Effect of bradykinin receptor antagonists on vincristine- and streptozotocin-induced hyperalgesia in a rat model of chemotherapy-induced and diabetic neuropathy.

The role of bradykinin receptor blockade in the development of neuropathies caused by diabetes mellitus and vincristine was examined. The effects of a potent and selective B(1) receptor antagonist (des-Arg(10)-HOE 140) as well as a specific antagonist of B(2) receptors (HOE 140) were investigated. Both agents significantly decreased hyperalgesia caused otherwise by vincristine. In a diabetic neuropathy model, both agents almost completely suppressed hyperalgesia in the first 10 days of the study. However, from day 11 after administration of streptozotocin, the action of des-Arg(10)-HOE 140 was significantly weaker than that of HOE 140. The results of the study suggest involvement of both B(1) and B(2) receptors in transmission of nociceptive stimuli in the vincristine-induced as well as diabetic neuropathy model.