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. 2021 Nov 26;128(1):159–173. doi: 10.1016/j.bja.2021.10.020

Fig 3.

Fig 3

Systemic administration of CB-13 strongly inhibits nociceptive pain and inflammatory heat hypersensitivity in wild-type (WT) mice and in mice lacking peripheral mu-opioid receptors (MOR cKO) but weakly in CB1R cKO mice. (a) Systemic administration of CB-13 (5 mg kg−1, s.c.) significantly increased paw withdrawal latency (PWL) to radiant heat stimulation in both WT and MOR cKO mice at 60 min, but not in CB1R cKO mice (F2,52=5.23, P=0.009, two-way mixed-model anova). ∗P<0.05 vs pre-drug, #P<0.05 vs CB1R cKO, Bonferroni's post-test. (b) CB-13 (5 mg kg–1, s.c.) significantly decreased paw withdrawal frequency (PWF) to high-force (0.4 g) mechanical stimulation at 60 min in both WT and MOR cKO mice, but not in CB1R cKO mice (F2,52=13.89, P<0.001, two-way mixed model anova). ∗∗∗P<0.001 vs pre-drug; #P<0.05 vs CB1R cKO, Bonferroni's post-test (a, b: n=10/group, five/sex in each group). (c) Intraplantar injection of complete Freund's adjuvant (CFA; 20 μl, 1 mg ml−1) similarly increased paw thickness in WT and CB1R cKO mice (F2,114=393.7, P<0.001, two-way mixed model anova). ∗∗∗P<0.001 vs pre-CFA of WT, ###P<0.001 vs pre-CFA of CB1R cKO, n=30 mice/group, Bonferroni's post-test. (d) PWL to radiant heat stimulation was significantly decreased in the ipsilateral hind paw of both groups after intraplantar CFA injection (F6,152=20.26, P<0.001, two-way mixed model anova). ∗∗∗P<0.001 vs pre-CFA, n=20 mice/group, 10/sex, Bonferroni's post-test. (e) Effects of systemic CB-13 (5 mg kg−1, s.c.) on the ipsilateral PWL of mice at 72 h post-CFA (F6,78=6.4, P<0.001, two-way mixed-model anova). WT and CB1R cKO: n=10/group, five/sex; MOR cKO: n=9 mice. ∗P<0.05, ∗∗P<0.01, ∗∗∗P<0.001 vs pre-drug values; ###P<0.001, WT and MOR cKO vs CB1R cKO, Bonferroni's post-test. Data are shown as mean (standard error of the mean). Ipsi, ipsilateral; Contra, contralateral; anova, analysis of variance.