Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat

Pain is unique among sensations in that the perceived intensity increases, or sensitizes, during exposure to a strong stimulus. One important mediator of sensitization is bradykinin (BK), a peptide released as a consequence o f tissue damage. BK enhances the membrane ionic current activated by heat i n nociceptive neurons, using a pathway that involves activation of protein kinase C (PKC). We find that five PKC isoforms are present in sensory neuro ns but that only PKC-epsilon is translocated to the cell membrane by BK. Th e heat response is sensitized when constitutively active PKC-epsilon is inc orporated into nociceptive neurons. Conversely, BK-induced sensitization is suppressed by a specific peptide inhibitor of PKC-epsilon. We conclude tha t PKC-epsilon is principally responsible for sensitization of the heat resp onse in nociceptors by bradykinin.