Antinociceptive effects of combination of Tramadol and Acetaminophen on painful diabetic neuropathy in streptozotocin-induced diabetic rats†

ObjectiveThe purpose of this study was to establish the streptozotocin (STZ)-induced diabetic model with rats and investigate the antinociceptive effect of combination of Tramadol (TR) and Acetaminophen (NAPA) on the animal model for the first time.MethodsDiabetic model was induced by a single injection of STZ (60 mg/kg, intraperitoneal). Nociceptive thresholds were measured by means of electronic von Frey test, hot-plate test, and tail-flick test. On the 28th day of diabetes induction, diabetic rats with significant hyperalgesia were randomly divided into three groups: TR, NAPA, and TR-NAPA combination group. Each group was randomly divided into four subgroups. Three geometric series of drugs were given to each group respectively. Antinociceptive effects of the drugs were assessed at 15, 30, 60, 120, and 180 minutes after drug administration. 50% Maximum antinociceptive effect of each drug was determined by probit analysis, whereas interaction between TR and NAPA was evaluated by isobolographic analysis.ResultsHyperalgesia, along with hyperglycemia, developed 4 days after STZ injection and persisted at all tested time points until 28 days. TR, NAPA, and TR-NAPA combination administration all produced dose-dependent antinociceptive effects. Isobolographic analysis showed a significant deviation of TR/NAPA 50% maximum antinociceptive effect (in tail-flick test, but not in von Frey test) from the additive line.ConclusionsCombination of the two drugs produces an additive antinociceptive effect in tail-flick test, whereas probable additive antinociceptive effect in von Frey test in painful diabetic neuropathy rats.