Re-appraisal of the role of histamine in carrageenan-induced paw oedema.

A single sub-plantar injection of 1% carrageenan in saline produced a bi-phasic paw volume increase, phase 1 plateauing at 0.5-1 h, phase 2 at 3-6 h. Subtraction of the non-specific contralateral paw response produced by saline injection revealed a monophasic carrageenan response. Mepyramine maleate at a dose maximally effective on histamine-induced paw oedema (1 mg X kg-1 i.p.) failed to suppress carrageenan-induced inflammation. Maximally effective doses of cimetidine HCl (1-100 mg X kg-1) suppressed the response by no more than 53%. In animals treated with cimetidine HCl (1 mg X kg-1), pretreatment with indomethacin (2.5 mg X kg-1) further suppressed the mean oedema response by 59% compared with cimetidine alone. The indomethacin dose suppressed mean volume increase by 41%. Mepyramine alone or combined with cimetidine showed no anti-inflammatory activity. Following pretreatment with indomethacin (2.5 mg X kg-1), mepyramine maleate further suppressed the carrageenan oedema by 41% compared with indomethacin alone. While supporting a role for prostanoid formation, or other indomethacin-sensitive mechanisms, the results show that the mechanism of carrageenan-induced rat paw oedema also involves histamine acting largely through H2-receptors, although a role for H1-receptors can not be excluded. The interaction between mepyramine and indomethacin is discussed.