Synergistic interaction between gabapentin and metamizol in the rat formalin test

The purpose of this study was to assess the possible synergistic interaction between gabapentin and metamizol 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%). Formalin injection induced a typical flinching behavior indicating nociception. Reduction of the number of flinches was considered as antinociception. Gabapentin (10-300 mg/kg), metamizol (30-600 mg/kg), or the combination of gabapentin and metamizol were administered orally and the antinociceptive effect in the formalin test was determined, Isobolographic analyses were used to define the nature of the functional interaction between gabapentin and metamizol in a fixed-dose ratio (0.5:0.5). Gabapentin (ED₃₀ 18.3 ± 7.9 mg/kg), metamizol (ED₃₀ 139.2 ± 6.2 mg/kg) and fixed-dose ratio gabapentin-metamizol combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED₃₀ value for the combination estimated from the isobologram was 78.8 ± 5.5 mg/kg, whereas that experimental ED ₃₀ value was 15.0 ± 1.2 mg/kg. Results indicate that oral administration of gabapentin and metamizol can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of this combination to relieve pain in humans.