B vitamins increase the analgesic effect of ketorolac in the formalin test in the rat

The purpose of this study was to assess the possible synergistic interaction between ketorolac and B-vitamins in the rat formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 μl of diluted formalin (1%). Reduction of the number of flinches was considered as antinociception. Ketorolac (0.32-10 mg/kg, po), B-vitamins (56-316 mg/kg), or a combination of B-vitamins (either 100:100:1 or 100:100:5 proportion of vitamin B₁, B₆ and B₁₂, respectively) and ketorolac was administered orally and the antinociceptive effect was determined, Isobolographic analyses were used to define the nature of the functional interactions between B-vitamins and ketorolac in a proportion (0.5:0.5, ketorolac:B-vitamins). Ketorolac (ED₂₅ 3.5 ± 0.7 mg/kg), B-vitamins in a 100:100:1 (ED₂₅ 277.1 ± 30.2 mg/kg) or 100:100:5 (ED₂₅157.3 ± 13.7 mg/kg) proportion and fixed-ratio B-vitamins-ketorolac combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED₂₅ values for the combination ketorolac-B vitamins estimated from the isobolograms were 140.3 ± 15.1 and 80.4 ± 6.8 mg/kg for 100:100:1 and 100:100:5 proportions, respectively. These values were significantly higher than experimental ED₂₅ values which were 73.3 ± 6.3 and 47.7 ± 6.4 mg/kg for 100:100:1 and 100:100:5 proportions, respectively. Results indicate that oral ketorolac and B-vitamins can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of those combinations to relief this kind of pain in humans.