Background: Several experimental pain models have been used to measure opio
id effects in humans. The aim of the current study was to compare the quali
ties of five frequently used experimental pain tests to measure opioid effe
cts.
Methods: The increase of electrical, heat, and pressure pain tolerance and
the decrease of ice-water and ischemic pain perception was determined at ba
seline and at four different plasma concentrations of alfentanil (n = 7) ad
ministered as target controlled infusion or placebo (n = 7). A linear mixed
-effects modeling (NONMEM) was performed to detect drug, placebo, and time
effect as well as interindividual and intraindividual variation of effect.
Results: Only the electrical, ice-water, and pressure pain tests are sensit
ive to assess a concentration-response curve of alfentanil. At a plasma alf
entanil concentration of 100 ng/ml, the increase in pain tolerance compared
with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and
21.7% for Ice-water pain. The slope of the linear concentration-response cu
rve had an interindividual coefficient of variation of 58.3% in electrical
pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual err
or including intraindividual variation at an alfentanil concentration of 10
0 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% fo
r ice-water pain. Electrical pain was affected by a significant placebo eff
ect, and pressure pain was affected by a significant time effect.
Conclusion: Electrical, pressure, and ice-water pain, but not ischemic and
heat pain, provide significant concentration-response curves in the clinica
lly relevant range of 200 ng/ml alfentanil or lower. The power to detect a
clinically relevant shift of the curve is similar in the three tests. The a
ppropriate test(s) for pharmacodynamic studies should be chosen according t
o the investigated drug(s) and the study design.