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Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats

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Abstract

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BoNT/A:

Botulinum toxin A

CCI:

Chronic constriction injury

pMWT:

Paw mechanical withdrawal threshold

pTWL:

Paw thermal withdrawal latency

LC3:

Microtubule-associated protein-1 light chain 3

NLRP3:

NOD-like receptor family pyrin domain-containing 3

SNAP-25:

Synaptosomal-associated protein 25 kDa

LTP:

Long-term potentiation

NMDAR:

N-methyl-d-aspartate receptors

SD:

Sprague Dawley

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Acknowledgements

We are very grateful to our corporate sponsor Lanzhou Biotechnique Development Co., LTD.

Funding

This study was supported by grants from the Natural Science Foundation of Guangdong Province (2021A1515010313), the Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases (2020B1212060017), Guangdong Provincial Clinical Research Center for Neurological Diseases (2020B1111170002), Southern China International Joint Research Center for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003 and 2020A0505020004), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease, Guangzhou Clinical Research and Translational Center for Major Neurological Diseases (201604020010), Guangzhou Science and Technology Program (20220610195), a crosswise project of First Affiliated Hospital, Sun Yat-sen University (2020027).

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Author notes

  1. Juan-juan He and Xiao-mei Wei have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, China

    Juan-juan He, Meng-li Wu, Zu-biao Song & Wei-xi Zhang

  2. Department of Rehabilitation, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China

    Juan-juan He & Xiao-mei Wei

  3. Department of Rehabilitation, The Sixth Affiliated Hospital, Sun Yat-Sen University, No. 26 Tianhe Yuancun Cross Road 2, Guangzhou, 510655, China

    Li Jiang

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Contributions

All authors contributed to the study conception and design. Conceived and designed the experiments: WZ and LJ. Material preparation, data collection and analysis: JH, MW and ZS. Wrote the paper: JH and XW. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li Jiang or Wei-xi Zhang.

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Ethical Approval

This study was approved by Institutional Animal Care and Use Committee, Sun Yat-Sen University (Approval NO. SYSU-IACUC-2022-000798).

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He, Jj., Wei, Xm., Wu, Ml. et al. Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats. Neurochem Res 48, 2161–2174 (2023). https://doi.org/10.1007/s11064-023-03893-0

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  • DOI: https://doi.org/10.1007/s11064-023-03893-0

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