Bradykinin-induced knee joint incapacitation involves bradykinin B2 receptor mediated hyperalgesia and bradykinin B1 receptor-mediated nociception.
The participation of B1 and B2 types of bradykinin receptors was studied in the rat knee-joint incapacitation test. Five intra-articular successive hourly administrations of bradykinin produced progressive incapacitation, thus indicating that bradykinin induced sensitization to its own nociceptive effect. Four co-injections of bradykinin with the bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin were without nociceptive effect. However, a 5th injection of bradykinin alone produced intense incapacitation. The bradykinin B2 receptor antagonist HOE-140 ([D-Arg)[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), or indomethacin, prevented the bradykinin-induced incapacitation. However, successive co-injections of bradykinin with prostaglandin E2, in contrast to bradykinin alone, did induce incapacitation in animals pretreated with indomethacin or HOE-140. The injection of the bradykinin B1 receptor agonist des-Arg9-bradykinin into prostaglandin E2-treated joints did induce incapacitation, although administration of the bradykinin B1 receptor agonist or prostaglandin E2 alone did not induce incapacitation. In conclusion, in ongoing articular inflammation, it is suggested that the bradykinin B1 receptor is particularly involved with nociceptor activation, while the bradykinin B2 receptor is related to nociceptor sensitization.
Tonussi
C R
CR
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Ferreira
S H
SH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D065168:Bradykinin Receptor Antagonists; D015232:Dinoprostone / Q000494:pharmacology; D006614:Hindlimb / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D007596:Joints / Q000473:pathology; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin