Antinociceptive activity of the bradykinin B1 and B2 receptor antagonists, des-Arg9, [Leu8]-BK and HOE 140, in two models of persistent hyperalgesia in the rat.
There has been recent evidence linking bradykinin (BK) receptors with inflammation. This study has investigated the involvement of BK receptors in two models of persistent inflammatory hyperalgesia in rats. In a Freund's adjuvant-induced hyperalgesia model and an ultraviolet (UV)-induced hyperalgesia model in rats the specific B2 antagonist, D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-BK (HOE 140), was either ineffective or weakly active in reversing hyperalgesia. The specific B1 antagonist, des-Arg9, [Leu8]-BK, was effective in reversing or preventing the development of hyperalgesia in both Freund's adjuvant-induced hyperalgesia and UV-induced hyperalgesia. The B1 agonist, des-Arg9-BK, produced a small exacerbation of hyperalgesia in both models. Data suggest that in persistent inflammatory conditions in the rat bradykinin B1 receptors are involved in the accompanying hyperalgesia.
Sandoz Institute for Medical Research, Gower Place, London WC1E 6BN UK.
Martin Nicholas
MN
Perkins
Elizabeth
E
Campbell
Andy
A
Dray
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000528:radiation effects; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000145:classification / Q000187:drug effects; D014466:Ultraviolet Rays
D000700:Analgesics; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D005620:Freund's Adjuvant; D001920:Bradykinin