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spinal interleukin-10 produces antinociception in neuropathy through microglial β-endorphin expression,separated from antineuroinflammation

Spinal interleukin-10 produces antinociception in neuropathy...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Hai-Yun Wu Xiao-Fang Mao Xue-Qi Tang Usman Ali Evhy Apryani Hao Liu Xin-Yan Li Yong-Xiang Wang King's Lab Shanghai Jiao Tong University School of Pharmacy

interleukin 10(IL-10) is antinociceptive in various animal models of pain without induction of tolerance,and its mechanism of action was generally believed to be mediated by inhibition of *** we reported that intrathecal IL-10 injection dose dependently attenuated mechanical allodynia and thermal hyperalgesiain male and female neuropathic rats,with ED50 values of 40.8 ng and24 ng,and Emax values of 61.5% MPE and 100% MPEin male *** with IL-10 specifically increased expression of theβ-endorphin(but not prodynorphin)gene and protein in primary cultures of spinal microglia but not in astrocytes or *** injection of IL-10 stimulated β-endorphin expression from microglia but not neurons or astrocytes in both contralateral and ipsilateral spinal cords of neuropathic ***,intrathecal injection of the β-endorphin neutralizing antibody,opioid receptor antagonist naloxone,or μ-opioid receptor antagonist CTAP completely blocked spinal IL-10-induced mechanical antiallodynia,while the microglial inhibitor minocycline and specific microglia depletor reversed spinal IL-10-induced β-endorphin overexpression and mechanical ***-10 treatment increased spinal microglial STAT3 phosphorylation,and the STAT3 inhibitor NSC74859 completely reversed IL-10-increased spinal expression ofβ-endorphin and neuroinflammatory cytokines and mechanical *** of the Bcl3 and Socs3 genes nearly fully reversed IL-10-induced suppression of neuroinflammatory cytokines(but not expression of β-endorphin),although it had no e□ect on mechanical *** contrast,disruption of the POMC gene completely blocked IL-10-stimulated β-endorphin expression and mechanical antiallodynia,but had no e□ect on IL-10 inhibited expression of neuroinflammatory *** this study revealed that IL-10 produced antinociception through spinal microglialβendorphin expression,but not inhibition of neuroinflammation.

关键词： endorphin expression,separated from antineuroinflammation spinal interleukin-10 produces antinociception in neuropathy through microglial

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