Opening KATP Channels Induces Inflammatory Tolerance and Prevents Chronic Pain Article Swipe
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· 2021
· Open Access
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· DOI: https://doi.org/10.21203/rs.3.rs-1100650/v1
· OA: W4200496237
<title>Abstract</title> <bold>Background:</bold> Current treatments for chronic pain are not satisfactory, prompting a frantic search for new therapeutics and new therapeutic targets. Our previous study indicates K<sub>ATP</sub> channel opener has analgesic effect, but the mechanism has not been elucidated. We speculated that K<sub>ATP</sub> channel opener may increase suppressor of cytokine signaling (SOCS)-3 expression to induce inflammatory tolerance and attenuate chronic pain. <bold>Methods: </bold>The plantar incision (PI) surgery-induced postoperative pain was performed to establish chronic pain model. Growth arrest–specific 6 (Gas6)<sup>-/-</sup> and Axl<sup>-/-</sup> mice were used for signaling research. The microglia cell line BV-2 was cultured for <italic>in vitro</italic> experiments.<bold>Results: </bold>K<sub>ATP</sub> channel opener significantly attenuated incision-induced mechanical allodynia in mice, associated with the up-regulated expression of SOCS3. Opening K<sub>ATP</sub> channels induced the expression of SOCS3 dependent on Gas6/Axl signaling pathway in microglia. Opening K<sub>ATP</sub> channels inhibits incision-induced mechanical allodynia by activating Gas6/Axl-SOCS3 signaling pathway. Opening K<sub>ATP</sub> channels induces inflammatory tolerance to relieve neuroinflammation and postoperative pain.<bold>Conclusions:</bold> We demonstrated that K<sub>ATP</sub> channel opening activated Gas6/Axl/SOCS3 signaling to induce inflammatory tolerance and relief chronic pain. We explored a new target for anti-inflammatory and analgesia by regulating the innate immune system, and provide a theoretical basis for clinical preemptive analgesia.
