1 The effects of BK agonists and antagonists, and other hyperalgesic/antihy
peralgesic 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 tr
emor).
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 onl
y 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 1
40 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
.