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 microl of diluted formalin (1%). Reduction of 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 (ED25 157.3+/-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.