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Sinomenine attenuates chronic inflammatory pain in mice

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Abstract

Sinomenine, an alkaloid originally isolated from the roots of Sinomeniumacutum, is used as a traditional Chinese medicine for rheumatic arthritis. However, little is known about the neuronal mechanisms underlying the analgesic effects of sinomenine in animals with chronic inflammatory pain. In this study, we investigated the persistent inflammatory pain induced by hind paw injection of complete Freund’s adjuvant (CFA) in mice, which was reversed by sinomenine administration. In the anterior cingulate cortex (ACC), a region highly associated with chronic pain processing, the upregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors and Ca2+/calmodulin-dependent protein kinase II, total levels of GluA1, and phosphorylation of GluA1 at Ser831 (p-GluA1-Ser831) were reversed by systemically administrating sinomenine. Furthermore, sinomenine treatment downregulated the mammalian target of rapamycin (mTOR) pathway. Increases in p-mTOR, p-p70S6k, p-S6, and p-4EBP, which were induced by chronic inflammation, were all changed. However, sinomenine did not affect the levels of GluN2A-containing NMDA receptors and p-GluA1-Ser845, as well as the total levels of mTOR, p70S6k, S6, and 4EBP. In conclusion, results indicated that sinomenine reduced the chronic inflammatory pain induced by CFA, at least partially by regulating the GluN2B receptors and mTOR signals in the ACC.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China No. 81325022, and Clinical Science and Technology Project Funding in Jiangsu Province (No. BL2012002).

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China

    Shuo Li, Jing Han, Qi Yang, Bin Feng, Le Yang & Ming-gao Zhao

  2. Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing, 210002, China

    Dong-sheng Wang, Wen-bo Kang & Gang Liu

Authors
  1. Shuo Li
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  2. Jing Han
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  3. Dong-sheng Wang
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  4. Qi Yang
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  5. Bin Feng
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  6. Wen-bo Kang
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  7. Le Yang
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  8. Gang Liu
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  9. Ming-gao Zhao
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Correspondence to Gang Liu or Ming-gao Zhao.

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Shuo Li, Jing Han, Dong-sheng Wang contribute equally to this work.

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Li, S., Han, J., Wang, Ds. et al. Sinomenine attenuates chronic inflammatory pain in mice. Metab Brain Dis 32, 211–219 (2017). https://doi.org/10.1007/s11011-016-9889-8

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  • DOI: https://doi.org/10.1007/s11011-016-9889-8

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