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Fig. 6 | Journal of Neuroinflammation

Fig. 6

From: Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord

Fig. 6

CaMKKβ-dependent AMPK activation is required in the lidocaine-mediated SOCS3 upregulation. a Lidocaine increased the levels of SOCS3 in the spinal cord. Lidocaine (100, 200, and 400 μg/10 μL, i.t.) was intrathecally administered once daily for 7 days. After the final administration, spinal samples were collected and evaluated by immunoblot assay (n = 4). b Lidocaine (0.001 to 10 μM) promoted phosphorylation of AMPK in a concentration-dependent manner in BV-2 cells. Cells were collected and analyzed 12 h after lidocaine treatment. c Compound C (20 μM) administration reversed lidocaine-induced upregulation of SOCS3. d STO-609 administration (20 μM, 2 h) prior to lidocaine administration (10 μΜ, 12 h) prevented the lidocaine-induced AMPK phosphorylation and SOCS3 expression. e, f Extracellular Ca2+ depletion with EGTA (2 mM) or intracellular Ca2+ depletion with BAPTA-AM (10 μM) abolished the increasing of SOCS3 and AMPK phosphorylation induced by lidocaine. BV-2 cells were pretreated with Ca2+ chelator for 30 min, followed by 10 μM lidocaine treatment for 12 h. g Lidocaine markedly inhibited the cAMP levels in BV-2 cells. Cells were collected and analyzed 12 h after lidocaine treatment (n = 6). h Lidocaine markedly inhibited the phosphorylation of PKA in BV-2 cells. Cells were collected and analyzed 12 h after lidocaine treatment. i, j Representative Ca2+ tracings and group data showed that lidocaine had no marked effect on [Ca2+]i within 1500 min in BV-2 cells. k Lidocaine had no marked effect on [Ca2+]i in BV-2 cells at 1, 4, and 8 h after treatment. l, m Lidocaine had no effect on Socs3 mRNA in vivo (n = 3) and in vitro. (bf, hk, m Data were obtained from three independent experiments). *p < 0.05, **p < 0.01, and ***p < 0.001 versus the vehicle group; # p < 0.05 and ## p < 0.01 versus the morphine-treated group or lidocaine-treated group

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