Interaction of Fentanyl and Buprenorphine in an Experimental Model of Pain and Central Sensitization in Human Volunteers

OBJECTIVES: : There is controversy about combining opioids with different receptor affinities. We assessed the analgesic and antihyperalgesic effects of the μ-agonist fentanyl and the partial μ-agonist/κ-antagonist buprenorphine in a human pain model, when given alone or in combination. METHODS: : Fifteen healthy male volunteers (22 to 35 y) were included in this randomized, double-blind, placebo-controlled, cross-over study. Transcutaneous electrical stimulation induced spontaneous acute pain and stable areas of secondary hyperalgesia. Pain intensities, measured on a numeric rating scale from 0 to 10, and the size of the hyperalgesic areas were assessed before, during, and after an intravenous infusion of 1.5 µg/kg fentanyl, 1.5 µg/kg buprenorphine, a combination of 0.75 µg/kg fentanyl and buprenorphine each, or saline 0.9%. Maximum effects of the treatments were compared by repeated measurement analysis of variance, and pharmacodynamic interaction models were fitted to the data. RESULTS: : Starting from a baseline value of numeric rating scale=6, the maximum reduction of pain intensity after correction for placebo effects was 43.9 ± 22.2% after fentanyl, 35.0 ± 23.0% after buprenorphine, and 39.4 ± 20.8% after the combination (mean ± SD, P=0.24). The maximum reduction of the hyperalgesic area was 38.3 ± 39.0% for fentanyl, 34.4 ± 32.7% for buprenorphine, and 30.0 ± 53.8% for the combination (mean ± SD, P=0.82). The time courses were best described by pharmacodynamic models assuming an additive interaction. DISCUSSION: : For the doses administered in this study, buprenorphine and fentanyl showed an additive interaction.