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The involvement of bradykinin B 1 and B 2 receptor mechanisms in cytokine‐induced mechanical hyperalgesia in the rat
Author(s) -
Davis A.J.,
Perkins M.N.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16174.x
Subject(s) - hyperalgesia , bradykinin , endocrinology , medicine , receptor antagonist , antagonist , pharmacology , cytokine , chemistry , receptor , nociception
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 desArg 9 Leu 8 BK (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 desArg 9 Leu 8 BK (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 desArg 9 BK 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 desArg 9 Leu 8 BK (0.5 nmol). 6 Administration of desArg 9 BK (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 desArg 9 BK (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 B 1 and B 2 receptors are involved in the induction and maintenance of cytokine‐induced hyperalgesia. They also show that the induction of B 1 receptor‐mediated hyperalgesia requires both cyclo‐oxygenase products and IL‐1 in vivo .