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

Abstract

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.

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

“…This is exemplified by the findings in the cold pressor model. Pain in the cold pressor model is often assessed by the area under the VAS curve and accordingly opioid analgesia can be shown for most opioids [8,58,81,107,125].…”

“…Codeine (Table 6) Acute models Skin: Codeine worked against acute experimental pain to heat, pressure, single/repeated electrically stimulation and in the cold pressor test [100,[105][106][107][108].Two studies applied Table 6 Schematic overview of studies involving codeine in human experimental pain models In the column 'model' the method for pain assessment is normal font, and the method for pain induction is bolded. Abbreviations: pain detection threshold (PDT), pain tolerance threshold (PTT), area under curve (AUC), visual analogue scale score (VAS), hyperalgesia (HA).…”

Effects of graded oral doses of a new 5‐hydroxytryptamine/noradrenaline uptake inhibitor (Ro 15‐8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in healthy men.

“…Electrical stimulation Chains of square wave constant current impulses of 1 ms duration and a pulse frequency of 100 s-1 were used to induce pain (Lahoda et al, 1977;Stacher et al, 1979Stacher et al, , 1982Stacher et al, , 1983Stacher et al, , 1986. The stimuli were administered by means of a pair of silver ball electrodes attached to the earlobule of the subjects' nondominant side.…”

“…The intervals between the chains ranged randomly from 15 to 25 s. Pain threshold and pain tolerance values were stored on-line by a computer on magnetic disc. Thermal stimulation Radiant heat of a constant intensity was used to induce pain (Stacher et al, 1982(Stacher et al, , 1983(Stacher et al, , 1986. On the volar surface of the subjects' dominant forearm, eight spots were marked and numbered from one to eight.…”

“…Ro 15-8081 is rapidly absorbed from the gastrointestinal tract and doses of up to 30 mg kg-1 day-1 were systematically well tolerated by dogs during a 4-week oral toxicity study (HoffmannLa Roche, 1986). The present investigation was aimed at assessing, in healthy man, the analgesic activity of Ro 15-8081 using two models with electrically and thermally induced cutaneous pain, which previously have been shown to discriminate reliably between the effects of opioid (Stacher et al, 1979(Stacher et al, , 1982(Stacher et al, , 1983(Stacher et al, , 1986 as well as of antipyretic-antiinflammatory analgesics (Stacher et al, 1986) and placebo. In addition, the study assessed the compound's effects on psychomotor function, subjective feelings and side effect profile.…”