TY - JOUR
T1 - Synergistic antiallodynic interaction of the metamizol-gabapentin combination
AU - Ortega-Varela, Luis F.
AU - Herrera, Jorge E.
AU - Caram-Salas, Nadia L.
AU - Rocha-Gonzalez, Hector I.
AU - Torres-López, Jorge E.
AU - Granados-Soto, Vinicio
PY - 2009/8
Y1 - 2009/8
N2 - 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 gabapentininduced 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.
AB - 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 gabapentininduced 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.
KW - Antiallodynia
KW - Gabapentin
KW - Isobologram
KW - Metamizol
KW - Spinal nerve ligation
KW - Synergy
UR - http://www.scopus.com/inward/record.url?scp=67650664302&partnerID=8YFLogxK
U2 - 10.1002/ddr.20315
DO - 10.1002/ddr.20315
M3 - Artículo
SN - 0272-4391
VL - 70
SP - 386
EP - 394
JO - Drug Development Research
JF - Drug Development Research
IS - 5
ER -