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. 2013 Sep 12;8(9):e74706. doi: 10.1371/journal.pone.0074706

Figure 6. Conditional mu-cKO mice show decreased opiate-induced analgesia in the CFA-induced inflammatory pain model.

Figure 6

(A) Two days after CFA, morphine (i.p.) dose-dependently reduced heat and mechanical hypersensitivities in mufl control mice. This analgesia was diminished in mu-cKO mice. Dashed lines represent baseline (pre-CFA) sensitivities. White bars, mufl mice; black bars, mu-cKO mice. For plantar test, n=13-20/genotype. two-way ANOVA (genotype x treatment F(1,90) = 75.336, P <0.001 for treatment; F(1,90) = 23.313, P <0.001 for genotype. Post-hoc Bonferroni test, ✰✰✰ P<0.001, morphine vs saline; ★★ P<0.01, ★★★ P<0.001 cKO vs flox controls. For Von Frey filaments test, n=7-18/genotype. two-way ANOVA (genotype x treatment F(1,91) = 41.573, P <0.001 for treatment; F(1,91) = 27.378, P <0.001 for genotype. Post-hoc Bonferroni test, ✰✰ P<0.01, ✰✰✰ P<0.001 morphine vs saline; ★ P<0.05, ★★ P<0.01 mu-cKO vs mufl controls. (B) Fentanyl produced a dose-dependent analgesia in mufl control mice 2 days after CFA. Mu-cKO mice displayed a decreased analgesic response in the mechanical sensitivity test for the 0.03 mg/kg fentanyl dose. n=5-10/genotype. For plantar test, two-way ANOVA (genotype X treatment F(1,54) = 8.979, P <0.001 for treatment, P= 0.19 for genotype), post-hoc Bonferroni test; ✰✰ P <0.01, ✰✰✰ P<0.001, fentanyl 0.1 mg/kg vs saline; for fentanyl 0.03 mg/kg, P = 0.0675 in mufl animals, P = 0.21 in mu-cKO animals. For Von Frey test, two-way ANOVA (genotype X treatment F(1,45) = 22.802, P <0.001 for treatment, F(1,45) = 9.316, P <0.01 for genotype). Post-hoc Bonferroni test for treatment, ✰✰✰ P<0.001, fentanyl 0.1 mg/kg vs saline; for fentanyl 0.03 mg/kg, P = 0.0575 mufl animals, P = 0.28 mu-cKO animals. Post-hoc Fisher test for genotype, ★ P<0.05, mu-cKO vs mufl mice. (C) Morphine-induced analgesia is reduced by systemic administration of the peripheral antagonist naloxone methiodide (NM). Morphine (5 mg/kg) induced an antihyperalgesic effect in mufl mice for both heat and mechanical responses. Systemic NM diminished morphine-induced analgesia. Heat hypersensitivity, one-way ANOVA for treatment F(3,42) = 29.778, P<0.001 ; post-hoc Bonferroni test, ✰✰ P <0.01, ✰✰✰ P <0.001 morphine vs saline; ★★ P<0.01 ★★★ P<0.001 NM + morphine vs morphine. Mechanical hypersensitivity, one-way ANOVA for treatment F(3,52) = 23.467, P<0.001 ; post-hoc Bonferroni test, ✰✰✰ P <0.001 morphine vs saline; ★★★ P<0.001 NM + morphine vs morphine.