Fig. 4. As a measure of the total thermal energy delivered to the tissue, the heat energy to elicit visual analogue scale (VAS) = 5 was calculated as the area under the curve (AUC) (temperature [°C]× time [s]) from start to end of the stimulation. Bars indicate mean ± SEM changes from baseline (30, 60, and 90 min after drug administration) in AUC. # Significant difference from placebo and CR665. White bar = placebo; black bar = oxycodone; hatched bar = CR665.