Bradykinin B1 and B2 receptors, tumour necrosis factor α and inflammatory hyperalgesia

1 The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the endpoint of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). 2 DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. 3 Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. 4 DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. 5 A small dose of DABK+a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. 6 Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. 7 The hyperalgesic response to LPS (1 mu g) was inhibited by DALBK or HOE 140 and abolished by DALBK;HOE 140. The hyperalgesic response to LPS (5 mu g) was not antagonized by DALBK + HOE 140. 8 These data suggest: (a) a predominant role for B-2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B-1 and B-2 receptors if the hyperalgesic stimulus is of sufficient magnitude.