The analgesic interaction of tramadol and morphine in rats: An isobolographic study

In order to assess possible synergistic antinociceptive interactions, the analgesic effects of intra-peritoneal tramadol and morphine administered either separately or in combination were determined using tail-flick latency test following exposure to radiant heat in rats. Groups of eight male Sprague-Dawley rats received either tramadol (3.90, 7.00, 12.50, and 22.20 mg kg^-1) and morphine (1.26, 2.25, 4.00 and 7.10 mg kg^-1) or a combination of tramadol and morphine (4 different combinations). The baseline latency was obtained before drug injection for each rat, then at 15, 30, 45, 60 and 75 min after injection. The effective dose (ED)₅₀ for either tramadol or morphine individually was 11.70 mgkg^-1 and 2.26 mg kg^-1, respectively. Based on isobolographic analysis, the ED₅₀ values obtained by drug combination were significantly less than the calculated additive values; which indicates that the co-administration of tramadol and morphine produces synergistic antinociception in the radiant heat tail-flick assay. Combination of morphine and tramadol administered intra-peritoneally can be used for the control of acute pain in rats.