Recordings were made from small and medium diameter DRG neurons that expressed TRP proteins. Physiologically characterized skin nociceptors expressed either TRPV1 (type 2) or TRPV2 (type 4) in isolation. Other nociceptors co-expressed both TRP proteins and innervated deep tissue sites (gastrocnemius muscle, distal colon; type 5, type 8) and skin (type 8). Subpopulations of myelinated (type 4, type 8) and unmyelinated (type 5) nociceptors co-expressed both TRPs. Cells that expressed TRPV1 were excellent transducers of intense heat. Proportional inward currents were obtained from a threshold of ~46.5 up to ~ 56° C. In contrast, cells expressing TRPV2 alone (52° C threshold) did not reliably transduce the intensity of thermal events. Studies were undertaken to assess the capacity of skin and deep nociceptors to exhibit sensitization to repeated intense thermal stimuli (heat-heat sensitization; HHS). Only nociceptors that expressed TRPV2, alone or in combination with TRPV1, exhibited HHS. HHS was shown to be Ca⁺⁺ dependent in either case. Intracellular Ca⁺⁺ dependent pathways to HHS varied with the pattern of TRP protein expression. Cells co-expressing both TRPs modulated heat reactivity via serine/threonine phosphorylation or PLA₂ dependent pathways. Cells expressing only TRPV2 may have relied upon tyrosine kinases for HHS. We conclude that heat sensitization in deep and superficial, capsaicin sensitive and capsaicin insensitive C and A nociceptors, varies with the distribution of TRPV1 and TRPV2 proteins. The expression pattern of these proteins are specific to subclasses of physiologically identified C and A fiber nociceptors with highly restricted tissue targets.