat spinal dorsal horn after CCI.
- Examined the activation status of the cGAS-STING signaling pathway.
- Utilized TAOK2 gene silencing and pharmacological activation/inhibition.
- Investigated the effects of cGAS-STING pathway inhibition on CCI-induced hyperalgesia.
Main Results:
- TAOK2 was found to be enriched and activated in the spinal dorsal horn following CCI.
- CCI induced hyperalgesia and activated the cGAS-STING signaling pathway.
- Silencing TAOK2 reversed hyperalgesia and suppressed cGAS-STING activation.
- Pharmacological activation of TAOK2 in naive rats induced pain hypersensitivity and upregulated cGAS-STING signaling.
- Inhibition or silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia.
Conclusions:
- Spinal TAOK2 activation contributes to chronic constriction injury-induced neuropathic pain.
- The cGAS-STING signaling pathway is a key mediator in TAOK2-induced hyperalgesia.
- TAOK2 and the cGAS-STING pathway represent potential therapeutic targets for neuropathic pain management.
