Central B2 receptor involvement in the antinociceptive effect of bradykinin in rats.

1. The effect of intracerebroventricular (i.c.v.) injection of bradykinin (BK) and related peptides was tested on the dental pulp electrical stimulation threshold (DPEST) in rats. 2. BK (4, 8 and 16 nmol) induced a dose-dependent increase of DPEST, indicative of an antinociceptive effect. 3. I.c.v. injection of equimolar doses of BK-related peptides, Lys-BK and Met-Lys-BK, also induced an increase of DPEST, but the magnitude of the effect was not as intensive as that induced by BK, when the maximum increase of DPEST was considered. The peptide T-kinin induced a short lasting and weak antinociceptive effect. 4. The B1 agonist, des-Arg9-BK (8 nmol) induced a significant antinociceptive effect, but this was not as intensive as that induced by BK. 5. The B2 antagonist D-Arg0-Hyp3-Thi5,8-D-Phe7-BK (D-Arg0) competitively antagonized the BK-induced antinociception. Likewise, Hyp3-Thi5,8-D-Phe7-BK (Hyp) also antagonized BK effect. However, the compound Thi5,8-D-Phe7-BK (Thi), initially considered a pure BK antagonist, induced an antinociceptive effect, supporting previous observations that this peptide can also act as a partial agonist. 6. It is concluded that the dose-dependent antinociceptive effect induced by i.c.v. injection of BK is mediated by the stimulation of brain B2 receptors.