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Withdrawal from spinal application of remifentanil induces long-term potentiation of c-fiber-evoked field potentials by activation of Src family kinases in spinal microglia

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Abstract

It is well known that remifentanil, a widely used intravenous anesthesia drug, can paradoxically induce hyperalgesia. The underlying mechanisms are still not clear despite the wide investigations. The present study demonstrated that withdrawal from spinal application of remifentanil could dose-dependently induce long term potentiation (LTP) of C-fiber evoked field potentials. Remifentanil withdrawal could activate Src family kinases (SFKs) in microglia, and upregulate the expression of tumor necrosis factor alpha (TNFα) in spinal dorsal horn. Furthermore, pretreatment with either microglia inhibitor Minocycline, SFKs inhibitor PP2 or TNF αneutralization antibody could block remifentanil withdrawal induced spinal LTP, whereas supplement of recombinant rat TNFα to the spinal cord could reverse the inhibitory effect of Minocycline or PP2 on remifentanil withdrawal induced LTP. Our results suggested that TNFαrelease following SFKs activation in microglia is involved in the induction of LTP induced by remifentanil withdrawal.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation (Beijing, People’s Republic of China. Nos. 81200856 and 81471250); Nature Science Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China. Nos. 2014A030313029), and by Scientific Research Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China. No. 2016A020215035). All grants were awarded to Dr. Wei.

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  1. Tao Yang and Sujuan Du have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, SunYat-SenMemorial Hospital, SunYat-Sen University, 107 Yanjiang Xi Road, Guangzhou, People’s Republic of China

    Tao Yang, Sujuan Du & Xijiu Ye

  2. Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China

    Xianguo Liu & Xuhong Wei

  3. Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, People’s Republic of China

    Xianguo Liu & Xuhong Wei

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  1. Tao Yang
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Correspondence to Xijiu Ye or Xuhong Wei.

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Yang, T., Du, S., Liu, X. et al. Withdrawal from spinal application of remifentanil induces long-term potentiation of c-fiber-evoked field potentials by activation of Src family kinases in spinal microglia. Neurochem Res 43, 1660–1670 (2018). https://doi.org/10.1007/s11064-018-2582-z

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