title: Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine.
abstract: This is the first randomized controlled trial that tests the analgesic efficacy of transdermally delivered opioids in healthy volunteers and that assesses the sensitivity of different experimental pain tests to detect analgesia in this setting. Transdermal application of the full agonist fentanyl (TDF: 12.5 or 25 microg/h) and the partial agonist buprenorphine (TDB: 35 microg/h) was compared in three experimental models of acute pain (heat pain, painful electrical stimulation, cold pressor) in a double-blind, randomized, placebo-controlled, 4-arm crossover study with 20 healthy subjects (15 men, 5 women). Patches were administered for 72 h and pain levels measured at baseline and 24 and 72 h, with an 11-day wash-out. The cold pressor test was most sensitive to analgesic effects, with significant reductions in area under the pain intensity curve for all active compounds at 24 h (average reductions: 14% TDF 12.5 microg/h, 35% TDF 25 microg/h, 43% TDB 35 microg/h). There were significant increases in heat pain threshold for TDF 25 microg/h and TDB 35 microg/h. Painful electrical stimulation failed to demonstrate an analgesic effect. The magnitude of analgesia in the cold pressor model showed some correlation with TDF dosage and comparable effects for the full agonist fentanyl and the partial agonist buprenorphine. We conclude that the cold pressor test was most sensitive to analgesic effects in healthy subjects and that a transdermal dose of 12.5 microg/h fentanyl achieved significant pain reduction compared with placebo. Subjects experienced opioid-typical AEs including dizziness, nausea and vomiting. No serious AEs occurred.
authors.affiliation: Neural Plasticity Unit, Institute of Child Health, University College, London, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
authors.forename: Rolf
authors.initials: R
authors.lastname: Pokorny
authors.forename: Urs E
authors.initials: UE
authors.lastname: Gasser
authors.forename: Ute
authors.initials: U
authors.lastname: Richarz
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003080:Cold Temperature; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007101:Immersion; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods* / Q000592:standards*; D012680:Sensitivity and Specificity
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D005283:Fentanyl