B vitamins increase the analgesic effect of diclofenac in the rat

The purpose of this study was to assess the possible synergistic interaction between diclofenac and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) 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 the number of flinches was considered as antinociception. Diclofenac (0.31-316 mg/kg), B-vitamins (32-178 mg/kg), or a combination of B-vitamins and diclofenac 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 diclofenac in two proportions (1:1, 1:3; Diclofenac:B-Vitamins). Diclofenac (ED30 3.7+/-0.4 mg/kg), B-vitamins (ED30 76.2+/-8.5 mg/kg), and fixed-ratio B-vitamins-diclofenac combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED30 values for the combination estimated from the isobolograms were 39.9+/-4.2 and 58.1+/-6.4 mg/kg for 1:1 and 1:3 proportions, respectively. These values were significantly higher than experimental ED30 values which were 7.4+/-9.3 and 22.8+/-9.8 mg/kg for 1:1 and 1:3 proportions, respectively. Results indicate that oral diclofenac 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.