title: The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat.
abstract: 1. Interleukin-1 beta (IL-1 beta), IL-2 and IL-8 induced a mechanical hyperalgesia following intra-articular (i.artic.) injection into rat knee joints, whereas IL-6 and tumour necrosis factor alpha (TNF-alpha) were without effect. 2. Co-administration of IL-1 receptor antagonist (0.1 micrograms) with IL-1 beta (1 mu), IL-2 (10 mu) or IL-8 (0.1 mu) prevented the subsequent development of the hyperalgesia. 3. Co-administration of desArg9Leu8BK (0.5-5 nmol) with IL-1 beta (1 mu), IL-2 (10 mu) or IL-8 (0.1 mu) reduced the level of hyperalgesia at 1, 4 and 6 h post administration, whereas Hoe 140 (5 pmol) antagonized the hyperalgesia only at the 1 h time point. 4. Intravenous administration of desArg9Leu8BK (10 nmol kg-1) or Hoe 140 (100 pmol kg-1) following IL-1 beta (1 mu), IL-2 (10 mu), or IL-8 (0.1 mu) reversed the subsequent hyperalgesia. 5. Administration of desArg9BK into joints 24 h after pre-treatment with IL-1 beta (1 mu) produced analegsia at low doses (50 pmol) and hyperalgesia at a higher dose (0.5 nmol). Both these effects were blocked by desArg9Leu8BK (0.5 nmol). 6. Administration of desArg9BK (0.5 nmol i.artic.) to animals 24 h after pre-treatment with IL-2 (1-100 mu) or IL-8 (0.1-10 mu) had no effect on the load tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1, s.c.) prior to IL-1 beta (1 mu i.artic.) prevented the development of hyperalgesia. Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals 24 h after indomethacin and IL-1 beta pretreatment had no effect on the load tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1, s.c.) prior to IL-1beta (1 u i.artic.) prevented the development of hyperalgesia. Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals 24 h after indomethacin and IL-1 beta pretreatment had no effect on the load tolerated by the treated joint.8. These data suggest that both bradykinin B1 and B2 receptors are involved in the induction and maintenance of cytokine-induced hyperalgesia. They also show that the induction of B1 receptor-mediated hyperalgesia requires both cyclo-oxygenase products and IL-1 in vivo.
authors: Sandoz Institute for Medical Research, London.
authors: A J
authors: AJ
authors: Davis
authors: M N
authors: MN
authors: Perkins
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007270:Injections, Intra-Articular; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007719:Knee Joint; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000187:drug effects*
chemical_list: D016207:Cytokines; D007378:Interleukins; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D001920:Bradykinin; D007213:Indomethacin