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. 2020 Sep 24;13:571–582. doi: 10.2147/JIR.S266995

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© 2020 Wang et al.

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A438079 prevented the development of morphine antinociceptive tolerance and inhibited the morphine-tolerant-induced upregulation of NLRP3. (A) Western blot showing the expression of P2X7R and NLRP3 in the spinal cord of mice treated with saline (CON), morphine (MOR), A438079+morphine (A+MOR) and A438079. (B) Columns and errors are presented as mean ± SEM; n = 6, **p<0.01, ***p < 0.001. (C) The withdrawal latencies of WT mice treated with morphine, A438079+morphine or 25%DMSO+Morphine before and 30 min after morphine treatment. (D) The %MPE of WT mice treated with morphine or A438079+morphine on days 1 and 7. Columns and errors are presented as mean ± SEM; n = 6, ***p<0.001. (E) Repeated morphine treatment produced a significant rightward shift in the morphine dose-response curve on day 8. A438079 pretreated mice showed elevated response to morphine, and morphine response curve was shifted to the left. The ID₅₀ of morphine in mice treated with morphine and treated with A438079+morphine on day8 were 29.04 ug and 7.254ug (n=6). (F) P2X7R (red) colocalization with Iba1 (green) in the dorsal horn of spinal cord of WT mice treated with morphine.