We think that our works will cause widespread interest to both experts and non-experts in this field. This is because numerous people suffer from tooth thermal pain in daily life and dentistry. However, we know little about the mechanism why cold stimulation evokes sharper and more shooting pain sensations in human teeth than hot stimulation. Although thermal pain sensation has been attributed to the activation of thermo-sensitive nociceptors (e.g., for skin tissue), it may not be exactly the case when tooth pain evoked by thermal stimulation is considered. It has been experimentally established that hot stimulation causes an inward flow (toward tooth pulp chamber) of dentinal fluid in dentinal microtubules whereas cold stimulation causes a reverse flow, and that intradental nociceptors (within dentinal microtubules) are not “equally sensitive” to mechanical activation (shear stress) by inward and outward dentinal fluid flows. To explain theoretically such different responses in intradental nociceptors, we proposed in this study the models that combine a computational fluid dynamics (CFD) model, which describes the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley (H-H) model, which describes the discharge behavior of intradental neurons. The simulation results agreed well with existing experimental measurements. The proposed models were further employed to provide mechanistic insights into the long-standing questions regarding the phenomenon that cold stimulation causes more rapid transient pain sensations than hot stimulation. The models developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to thermal stimulations used in dental practices.