Enhanced analgesic effects of propacetamol and tramadol combination in rats and mice

Drug combinations have more potential advantage of greater analgesia than monotherapy. By the combination of analgesics with different mechanism, potency of analgesia can be maximized while the incidence of adverse effects is minimized. This study was aimed to assess a possible interaction in the antinociceptive effects between tramadol (T) and propacetamol (P) when administered in combination against nociceptive effects induced by physical or chemical injury in mice and rats. Three series of experiments were performed. The first was to determine effects of P and T alone or in combination in the acetic acid (AA)-induced writhing test in mice. Combination of T/P (3.9/67.5, 7.8/135, 15.6/271 mg/kg, intraperitoneally (i.p.)) elicited dose-dependent antinociception. The second determined whether the antinociceptive effects of the drugs observed in a test of persistent chemical pain could be seen in a test of acute thermal pain and the back-paw licking response was tested on the hot plate. The back-paw licking latency at different times after drugs obtained with the combination (16/270, 32/540 mg/kg, i.p. T/P) was longer than the respective values obtained with the individual agents. The third was designed to compare the antinociceptive effects between the drugs, either alone or in combination in the rat tail-flicks test. Combination of T/P (5.5/96, 11/192 mg/kg i.p.) both showed effects of higher potency than T and P, respectively. The data obtained confirmed that propacetamol is able to enhance the antinociceptive activity of tramadol.