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Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord

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Summary

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Tao Feng  (冯 涛), Ze-lin Weng  (翁泽林), Jian-cheng Zhang  (张建成) & Shi-ying Yuan  (袁世荧)

  2. Department of Anesthesiology, Xixiang people’s Hospital of Bao’an District, Shenzhen, 518100, China

    Tao Feng  (冯 涛) & Kun-feng Wang  (王昆锋)

  3. Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Jiangsu Province Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China

    Qin Yin  (殷 琴) & Wei Cheng  (程 伟)

Authors
  1. Tao Feng  (冯 涛)
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  2. Qin Yin  (殷 琴)
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  3. Ze-lin Weng  (翁泽林)
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  4. Jian-cheng Zhang  (张建成)
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  5. Kun-feng Wang  (王昆锋)
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  6. Shi-ying Yuan  (袁世荧)
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  7. Wei Cheng  (程 伟)
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Corresponding authors

Correspondence to Shi-ying Yuan  (袁世荧) or Wei Cheng  (程 伟).

Additional information

The two authors contributed equally to the project.

This project was supported by grants from the National Natural Science Foundation of China (Nos. 31100801 and 81200858).

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Feng, T., Yin, Q., Weng, Zl. et al. Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 830–837 (2014). https://doi.org/10.1007/s11596-014-1361-6

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  • DOI: https://doi.org/10.1007/s11596-014-1361-6

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