Sensory properties of unmyelinated sciatic nerve axons have previously been demonstrated by measuring stimulated release of calcitonin gene-related peptide in response to electrical, capsaicin, noxious heat and proton stimulation. However, it is unknown whether this responsiveness goes along with ectopic generation of action potential which may play a role in neuropathy. The isolated mouse skin-nerve preparation allows to record from characterized single-fibers and to compare sensory properties of the nerve endings in the receptive field (RF) with those of the axons in branches carrying the fiber under investigation. A total of 51 mechano-sensitive C-fibers were examined, 38 units were also heat-sensitive (CMH) and 8 sensitive to noxious cold (CMC). When the same stimuli were repeatedly applied to the axon, 2 CMC units responded to cold and 6 fibers to mechanical stimulation at von Frey threshold considerably higher than in the receptive fields. Most notably, 25 units (65%) showed axonal heat responses with thresholds and discharge rates in the same range as upon RF stimulation. These findings suggest that axons do express sensory transduction mechanisms similar to nociceptive nerve endings with respect to heat sensitivity, at least. Ectopic discharge would result from this sensitivity, if inflammatory sensitization to heat lowered heat thresholds to body temperature as it is the case in the skin. (spon. by EU-fp6)