THE MODULATORY EFFECTS OF BRADYKININ B-1 AND B-2 RECEPTOR ANTAGONISTSUPON VISCERO-VISCERAL HYPER-REFLEXIA IN A RAT MODEL OF VISCERAL HYPERALGESIA

This study assessed the relative involvement of the two bradykinin (Bk ) receptors !Bi and BZ) in the viscero-visceral hyper-reflexia (VVH) a nd plasma extravasation observed in an animal model of cystitis. The e ffects of the competitive receptor antagonists des-Arg(9)[Leu(8)]-Bk ( B-1) and HOE 140 (B-2) were tested both in prophylactic (pre-inflammat ion administration) and therapeutic (post-inflammation administration) scenarios. Compared with control animals, des-Arg(9)[Leu(8)]-Bk had n o effect on the hyper-reflexic response of the bladder to inflammation unless it was administered 5 h after inflammation. However, HOE 140 w as able to attenuate the inflammation-induced viscero-visceral hyper-r eflexia (VVH at doses of 1 mg/kg, 2 mg/kg and 7.5 mg/kg. This effect w as apparent whether the drug was administered before, or after inflamm ation. In contrast, neither compound was effective in attenuating the intravesical plasma extravasation induced by turpentine. The data ther efore suggest that the VVH and tissue inflammation responses are media ted via different mechanisms. In addition, the turpentine-induced VVH appears to be mediated, at least partially, by the B-2 receptor in the early phase, with the B-1 receptor only becoming important later. (C) 1998 International Association for the Study of Pain. Published by El sevier Science B.V.