This paper discusses some of the practical limitations and issues, which exist for the input-output (IO) slope curve estimation (SCE) in neural, brain and spinal, stimulation techniques. The drawbacks of the SCE techniques by using existing uniform sampling and Fisher-information-based optimal IO curve estimation (FO-IOCE) methods are elaborated. A novel IO SCE technique is proposed with a modified sampling strategy and stopping rule which improve the SCE performance compared to these methods. The effectiveness of the proposed IO SCE is tested on 1000 simulation runs in transcranial magnetic stimulation (TMS), with a realistic model of motor evoked potentials. The results show that the proposed IO SCE method successfully satisfies the stopping rule, before reaching the maximum number of TMS pulses in 79.5% of runs, while the estimation based on the uniform sampling technique never converges and satisfies the stopping rule. At the time of successful termination, the proposed IO SCE method decreases the 95th percentile (mean value in the parentheses) of the absolute relative estimation errors (AREs) of the slope curve parameters up to 7.45% (2.2%), with only 18 additional pulses on average compared to that of the FO-IOCE technique. It also decreases the 95th percentile (mean value in the parentheses) of the AREs of the IO slope curve parameters up to 59.33% (16.71%), compared to that of the uniform sampling method. The proposed IO SCE also identifies the peak slope with higher accuracy, with the 95th percentile (mean value in the parentheses) of AREs reduced by up to 9.96% (2.01%) compared to that of the FO-IOCE method, and by up to 46.29% (13.13%) compared to that of the uniform sampling method.