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. 2014 May 13;9(5):e97361. doi: 10.1371/journal.pone.0097361

Figure 4. Ultra-low dose naloxone non-stereoselectively inhibited morphine-induced hyperalgesia in control and TLR4 mutant mice.

Figure 4

(A,C) Mice were administered treatments (i.p.) twice daily, with mechanical thresholds measured daily prior to the morning injection. Number of paw withdrawals in (A) control (C3H/HeOuJ) and TLR4 mutant (C3H/HeJ) mice or (C) control (B10ScSNJ) and TLR4 null (B10ScNJ) mice treated with morphine, morphine and (+)naloxone (NLX), or vehicle (saline). A small but significant increase was observed with saline treatment over time within control and TLR4 mutant mice (p<0.01 and p<0.05, respectively) (A). (B,D) The mean number of paw withdrawals per treatment group on Day 7 in (B) TLR4 mutant (C3H/HeJ) and (D) null (B10ScNJ) mice vs respective control strains. Morphine significantly increased mechanical hyperalgesia in all genotypes. Co-administration of (−) or (+)naloxone (NLX) blocked morphine-induced hyperalgesia in control and TLR4 mutant and null mice. Data represent means for n = 7–11 per group. Statistical analyses were performed using a two-way ANOVA followed by Bonferroni post hoc test. The asterisk denotes a significant difference from saline-treated mice. *** = p<0.001. The ψ denotes a significant difference between genotypes receiving saline treatment. ψ ψ ψ = p<0.001.