A Randomized Controlled Trial on the Effect of XXXX and @entity1286 on Conditioned Pain Modulation in Healthy Volunteers.

@entity1 @entity158 @entity1286 @entity20708 @entity1063 @entity1118
BACKGROUND: Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence @entity158 perception in @entity1 . Defects in descending @entity158 control are linked to @entity1118 states and its restoration may be a valuable analgesic tool. Conditioned @entity158 modulation (CPM) is a surrogate marker of descending inhibition that reduces the perception of @entity158 from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics @entity20708 , a combined mu-opioid receptor agonist and @entity1063 reuptake inhibitor, and @entity1286 , a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy @entity158 , to understand possible differences in mechanism of action between these opioids. METHODS AND RESULTS: On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of @entity20708 (100 mg immediate release tablet), @entity1286 (40 mg immediate release tablet) or placebo. At both time points, CPM was detectable after treatment with placebo and @entity20708 (peak @entity158 ratings reduced by 20-30% after application of the conditioning stimulus) but not after @entity1286 . Compared to placebo @entity1286 displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9%) at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2%) at 120-150 min after drug intake (p = 0.001). No difference in CPM between placebo and @entity20708 was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6%) at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9%) at 120-150 min after drug intake (p = 0.60). CONCLUSIONS: Our data show that in volunteers @entity1286 affects CPM, while @entity20708 was without effect despite identical experimental conditions. These data confirm that @entity20708 's main mechanism of action is distinct from that of @entity1286 and likely related to the effect of adrenergic stimulation on descending controls. TRIAL REGISTRATION: Netherlands Trial Register NTR2716.
