PROSTANOID-INDUCED POTENTIATION OF THE EXCITATORY AND SENSITIZING EFFECTS OF BRADYKININ ON ARTICULAR MECHANONOCICEPTORS IN THE RAT ANKLE JOINT

Responses of articular mechanonociceptors to intra-arterial injections of either bradykinin alone or in combination with prostaglandin E2, p rostaglandin I2 or the selective I-type prostaglandin receptor agonist cicaprost were investigated electrophysiologically in anaesthetized r ats. Bradykinin excited 76% of the mechanonociceptors studied and incr eased their responsiveness to repeated mechanical stimuli in 70% of un its. Tachyphylaxis of these responses was evident in all cases. Inject ions of minimally effective doses of prostaglandin I2 or cicaprost exc ited the mechanonociceptors and increased their responsiveness to mech anical stimuli. Injections of prostaglandin E2 evoked only small incre ases in spontaneous discharge. Potentiation of bradykinin-evoked excit ation was seen for combined injections of bradykinin with minimally ef fective or subthreshold doses of cicaprost in 86% of units, prostaglan din I2 in 40% of units and prostaglandin E2 in 56% of units. Combined injections of bradykinin and minimally effective or subthreshold doses of prostanoid agonist caused an increase in the responsiveness of mec hanonociceptors to mechanical stimuli greater than that caused by eith er drug alone in 80% of units for cicaprost, 80% for prostaglandin 2 a nd 100% for prostaglandin E2. The relative potencies of prostaglandin I2, cicaprost and prostaglandin E2, suggest that prostanoid-induced ex citation and sensitization of articular mechanonociceptors is mediated primarily by receptors for the naturally occurring prostanoid prostag landin I2 (I-type P-receptors). Prostaglandin E2 may be important in p otentiation of the sensitizing effects of bradykinin on mechanonocicep tor responsiveness.