The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (520 mg/kg) and dexmedetomidine (5-20 mu g/kg) and three different combinations of tramadol+dexmedetomidine (5 + 5, 5 + 10 and 10+ 5, mg/kg+ mu g/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mu g/kg), dexmedetomidine (5 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol. or dexmedetomidine alone at several time points. In hot-plate test, tramadol + dexmedetomidine combination (5 + 10) exerted the strongest antinociceptive effect, while tramadol + dexmedetomidine combination (10 + 5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol + dexmedetomidine combination (5 + 5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 mu g/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5, 5 + 10 and 10 + 5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone. (C) 2007 Elsevier Inc. All rights reserved.