Malfunctioning of the ascending nociceptive pathway plays a key role in the development of chronic pain, e.g. central sensitization. In psychophysical experiments, subject's binary responses are measured during applying electrocutaneous stimulation. The stimulation delivers a square waveform parameterized by three temporal parameters, number of pulses (NoP), inter-pulse interval (IPI), pulse width (PW), and amplitude of the current (IA). These are the input-output measurements of this pathway accounting for peripheral activation, firing rate, synaptic transfer and supraspinal activation (Figure 1A). The relevant neurophysiological parameters may reflect the state of nociceptive system. To provide sufficient information to get the values of these parameters, multiple combinations of the settings in stimulus parameters are required. The challenge is to develop a reliable algorithm to estimate the parameters and to find an optimal stimulus setting.