STIMULUS PROPERTIES AND ANTINOCICEPTIVE EFFECTS OF SELECTIVE BRADYKININ B-1 AND B-2 RECEPTOR ANTAGONISTS IN RATS

Research has documented the differential role of bradykinin (BK) B-1 a nd B-2 receptors in the mediation of inflammatory nociception and this research suggests that selective B-1 antagonists may have therapeutic potential against chronic inflammatory pain. The present study sought to further define the stimulus properties (reinforcing and aversive e ffects) of the selective B-1 antagonist des-Arg(9),(Leu(8))-BK (0.0, 0 .03, 0.1,and 0.3 mg/kg) and the selective B-2 antagonist HOE 140 (0.0, 0.1, 0.5, and 1.0 mu mol/kg) in the Freund's adjuvant (100 mu l, i.p. ) model of chronic inflammatory nociception using the place preference paradigm. In addition, this research examined the differential antino ciceptive effects of these antagonists on the formalin test (2.5%). De s-Arg(9),(Leu(8))-BK exhibited antinociceptive effects against both th e first and second phases of the formalin response; HOE 140 tended to increase nociceptive responding on both phases of the formalin respons e. In the place preference paradigm, des-Arg(9),(Leu(8))-BK, but not H OE 140, exhibited negatively reinforcing effects (i.e. analgesia) in a djuvant-inflamed animals and aversive effects in noninflamed control a nimals. Neither compound exhibited positively reinforcing effects (i.e . abuse potential). These results further define the stimulus properti es of these selective BR antagonists and provide additional evidence t o support the notion that B-1 antagonists may possess therapeutic pote ntial for conditions of chronic inflammatory pain.