Induction of bradykinin B1 receptors in vivo in a model of ultra‐violet irradiation‐induced thermal hyperalgesia in the rat

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Abstract
1 The role of bradykinin B1 receptors in the thermal hyperalgesia following unilateral ultra-violet (u.v.) irradiation of the hindpaw of rats has been investigated. 2 In non-irradiated (naive) animals the B1 receptor agonist des-Arg9-bradykinin and bradykinin (BK) (up to 1 μmol kg−1 i.v.) had no effect on withdrawal latency to a noxious heat stimulus when administered 60 min before testing. 3 Following exposure of one hindpaw to strong u.v. irradiation the withdrawal latency of the u.v.-treated paw to radiant noxious heat fell by a maximum of 50% after 48 h. There was no reduction in latency in the contralateral paw. 4 des-Arg9-BK (1–100 nmol kg−1 i.v.) administered 24 h after u.v. exposure caused a further dose-dependent fall (50 ± 4% reduction from saline injected animals at 100 nmol kg−1 i.v.) in withdrawal latency in the u.v.-treated paw when measured 60 min after injection. The withdrawal latency of the contralateral paw was also reduced but to a lesser extent following des-Arg9-BK (100 nmol kg−1 i.v.) with a maximum reduction of 19 ± 3%. 5 Bradykinin also induced a further reduction in withdrawal latency (33 ± 5% reduction at 1 μmol kg−1) although it was not as effective as des-Arg9-BK. Bradykinin did not reduce the withdrawal latency in the contralateral paw. 6 The hyperalgesic action of both des-Arg9-BK (10 nmol kg−1 i.v.) and bradykinin (100 nmol kg−1 i.v.) were antagonized by the B1 receptor antagonist, des-Arg9,Leu8-BK (200 nmol kg−1 i.v.) but not by the B2 receptor antagonist, HOE 140 (0.5 μmol kg−1 i.v.). 7 The results suggest that in conditions of inflammatory hyperalgesia bradykinin B1 receptors are induced both locally and distant to the inflamed area, activation of which leads to further thermal hyperalgesia. In addition, in these conditions bradykinin appears to act predominantly via B1 receptors, presumably after degradation to des-Arg9-BK.