title: A double-blind, placebo-controlled study on the effect of buprenorphine and fentanyl on descending pain modulation: a human experimental study.
abstract: OBJECTIVE
  The descending pain inhibitory system is impaired in chronic pain and it is important to know how analgesics interact with this system. The aim of this human experimental pain, double-blind, randomized, placebo-controlled, 3 way cross-over study was to investigate the effect of 2 different opioids on descending pain inhibition using conditioning pain modulation (CPM) as a screening tool.
  
  
  METHODS
  Twenty-two healthy male volunteers were randomized to 72 hours of treatment with transdermal patches of fentanyl (25 μg/h), buprenorphine (20 μg/h), or placebo. The CPM was induced by immersing the hand into cold (3.0 ± 0.3°C) water and the evoked pain was continuously rated on a visual analogue scale (VAS). The test stimulus [pressure pain tolerance threshold (PPTol)] was applied to the contra-lateral arm. The CPM test was performed at baseline, 24, 48, and 72 hours after application of the patches.
  
  
  RESULTS
  The opioid treatments did not significantly (F=2.249; P=0.07) modulate the PPTol over the treatment period compared with placebo. The CPM-evoked PPTol increases (percentage increase from what was obtained at the baseline before patch application) were significantly enhanced by buprenorphine (P=0.004) and fentanyl (P=0.005) compared with placebo, with no differences between the 2 active drugs. Fentanyl significantly attenuated the time to cold water-evoked VAS peak compared with placebo (P=0.005), and the same trend was observed for buprenorphine (P=0.06). The VAS pain intensity was not affected.
  
  
  CONCLUSIONS
  The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers.
authors.affiliation: Center for Sensory-Motor Interaction, Department of Health Science and Technology, Aalborg University, Denmark. LAN@HST.AAU.DK
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Trine
authors.initials: T
authors.lastname: Andresen
authors.forename: Lasse P
authors.initials: LP
authors.lastname: Malver
authors.forename: Alexander
authors.initials: A
authors.lastname: Oksche
authors.forename: Heikki
authors.initials: H
authors.lastname: Mansikka
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002047:Buprenorphine / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005283:Fentanyl / Q000627:therapeutic use*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D005283:Fentanyl