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, 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.