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

Objectives: 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 mu g/h), buprenorphine (20 mu g/h), or placebo. The CPM was induced by immersing the hand into cold (3.0 +/- 0.3 degrees 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. Discussion: The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers.