Dose-dependent effects of morphine on experimentally induced cutaneous pain in healthy volunteers

This study examines the dose dependent analgesic effects of two doses of morphine and a single dose of alfentanil on experimentally induced cutaneous pain. In 16 healthy volunteers pain was induced by a skin burn injury and by continuous electrical skin stimulation. Mechanical pain thresholds (PT, von Frey filament), area of secondary hyperalgesia (SH) and 'wind-up like pain' upon repetitive stimulation (40-g load, 3 Hz, 30 s) were assessed. Analgesic effects on these pain parameters were tested at steady-state IV infusions of morphine, 50% (plasma concentration 15 ng/ml) and 100% (plasma concentration 30 ng/ml) of maximal tolerable dose to be given to healthy volunteers, and with an effective dose of alfentanil (plasma concentration 70 ng/ml). All effects were compared to active placebo, midazolam infusion (20 μg/kg for 10 min). Alfentanil significantly diminished the SH area in the burn injury model as well as in the electrical pain model. Additionally, alfentanil increased PT several fold in both models. The high dose of morphine showed a similar analgesic response pattern as alfentanil even though the effects were only statistically significant in the electrical pain model. The low dose of morphine as well as placebo did not affect these pain parameters. 'Wind-up like pain' was not influenced by any of the given drugs. In conclusion, the present study clearly indicates dose dependent effects of morphine on experimentally induced cutaneous pain. The high dose of morphine (30 ng/ml) was approximately equianalgesic to the administered alfentanil dose (70 ng/ml).