Inflammatory pain has long been proposed to result from a lowering of the nociceptive heat threshold below tissue temperature. Bradykinin (BK) was shown to induce such a drastic sensitization to heat, and prostaglandins (e.g. PGE2) appear as the essential secondary mediators formed by cyclooxigenases 1 and 2 that are both expressed in fine cutaneous nerve fiber bundles. Surprisingly, also axons in peripheral nerve stems show highly differentiated noxious heat sensitivity, responding with action potential discharge much like their sensory terminals and releasing CGRP in a graded and calcium-dependent way. BK and PGE2 facilitate these axonal heat responses in wildtype but not TRPV1-/- mice, suggesting that TRPV1 could act as a generator of ectopic discharge and neurogenic inflammation in neuritis. However, neither in skin nor axons basal heat responsiveness depends on TRPV1 but is retained in the knockouts. This points to other heat-activated cation channels such as TRPV2, potentially forming TRP hetero-tetramers with distinct properties. TRPV2 appears to be functionally expressed in capsaicin- insensitive rat cultured sensory neurons of medium to large diameter, where it is strongly sensitized by intense noxious heat and cAMP analogs. A recently identified antagonist will help delineating TRPV2 functions in sensory terminals and searching for possible endogenous sensitizing compounds.