Effect of cebranopadol on pain responses: pain threshold (open circles) and pain tolerance (closed circles). Best, median, and worst fits (as determined by R²) are given (threshold and tolerance were fitted simultaneously), together with the corresponding pharmacokinetic data fits. The solid and broken lines are the data fits for pain threshold and tolerance, respectively. (A, D) Best pharmacodynamic (PD) fit, subject 4; (B, E) median PD fit, subject 12; (C, F) worst PD fit, subject 11.