Antinociceptive synergy between dexamethasone and the B vitamin complex in a neuropathic pain model in the rat

The combination of dexamethasone and B-vitamins is widely used in México to treat neuropathic pain in human beings. However, so far there is no evidence in preclinical models about the efficacy of this combination. The purpose of this study was to assess the possible synergistic interaction between dexamethasone and the B-vitamin complex in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves in female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Dexamethasone (4-32 mg/kg), B-vitamins (75-600 mg/kg), or a combination of dexamethasone and B-vitamins (100:100:1 of vitamin B₁, B₆ and B₁₂, respectively) was administered subcutaneously and the antiallodynic effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between dexamethasone and B-vitamins (0.5:0.5). Dexamethasone (ED₃₀ 5.4 ± 1.2 mg/kg), B-vitamins (ED₃₀ 181.1 ± 2.6 mg/kg), and fixed-dose ratio dexamethasone-B-vitamins combinations dose-dependently reduced tactile allodynia in the rat. Theoretical ED₃₀ value for the combination estimated from the isobologram was 128.2 ± 5.8 mg/kg. This value was significantly higher than experimental ED₃₀ value which was 21.8 ± 2.3 mg/kg. Results indicate that subcutaneous administration of dexamethasone and B-vitamins interacted synergistically to reduce tactile allodynia in the rat and suggest the use of this combination to reduce neuropathic pain in humans.