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Salidroside Alleviates Chronic Constriction Injury-Induced Neuropathic Pain and Inhibits of TXNIP/NLRP3 Pathway

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Abstract

Neuropathic pain is one of the most common conditions requiring treatment worldwide. Salidroside (SAL), a phenylpropanoid glucoside extracted from Rhodiola, has been suggested to produce an analgesic effect in chronic pain. However, whether SAL could alleviate pain hypersensitivity after peripheral nerve injury and its mode of action remains unclear. Several studies suggest that activation of the spinal NOD-like receptor protein 3 (NLRP3) inflammasome and its related proteins contribute to neuropathic pain’s pathogenesis. This study investigates the time course of activation of spinal NLRP3 inflammasome axis in the development of neuropathic pain and also whether SAL could be an effective treatment for this type of pain by modulating NLRP3 inflammasome. In the chronic constriction injury (CCI) mice model, spinal NLRP3 inflammasome-related proteins and TXNIP, the mediator of NLRP3, were upregulated from the 14th to the 28th day after injury. The TXNIP and NLRP3 inflammasome-related proteins were mainly present in neurons and microglial cells in the spinal dorsal horn after CCI. Intraperitoneal injection of SAL at 200 mg/kg for 14 consecutive days starting from the 7th day of CCI injury could ameliorate mechanical and thermal hypersensitivity in the CCI model. Moreover, SAL inhibited the activation of the TXNIP/NLRP3 inflammasome axis and mitigated the neuronal loss of spinal dorsal horn induced by nerve injury. These results indicate that SAL could produce analgesic and neuroprotective effects in the CCI model of neuropathic pain.

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Data Availability

The datasets generated for this study are available on request to the corresponding author.

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Funding

This work was supported by National Natural Science Foundation of China (Grant No. 81971037 to F. Yang) the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201910025026 to F. Yang) and Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan CIT&TCD201904092 (QL).

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Authors and Affiliations

  1. Department of Neurobiology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Fengtai District, Beijing, 100069, China

    Tingting Hu, Qingyu Sun, Yurui Zhang, Yumeng Ding, Yiran Ma, Jing Liu, Wen Chen, Peipei Wang & Fei Yang

  2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China

    Ting Lan & Qian Li

  3. Department of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, China

    Yu Gou

Authors
  1. Tingting Hu
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  2. Qingyu Sun
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  3. Yu Gou
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  4. Yurui Zhang
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  9. Ting Lan
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  10. Peipei Wang
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  11. Qian Li
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  12. Fei Yang
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Contributions

FY and TH designed the overall approach, coordinated the study, and drafted the manuscript. TH, QL, and FY prepared the manuscript. TH did most of the behavioral, Western blot and immunostaining studies and statistical analysis of the data. QS, YG, YZ, YD, YM, JL, WC and TL contributed to the design of the different experiments and executed a number of them. PW provided critical analysis of the experiments and the results. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fei Yang.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical Approval

The animal study was reviewed and approved by the Capital Medical University Animal Care and Use Committee.

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Hu, T., Sun, Q., Gou, Y. et al. Salidroside Alleviates Chronic Constriction Injury-Induced Neuropathic Pain and Inhibits of TXNIP/NLRP3 Pathway. Neurochem Res 47, 493–502 (2022). https://doi.org/10.1007/s11064-021-03459-y

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  • DOI: https://doi.org/10.1007/s11064-021-03459-y

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