Prostanoid-induced potentiation of the excitatory and sensitizing effects of bradykinin on articular mechanonociceptors in the rat ankle joint

Abstract

Responses of articular mechanonociceptors to intra-arterial injections of either bradykinin alone or in combination with prostaglandin E2, prostaglandin I2 or the selective I-type prostaglandin receptor agonist cicaprost were investigated electrophysiologically in anaesthetized rats. Bradykinin excited 76% of the mechanonociceptors studied and increased their responsiveness to repeated mechanical stimuli in 70% of units. Tachyphylaxis of these responses was evident in all cases. Injections of minimally effective doses of prostaglandin I2 or cicaprost excited the mechanonociceptors and increased their responsiveness to mechanical stimuli. Injections of prostaglandin E2 evoked only small increases in spontaneous discharge. Potentiation of bradykinin-evoked excitation was seen for combined injections of bradykinin with minimally effective or subthreshold doses of cicaprost in 86% of units, prostaglandin 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 mechanonociceptors to mechanical stimuli greater than that caused by either drug alone in 80% of units for cicaprost, 80% for prostaglandin I2 and 100% for prostaglandin E2. The relative potencies of prostaglandin I2, cicaprost and prostaglandin E2, suggest that prostanoid-induced excitation and sensitization of articular mechanonociceptors is mediated primarily by receptors for the naturally occurring prostanoid prostaglandin I2 (I-type P-receptors). Prostaglandin E2 may be important in potentiation of the sensitizing effects of bradykinin on mechanonociceptor responsiveness.