| Abstract: | 1. This study was designed to investigate the role of bradykinin (BK), as well as the subtype of BK receptors involved, in formalin-induced hindpaw pain in the mouse by use of selective B1 and B2 receptor antagonists. In addition, we have analysed whether or not BK may be involved in formalin-induced hindpaw oedema in the mouse. 2. The pretreatment of animals with captopril (2 and 5 mg kg-1, s.c.) significantly increase the first and the second phases of formalin-induced pain. 3. Co-injection of the selective B1 receptor antagonist des-Arg9Leu8]-BK (0.2-0.4 nmol/paw), together with formalin, caused graded and similar inhibitions of both phases of formalin-induced pain. Similar results were obtained with the B2 antagonists NPC 349 (D-ArgHyp3,Thi5,8-D-Phe7]-BK) and NPC 567 (D-ArgHyp3, D-Phe7]-BK) (0.2 and 0.6 nmol/paw). Higher concentrations of these antagonists (1 nmol/paw) failed to antagonize formalin-induced pain. 4. The new potent and selective B2 receptor antagonists, Hoe 140 (D-ArgHyp3,Thi5,D-Tic7,Oic8]-BK), NPC 17731 (D-ArgHyp3, trans-4-propoxy-D-proline (transpropyl)7, Oic8]-BK), and NPC 17761 (D-ArgHyp3, trans-4-propoxy-D-proline (trans thiophenyl)7, Oic8]-BK) (0.02 to 1.0 nmol/paw), also caused significant inhibitions of both phases of formalin-induced pain. When Hoe 140 was injected subcutaneously 30 min before formalin injection (9.9 and 99 nmol kg-1), it significantly attenuated both phases of formalin-induced pain.(ABSTRACT TRUNCATED AT 250 WORDS) |
