Paeoniflorin attenuates chronic constriction injury-induced neuropathic pain by suppressing spinal NLRP3 inflammasome activation

Abstract

Neuropathic pain remains one of the most common pain conditions worldwide. Accumulating evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome contributes to the pathogenesis of neuropathic pain, although the role of the NLRP3 inflammasome in neuropathic pain has not yet been fully elucidated. In animal models of neuropathic pain, paeoniflorin (PF) was shown to have analgesic, anti-inflammatory, and antidepressant effects. However, the role of the NLRP3 inflammasome in the analgesic properties of PF has not yet been studied. In this study, we aimed to confirm whether activation of the NLRP3 inflammasome in the spinal cord was involved in the development of neuropathic pain and whether PF could be an effective treatment for this type of pain. We found that activation of the NLRP3 inflammasome mediated the development of neuropathic pain following chronic constriction injury of the sciatic nerve and that PF attenuated neuropathic pain by inhibiting NLRP3 inflammasome activation. Moreover, PF enhanced the translocation of the transcription factor nuclear factor erythroid 2-related factor 2 into the nucleus and suppressed nuclear factor-kappa B activity in the spinal cord. These results suggest that PF may be a potential therapeutic agent for neuropathic pain.

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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (No. 81703736), Key Discipline Construction Projects of Higher School, Hebei Province Natural Science Foundation of China (No. H2018406038), Science and Technology Research Youth Fund Project of Higher School in Hebei Province (No. QN2019167), and Hebei Province Medical Science Research Key Project (No. 20181140).

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JZ conceived and designed the study and wrote the manuscript. PL and JC designed and performed most of the experiments. SM carried out the animal experiments and helped to revise the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jianyu Zhou.

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All animal experiments were reviewed and approved by the Chengde Medical University Animal Care Committee (Approval No. CDMULAC-20180410016) and complied with the International Association for the Study of Pain (IASP) Guidelines for the Use of Animals in Research.

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Liu, P., Cheng, J., Ma, S. et al. Paeoniflorin attenuates chronic constriction injury-induced neuropathic pain by suppressing spinal NLRP3 inflammasome activation. Inflammopharmacol (2020). https://doi.org/10.1007/s10787-020-00737-z

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Keywords

  • NLRP3
  • Inflammasome
  • Caspase-1
  • Neuropathic pain
  • Nrf2
  • Paeoniflorin