The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury

• Published in: Drug development research Vol. 77; no. 5; pp. 217 - 226
• Main Authors: Corona-Ramos, Janette Nallely, De la O-Arciniega, Minarda, Déciga-Campos, Myrna, Medina-López, José Raúl, Domínguez-Ramírez, Adriana Miriam, Jaramillo-Morales, Osmar Antonio, Espinosa-Juárez, Josué Vidal, López-Muñoz, Francisco Javier
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2016; Wiley Subscription Services, Inc
• Subjects: Amines - administration & dosage; Amines - pharmacology; Analgesics - administration & dosage; Analgesics - pharmacology; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Animals; combination; Cyclohexanecarboxylic Acids - administration & dosage; Cyclohexanecarboxylic Acids - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; gabapentin; gamma-Aminobutyric Acid - administration & dosage; gamma-Aminobutyric Acid - pharmacology; interaction; Lethal Dose 50; Male; Mice; Neuralgia - drug therapy; Neuralgia - pathology; neuropathic pain; Rats; Rats, Wistar; tramadol; Tramadol - administration & dosage; Tramadol - pharmacology; interaction; tramadol; neuropathic pain; gabapentin; combination
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21313

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.