The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.
Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc.
Departamento de Farmacobiología, Cinvestav-Sede Sur, C.P., 14330, Delegación Tlálpan, México D.F., México.
Janette Nallely
JN
Corona-Ramos
Área Académica de Farmacia del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, México.
Minarda
M
De la O-Arciniega
Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del IPN, C.P. 11340, México D.F., México.
Myrna
M
Déciga-Campos
Depto. de Sistemas Biológicos UAM-Xochimilco, C.P. 04960, México, D.F., México.
José Raúl
JR
Medina-López
Depto. de Sistemas Biológicos UAM-Xochimilco, C.P. 04960, México, D.F., México.
Adriana Miriam
AM
Domínguez-Ramírez
Departamento de Farmacobiología, Cinvestav-Sede Sur, C.P., 14330, Delegación Tlálpan, México D.F., México.
Osmar Antonio
OA
Jaramillo-Morales
Departamento de Farmacobiología, Cinvestav-Sede Sur, C.P., 14330, Delegación Tlálpan, México D.F., México.
Josué Vidal
JV
Espinosa-Juárez
Departamento de Farmacobiología, Cinvestav-Sede Sur, C.P., 14330, Delegación Tlálpan, México D.F., México.
Francisco Javier
FJ
López-Muñoz
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077206:Gabapentin; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D014147:Tramadol; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
combination; gabapentin; interaction; neuropathic pain; tramadol