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, and B2 receptor antagonists. In addition, we have analysed whether or not BK may be involved in formalininduced hindpaw oedema in the mouse. 2 The pretreatment of animals with captopril (2 and 5 mg kg-', s.c.) significantly increase the first and the second phases of formalin-induced pain. 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-'), 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 formalininduced pain, being, however, more active against the first phase.5 The pretreatment of animals with morphine (2.6 to 13 #zmol kg-', s.c.) caused dose-dependent and equipotent inhibitions of both phases of formalin-induced pain. In contrast, indomethacin (2.7 to 27 limol kg -) antagonized only the second phase of formalin-induced pain.6 The B2 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, and B2 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 B2 receptors.

1 The purpose of this study was to investigate the topical and systemic anti-hyperalgesic effect of the newly-developed pseudopeptide B2 receptor antagonist, NPC 18688, in different models of nociception in mice.2 Given systemically 30 min beforehand, NPC 18688 (10-300 nmol kg-', i.p.) caused no agonist effect, but produced a dose-related and significant inhibition of abdominal constrictions caused by intraperitoneal injection of acetic acid (0.6%), acetylcholine (ACh, 4.5 mg kg-') or kaolin (50 mg kg-').

This study analyses the analgesic effect of a hydroalcoholic extract (HE) from Phyllanthus corcovadensis in several models of pain in mice. HE (3-60 mg kg-1, i.p.) or (100-500 mg kg-1, p.o.) caused a graded and potent analgesic effect against the abdominal constriction response caused by acetic acid and acetylcholine with an ID50 of about 3 and 100 mg kg-1, respectively. In the tail-flick model HE (up to 500 mg kg-1, p.o.) was without effect, while morphine (1-10 mg kg-1, s.c.) caused a graded increase in pain latency (ID50, 3 mg kg-1). HE (1-300 mg kg-1) given both intraperitoneally and orally caused a potent and graded inhibition of the second phase of formalin-induced persistent pain in mice with an ID50 of 1 and 80 mg kg-1, respectively. In contrast, morphine (1-5 mg kg-1, s.c.) inhibited both phases of formalin-induced pain with an ID50 of 2.5 mg kg-1. Indomethacin (1-10 mg kg-1, i.p.) only inhibited the second phase of formalin-induced pain with an ID50 of about 3 mg kg-1. The analgesic effect of indomethacin, but not that caused by morphine and HE was accompanied by a graded inhibition of formalin-induced mouse paw oedema. In addition, HE up to 1 g kg-1 failed to prevent carrageenan- and dextran-induced rat hindpaw oedema. It is concluded that HE exhibits a potent antinociceptive profile, either when given intraperitoneally or orally.(ABSTRACT TRUNCATED AT 250 WORDS)