title: Interaction of fentanyl and buprenorphine in an experimental model of pain and central sensitization in human volunteers.
abstract: OBJECTIVE
  : 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.
  
  
  CONCLUSIONS
  : For the doses administered in this study, buprenorphine and fentanyl showed an additive interaction.
authors.affiliation: Department of Anaesthesiology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tröster
authors.forename: Harald
authors.initials: H
authors.lastname: Ihmsen
authors.forename: Boris
authors.initials: B
authors.lastname: Singler
authors.forename: Jörg
authors.initials: J
authors.lastname: Filitz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koppert
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D002047:Buprenorphine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D004561:Transcutaneous Electric Nerve Stimulation / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D005283:Fentanyl