Ion channels that transduce heat (A), cold (B), and mechanical stimuli (C) are depicted. Stimuli are presented to the skin, which is depicted as containing representative nonneuronal cells (such as keratinocytes) (brown cells) and the free nerve endings of nociceptor axons (blue). Arrows next to channels indicate whether their activity is increased or decreased upon stimulation. Note that these nocisensors are not necessarily coexpressed in the same terminal. The curved arrow in C refers to the transducer(s) and other channels and molecules that contribute to the firing pattern (e.g., rapidly adapting vs. slowly adapting) in these fibers. Molecularly unidentified channels with indicated ion permeabilities inside drawing of channel are referred to as “putative RA MA channel” and “putative IA/SA MA channel.” MA, mechanically activated; RA, rapidly adapting; IA, intermediate adapting; SA, slowly adapting.