A NOVEL HEAT-ACTIVATED CURRENT IN NOCICEPTIVE NEURONS AND ITS SENSITIZATION BY BRADYKININ

Pain differs from other sensations in many respects. Primary pain-sens itive neurons respond to a wide variety of noxious stimuli, in contras t to the relatively specific responses characteristic of other sensory systems, and the response is often observed to sensitize on repeated presentation of a painful stimulus, while adaptation is typically obse rved in other sensory systems. In most cases the cellular mechanisms o f transduction and sensitization in response to painful stimuli are no t understood. We report here that application of pulses of noxious hea t to a subpopulation of Isolated primary sensory neurons rapidly activ ates an inward current. The ion channel activated by heat discriminate s poorly among alkali cations. Calcium ions both carry current and par tially suppress the current carried by other tons. The current is mark edly increased by bradykinin, a potent algogenic nonapeptide that is k nown to be released in vivo by tissue damage. Phosphatase inhibitors p rolong the sensitization caused by bradykinin, and a similar sensitiza tion is caused by activators of protein kinase C. We conclude that bra dykinin sensitizes the response to heat by activating protein kinase C .