Antagonism of the algesic action of bradykinin on the human blister base.

The effect of bradykinin (BK) and some analogues of BK on the human blister base was studied. BK produced reproducible dose-related increases in pain responses. A characteristic delay, which was not dose-related occurred between application of BK and the resultant response. The rank order of potency of several kinin analogues on the pain response was BK much much greater than sigma-cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin greater than des-Arg9-BK. No increase in pain response was seen with repeated application of the selective B1-receptor agonist des-Arg9-BK to the same blister base at 4h intervals. The B1 receptor antagonist des-Arg9-Leu8-BK was without effect against BK-induced responses. The B2-receptor antagonists, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-TFA and D-Pro-Phe-Arg-heptylamide produced significant antagonism of the bradykinin-induced pain responses at doses which had no effect against 5-hydroxytryptamine or potassium chloride. It is concluded that the kinin receptor mediating pain on the human blister base is of the B2 type.