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. 2019 Dec 26;17(2):722–742. doi: 10.1007/s13311-019-00800-w

Fig. 8.

Fig. 8

Effects of TLR4/NF-κB signaling activation on the expression of HMGB1 in the spinal cord and the development of morphine tolerance and hyperalgesia. (a) Repeated i.t. coinjections of morphine with TAK-242 inhibited the phosphorylation of NF-κB p65 and reduced HMGB1 expression. (b) Repeated i.t. coinjections of morphine with PDTC reduced HMGB1 expression. Data shown in (a) and (b) are presented as the mean ± SEM and were analyzed by one-way ANOVA. * P < 0.05, ** P < 0.01 vs. control (i.t. saline containing 10% DMSO); # P < 0.05, ## P < 0.01 vs. morphine plus vehicle group. (c) Repeated i.t. coinjections of morphine plus TAK-242 dose-dependently prevented the decrease in morphine’s MPAE. ### P < 0.001 vs. day one (two-way ANOVA); * P < 0.05, ** P < 0.01, *** P < 0.001 vs. morphine plus vehicle group (one-way ANOVA). Repeated i.t. injections of saline or TAK-242 alone did not change the basal MPAE value. (d, e) Chronic i.t. morphine exposure resulted in decreased paw withdrawal threshold (PWT) (d) and paw withdrawal latency (PWL) (e) in the left hind paw. ## P < 0.01 vs. baseline. Repeated i.t. coinjections of morphine plus TAK-242 prevented the reduction in PWT and PWL after morphine withdrawal. * P < 0.05; ** P < 0.01 vs. morphine plus vehicle group (Student’s t-test). The basal tail-flick response, PWT and PWL were not changed by repeated i.t. injections of TAK-242 alone.