Bradykinin B1 and B2 receptor mechanisms and cytokine-induced hyperalgesia in the rat.
The involvement of bradykinin (BK) B1 and B2 receptors in cytokine-induced hyperalgesia has been studied in the rat. Intraplantar injections of interleukin (IL) 1 beta and tumor necrosis factor alpha (TNF alpha) induced thermal hyperalgesia, with in the the case of IL-1 beta, contralateral hyperalgesia also present. Subsequent to administration of IL-1 beta, but not after TNF alpha, des-Arg9-BK reduced the withdrawal latency in both ipsi- and contra-lateral paws. Mechanical hyperalgesia was also induced by IL-1 beta, IL-2, and IL-8 when injected into rat knee joints, whereas IL-6 and TNF alpha were without effect. Coadministration of des-Arg9,Leu8-BK prevented the development of the cytokine-induced hyperalgesia for the duration of the experiment (6 h), but HOE-140 only reversed the hyperalgesia for the 1st h. At 3.5 h after IL-1 beta, IL-2, or IL-8, administration of des-Arg9,Leu8-BK or HOE-140 (iv) completely reversed the hyperalgesia. Twenty-four hours after pretreatment with IL-1 beta, injection of des-Arg9-BK into the joint produced opposite effects, depending on the dose: at 50 pmol the hyperalgesia was reversed, but at 0.5 nmol there was further hyperalgesia. Both responses were blocked by B1 but not B2 receptor antagonists. These data suggest that both B1 and B2 receptors are involved in the induction and maintenance of cytokine-induced hyperalgesia. B1 receptors appear to play a more important role than B2 receptors in the development of mechanical hyperalgesia.
Perkins
M N
MN
Sandoz Institute for Medical Research, London, United Kingdom.
Kelly
D
D
Davis
A J
AJ
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006930:Hyperalgesia / Q000209:etiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha