To develop suitable pain management policies and drug delivery assist devices for analgesia (i. e., pain alleviation), it is necessary to have a mathematical model which captures the essential dynamics of this complex process. Recent work points to the fact that pain can be characterized by several dynamic stages, including anomalous diffusion and spatio-temporal dependency on tissue characteristics. This chapter presents a physiologically based mathematical framework to capture nociceptor pathways and pain reception, transmission and perception, in the human body. The main difference with previous studies is the explicit incorporation of fractional calculus tools as a natural way to characterize biological phenomena. Next, we observe the effects in skin impedance in the presence of nociceptor stimulation. For this purpose, a prototype device has been carefully designed to allow for the application of a noninvasive measurement protocol. Bio-electrical skin impedance captures the changes in tissue content at various time instants, sensor locations, and stimulus trains. The existence of a memory effect - or residual pain - is observed from the data.