Premium
Evidence for participation of B 1 and B 2 kinin receptors in formalin‐induced nociceptive response in the mouse
Author(s) -
Corrêa Clóvis R.,
Calixto João B.
Publication year - 1993
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.1476-5381.1993.tb13791.x
Subject(s) - kinin , bradykinin , receptor , chemistry , antagonist , pharmacology , b2 receptor , nociception , substance p , kallidin , receptor antagonist , endocrinology , medicine , biochemistry , neuropeptide
1 This study was designed to investigate the role of bradykinin (BK), as well as the subtype of BK receptors involved, in formalin‐induced hindpaw pain in the mouse by use of selective B 1 and B 2 receptor antagonists. In addition, we have analysed whether or not BK may be involved in formalin‐induced hindpaw oedema in the mouse. 2 The pretreatment of animals with captopril (2 and 5 mg kg −1 , s.c.) significantly increase the first and the second phases of formalin‐induced pain. 3 Co‐injection of the selective B 1 receptor antagonist des‐Arg 9 [Leu 8 ]‐BK (0.2–0.4 nmol/paw), together with formalin, caused graded and similar inhibitions of both phases of formalin‐induced pain. Similar results were obtained with the B 2 antagonists NPC 349 ( d ‐Arg[Hyp 3 ,Thi 5,8 ‐ d ‐Phe 7 ]‐BK) and NPC 567 ( d ‐Arg[Hyp 3 , d ‐Phe 7 ]‐BK) (0.2 and 0.6 nmol/paw). Higher concentrations of these antagonists (1 nmol/paw) failed to antagonize formalin‐induced pain. 4 The new potent and selective B 2 receptor antagonists, Hoe 140 ( d ‐Arg[Hyp 3 ,Thi 5 , d ‐Tic 7 ,Oic 8 ]‐BK), NPC 17731 ( d ‐Arg[Hyp 3 , trans ‐4‐propoxy‐ d ‐proline ( transpropyl ) 7 , Oic 8 ]‐BK), and NPC 17761 ( d ‐Arg[Hyp 3 , trans ‐4‐propoxy‐ d ‐proline ( trans thiophenyl) 7 , Oic 8 ]‐BK) (0.02 to 1.0 nmol/paw), also caused significant inhibitions of both phases of formalin‐induced pain. When Hoe 140 was injected subcutaneously 30 min before formalin injection (9.9 and 99 nmol kg −1 ), it significantly attenuated both phases of formalin‐induced pain. The putative non‐peptide BK antagonist, MV 8612 (1.6 to 9.6 nmol/paw), but not MV 8608 (5.5 to 33 nmol/paw), caused a graded inhibition of both phases of formalin‐induced pain, being, however, more active against the first phase. 5 The pretreatment of animals with morphine (2.6 to 13μmol kg −1 , s.c.) caused dose‐dependent and equipotent inhibitions of both phases of formalin‐induced pain. In contrast, indomethacin (2.7 to 27 μmol kg −1 ) antagonized only the second phase of formalin‐induced pain. 6 The B 2 receptor antagonists, Hoe 140, NPC 17731, NPC 17761, NPC 349 and NPC 567, all caused a significant inhibition of formalin‐induced hindpaw oedema. A similar inhibition was also observed with indomethacin but not with captopril or morphine. 7 Our results provide strong evidence for the important role of endogenous BK, acting through both B 1 and B 2 receptors, in the genesis of both phases of formalin‐induced persistent pain in the mouse. In addition, the current results also demonstrate that the inflammatory oedema associated with the later phase of formalin‐induced pain seems to be mediated by endogenous BK, via activation of B 2 receptors.