Figure 3

Antinociceptive effect of systemic FF6 in the unilateral CFA-induced hindpaw inflammation. (A–D) Elevation of PPT after intravenous (i.v.) injection of fentanyl (Fen) (A,B) and FF6 (C,D) in inflamed (A,C) and noninflamed (B,D) hindpaws, assessed before (Basal) and 4 days after i.pl. CFA application (0) at 10 to 60 min after injection of fentanyl or FF6. ^§P < 0.01, ⁺P < 0.001 vs^. corresponding baseline threshold (Basal) before CFA injections, paired t-test or Wilcoxon test; ^#P < 0.05, ^*P < 0.001 vs. vehicle, two-way RM ANOVA and Bonferroni test (n = 8–10). (E–L) Effects of antagonists on PPT elevations produced 10 min after i.v. injection of fentanyl (E–H) or FF6 (I–L) (each at 16 µg/kg). Naloxone hydrochloride (NLX, 2 mg/kg) or vehicle (Veh) were injected subcutaneously (s.c.) (E,G,I,K). Naloxone methiodide (NLXM, 50 µg) or vehicle (Veh) were injected intraplantarly (i.pl.) into both hindpaws (F,H,J,L). ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 NLXM or NLX + Fen or FF6 vs. Veh + Fen or FF6, unpaired t-test; ⁺⁺P < 0.01, ⁺⁺⁺P < 0.0001 vs. corresponding baseline thresholds (dashed lines) evaluated 4 days after CFA, but before any injections; paired t-test or Wilcoxon test (n = 10 animals per condition for all except vehicle in J and L (n = 8)). Data are presented as mean ± SEM.