The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine‐induced mechanical hyperalgesia in the rat

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Abstract
1 Interleukin-1β (IL-1β), 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 α (TNF-α) were without effect. 2 Co-administration of IL-1 receptor antagonist (0.1 μg) with IL-1β (1 u), IL-2 (10 u) or IL-8 (0.1 u) prevented the subsequent development of the hyperalgesia. 3 Co-administration of desArg9Leu8BK (0.5–5 nmol) with IL-1β (1 u), IL-2 (10 u) or IL-8 (0.1 u) reduced the level of hyperalgesia at 1, 4 and 6h 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-1β (1 u), IL-2 (10 u), or IL-8 (0.1 u) reversed the subsequent hyperalgesia. 5 Administration of desArg9BK into joints 24 h after pre-treatment with IL-1β (1 u) produced analgesia 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 u) or IL-8 (0.1–10 u) had no effect on the load tolerated by the treated joint. 7 Administration of indomethacin (1 mg kg−1, s.c.) prior to IL-1β (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-1β 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.

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