Stimulus properties and antinociceptive effects of selective bradykinin B1 and B2 receptor antagonists in rats

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Abstract
Research has documented the differential role of bradykinin (BK) B1 and B2 receptors in the mediation of inflammatory nociception and this research suggests that selective B1 antagonists may have therapeutic potential against chronic inflammatory pain. The present study sought to further define the stimulus properties (reinforcing and aversive effects) of the selective B1 antagonist des-Arg9,(Leu8)-BK (0.0, 0.03, 0.1, and 0.3 mg/kg) and the selective B2 antagonist HOE 140 (0.0, 0.1, 0.5, and 1.0 mumol/kg) in the Freund's adjuvant (100 microliters, i.p.) model of chronic inflammatory nociception using the place preference paradigm. In addition, this research examined the differential antinociceptive effects of these antagonists on the formalin test (2.5%). Des-Arg9,(Leu8)-BK exhibited antinociceptive effects against both the first and second phases of the formalin response; HOE 140 tended to increase nociceptive responding on both phases of the formalin response. In the place preference paradigm, des-Arg9,(Leu8)-BK, but not HOE 140, exhibited negatively reinforcing effects (i.e. analgesia) in adjuvant-inflamed animals and aversive effects in noninflamed control animals. Neither compound exhibited positively reinforcing effects (i.e. abuse potential). These results further define the stimulus properties of these selective BK antagonists and provide additional evidence to support the notion that B1 antagonists may possess therapeutic potential for conditions of chronic inflammatory pain.