Abstract
Lidocaine is one of the typical local anesthetics that are frequently used in the peripheral nerve blocks and pain management. Emerging evidence have shown that lidocaine may exert anti-inflammatory effect involving neuropathic pain. However, the effect and underlying mechanism of lidocaine in suppressing neuroinflammation in neuropathic pain are incompletely revealed. In this study, effects of lidocaine on the suppressors of cytokine-signaling protein 3 (SOCS3) in microglia are investigated in chronic constriction injury (CCI) rat model and lipopolysaccharide (LPS)-stimulated BV-2 cells. It was shown that intrathecal injection of lidocaine substantially alleviated CCI-induced neuropathic pain, as reflected by the decreased thermal latency and mechanical threshold. Lidocaine reduced the CCI-evoked spinal injury and cell apoptosis. CCI induced an significant increase of IBA1+ microglia accompanied by the increase of inflammatory cytokines IL-6 and IL-1β, which were suppressed after lidocaine administration. SOCS3 expression in IBA1+ microglia was notably upregulated in response to lidocaine injection, which presented in a similar pattern in LPS-activated BV-2 cells. Furthermore, lidocaine upregulated SOCS3 expression dependent of pCREB, and CREB silencing greatly discounted this effect. The intrathecal injection of lentiviral vectors LV-SOCS3 efficiently alleviated CCI-evoked neuropathic pain and reduced spinal IBA1+ microglia. SOCS3 overexpression contributed to the inhibition of neuroinflammation by decreasing the expression and activation of p38 MAPK and NF-κB stimulated by LPS. Collectively, lidocaine promoted the SOCS3 expression in microglia, in turn leading to suppression of IBA1+ microglia accumulation and p38 MAPK and NF-κB, which may expand our understanding on lidocaine in suppressing neuroinflammation and neuropathic pain.
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YZ and SBY conceived and designed the study; YZ drafted the manuscript and conducted the experiments. XHH analyzed and interpreted the data; SBY critically revised the manuscript; All authors have read and approved the final manuscript.
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Zheng, Y., Hou, X. & Yang, S. Lidocaine Potentiates SOCS3 to Attenuate Inflammation in Microglia and Suppress Neuropathic Pain. Cell Mol Neurobiol 39, 1081–1092 (2019). https://doi.org/10.1007/s10571-019-00703-6
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DOI: https://doi.org/10.1007/s10571-019-00703-6