Figure 3

Effects of i.v. fentanyl and NFEPP on heat hyperalgesia in mice inoculated with live B16-F10 cells. (A) Dose–response effects of fentanyl and NFEPP (both at 10–100 nmol/kg) (n = 6 in NFEPP 30 nmol/kg group, n = 5 per group for other treatments). (B) Systemic naloxone (NLX; 1 mg/kg s.c. at the neck), but not peritumoral naloxone-methiodide (NLX-MET; 1 µg local), inhibited the effect of i.v. fentanyl (F; 30 nmol/kg). Both NLX (1 mg/kg) and NLX-MET (0.1–1 µg) reversed the effect of NFEPP (NF; 100 nmol/kg). NLX-MET (1 µg local) had no effect when injected into non-inoculated, contralateral limb (CL) (n = 6 in solvent [SOL] group, n = 8 in F + NLX-MET group, n = 5 per group for other treatments). (C) Peritumoral NLX-MET (1 µg local) did not modify antinociceptive effects evoked by high doses of fentanyl (F; 100 nmol/kg) or NFEPP (NF; 1000 nmol/kg) (n = 6 in SOL + NLX-MET and F + NLX-MET groups, n = 5 per group for other treatments). (D) Cyprodime (CYP; 1 mg/kg), but not naltrindole (NTI; 0.1 mg/kg) or nor-binaltorphimine (n-BNI; 10 mg/kg), injected s.c. at the neck, inhibited the effects of NF (100 nmol/kg) (n = 5 per group). In (A,B), ^●●P < 0.01 compared to the corresponding left paw, unpaired Student’s t test; **P < 0.01 compared to solvent (SOL)-treated mice, one-way ANOVA and Dunnett’s t test. In (C,D), ^●●P < 0.01 compared to the corresponding left paw, unpaired Student’s t test; **P < 0.01 compared to the corresponding paw in solvent (SOL)-treated mice, two-way ANOVA and Tukey’s test. All data are means ± SEM. For clarity, in the graphs a maximal number of two symbols of significancy are represented (the exact values are stated in the results section).