A Double-blind, Placebo-controlled Study on the Effect of Buprenorphine and Fentanyl on Descending Pain Modulation: A Human Experimental Study : The Clinical Journal of Pain

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A Double-blind, Placebo-controlled Study on the Effect of Buprenorphine and Fentanyl on Descending Pain Modulation

A Human Experimental Study

Arendt-Nielsen, Lars PhD, Dr Med Sci*; Andresen, Trine PhD, MSc*,†; Malver, Lasse P. MD; Oksche, Alexander PhD, MD‡,§; Mansikka, Heikki PhD, MD; Drewes, Asbjørn M. PhD, Dr Med Sci, MD

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The Clinical Journal oF Pain 28(7):p 623-627, September 2012. | DOI: 10.1097/AJP.0b013e31823e15cb



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.


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.


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.


The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers.

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.

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