INDUCTION OF B1 RECEPTORS IN-VIVO IN A MODEL OF PERSISTENT INFLAMMATORY MECHANICAL HYPERALGESIA IN THE RAT

The induction of mechanical hyperalgesia by B1 and B2 receptor agonists following an inflammatory insult has been studied in the rat. Intra-articular injection of bradykinin, but not desArg(9) bradykinin, into naive joints induced mechanical hyperalgesia with a reduction of up to 38% in load tolerated by the treated leg. Following intra-articular injection of Freund's complete adjuvant (FCA) the load tolerated by the treated leg was depressed for three days. The development of FCA-induced hyperalgesia was reduced by desArg(9)Leu(8)BK or Hoe 140. Bradykinin, desArg(9)BK and the metabolically stable B1 receptor agonist SarDPhe(8)desArg(9)BK were all hyperalgesic upon intra-articular administration 3 days after FCA administration. The hyperalgesia induced by desArg(9)BK and SarDPhe(8)desArg(9)BK was prevented by co-administration of desArg(9)Leu(8)BK but not by Hoe 140. At low doses (<10 nmol) bradykinin-induced hyperalgesia was presented by Hoe 140 but not by desArg(9)Leu(8)BK. At higher doses of bradykinin (>100 nmol) the hyperalgesia was reduced by both Hoe 140 and desArg(9)Leu(8)BK. These data suggest that following an inflammatory insult both bradykinin B1 and B2 receptor mechanisms are involved in the accompanying hyperalgesia.