The race to the nociceptor: mechanical versus temperature effects in thermal pain of dental neurons

The sensing of hot and cold stimuli by dental neurons differs in several fundamental ways. These sen-sations have been characterized quantitatively through the measured time course of neural discharge signals that result from hot or cold stimuli applied to the teeth of animal mod-els. Although various hypotheses have been proposed to explain the underlying mechanism, the ability to test com-peting hypotheses against experimental recorded data using biophysical models has been hindered by limitations in our understanding of the specific ion channels involved in noci-ception of dental neurons. Here we apply recent advances in established biophysical models to test the competing hypotheses. We show that a sharp shooting pain sensa-tion experienced shortly following cold stimulation cannot be attributed to the activation of thermosensitive ion chan-nels, thereby falsifying the so-called neuronal hypothesis, which states that rapidly transduced sensations of coldness are related to thermosensitive ion channels. Our results sup-port a central role of mechanosensitive ion channels and the associated hydrodynamic hypothesis. In addition to the hydrodynamic hypothesis, we also demonstrate that the long time delay of dental neuron responses after hot stimula-tion could be attributed to the neuronal hypothesis—that a relatively long time is required for the temperature around nociceptors to reach some threshold. The results are useful as a model of how multiphysical phenomena can be combined to provide mechanistic insight into different mechanisms under-lying pain sensations.