Synergistic antiallodynic interaction of the metamizol‐gabapentin combination

This study was designed to evaluate the possible antiallodynic interaction between metamizol and gabapentin in rats submitted to L5/L6 spinal nerve ligation. Metamizol, gabapentin, or a combination of both drugs were assessed after oral and intrathecal administration in neuropathic rats. Metamizol partially reduced tactile allodynia after intrathecal, but not oral, administration. Conversely, gabapentin reduced tactile allodynia in a dose‐dependent manner after both administration routes. Oral administration of a constant dose of metamizol (600 mg/kg) significantly increased the gabapentin‐induced antiallodynic effect. Moreover, the gabapentin ED₅₀ value was lower in the presence than in the absence of metamizol. Intrathecal co‐administration of metamizol and gabapentin in a dose‐fixed ratio (0.5:0.5) reduced tactile allodynia in rats. The theoretical ED₃₀ value for the spinal combination estimated from the isobologram was 118.4±12 µg, whereas that experimental ED₃₀ value was 66.2±10.1 µg indicating a synergistic interaction. Results indicate that metamizol, a cyclo‐oxygenase 2 inhibitor, is able to reduce tactile allodynia as well to increase the antiallodynic effect of gabapentin in the neuropathic rat. This combination could be useful to treat neuropathic pain in humans. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc.