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Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity

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Abstract

The mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Therefore, in the current study, we investigated the synaptic delivery of spinal KA receptor subunits and the interaction between KA receptor subunits and glutamate receptor-interacting protein (GRIP) during the postoperative pain. Our data indicated that plantar incision induced the synaptic delivery of GluK2, but not GluK1 or GluK3 in ipsilateral spinal cord dorsal horns. The co-immunoprecipitation showed an increased GluK2 –GRIP interaction in ipsilateral dorsal horn neurons at 6 h post-incision. Interestingly, Intrathecal pretreatment of GRIP siRNA increased the paw withdrawal thresholds to mechanical stimuli and decreased the cumulative pain scores in the paws ipsilateral to the incision at 6 h post-incision. Additionally, Intrathecal pretreatment of GRIP siRNA reduced the synaptic abundance of GluK2 in ipsilateral spinal dorsal horn at 6 h after plantar incision. In general, our data have demonstrated that the GluK2- GRIP interaction-mediated synaptic abundance of GluK2 in dorsal horn neurons plays an important role in the postoperative pain hypersensitivity. Disrupting the GluK2- GRIP interaction may provide a new approach for relieving postoperative pain.

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (81771181, 81571065); the Beijing Natural Science Foundation (7202053); Beijing Hospitals Authority Youth Program (QML20180105); and Scientific Research Common Program of Beijing Municipal Commission of Education (KM201910025018).

Funding

This work was supported by Grants from the National Natural Science Foundation of China (81771181, 81571065); the Beijing Natural Science Foundation (7202053); Beijing Hospitals Authority Youth Program (QML20180105); and Scientific Research Common Program of Beijing Municipal Commission of Education (KM201910025018).

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Author notes

  1. Ruijuan Guo and Huili Li equally contributed to the work

Authors and Affiliations

  1. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Ruijuan Guo

  2. Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Beijing, 100020, China

    Huili Li, Rong Shi & Yun Wang

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  1. Ruijuan Guo
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  2. Huili Li
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Contributions

RG: Investigation, writing—original draft, methodology. HL: Data curation, methodology, visualization, investigation. RS: Data curation, visualization, conceptualization, methodology. YL: Conceptualization, data curation, methodology. YW: Writing—review & editing, supervision, conceptualization.

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Correspondence to Yun Wang.

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The authors declare no conflict of interest.

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All experiments were reviewed and approved by the Ethical Committee of Beijing Chaoyang Hospital, Capital Medical University (Beijing, China) (Approval No. 2018-381).

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Guo, R., Li, H., Shi, R. et al. Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity. Neurochem Res 46, 1771–1780 (2021). https://doi.org/10.1007/s11064-021-03323-z

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