Effects of a combination of oral naproxen sodium and codeine on experimentally induced pain

The effect of an orally administered combination of naproxen sodium 550 mg and codeine phosphate 60 mg on threshold and tolerance to electrically induced pain, and on the threshold to thermally induced pain, was compared with the effects of naproxen sodium 550 mg alone, codeine phosphate 60 mg alone, and placebo. 16 female and 16 male, healthy young subjects, took part in four experiments on consecutive days of one week. On each day one treatment was administered, in random order, under double blind conditions. The combination increased threshold and tolerance to electrically induced pain and the threshold thermally induced pain markedly more than did naproxen sodium alone. Naproxen sodium plus codeine was also more effective in increasing threshold and tolerance to electrically induced pain than was codeine alone; the latter increased the threshold and tolerance to electrically induced pain and the threshold to thermally induced pain markedly more than placebo. Naproxen sodium alone had a relatively weak effect on the three pain measures. Reaction time to acoustic stimuli and the side effect profile were not significantly influenced by any of the treatments, and no severe adverse effects occurred. It is concluded that the combination of naproxen sodium 550 mg and codeine phosphate 60 mg, as indicated by its effects on experimentally induced pain, can produce more intense analgesia than the same doses of naproxen sodium and codeine administered alone, and that naproxen sodium and codeine phosphate given in combination enhanced each other's effect in an additive manner.