Pharmacological analysis of the acute inflammatory process induced in the rat's paw by local injection of carrageenin and by heating

Abstract

Summary1. Local injection of carrageenin in the rat's paw produced oedema and leakage of dye which had been administered previously by the intravenous route. A net dissociation between both parameters was observed: while oedema developed slowly, maximal intensity being attained after 4-5 h, dye-leakage was maximum after 1 hour. 2. Anti-inflammatory drugs such as acetylsalicylic acid and indomethacin were effective in reducing oedema and dye-leakage when given before the injection of carrageenin, but much less effective when given 30 or 60 min after carrageenin. Hexadimethrine bromide was effective in reducing dye-leakage also when given 1 h after the injection of carrageenin. 3. Combined administration of benadryl and methysergide, before the injection of carrageenin caused only a slight reduction in oedema and dye-leakage.4. When the paws were heated (550 C for 30 s) as a noxious stimulus the dissociation between maximal oedema and maximal dye-leakage was not observed, both phenomena running parallel. Pre-treatment of the animals with indomethacin did not afford any protection. 5. These results suggest that the inflammatory reaction to mild stimuli (carrageenin in our experiments) develops through different phases: initially the increased vascular permeability involves extravasation of plasma proteins and that phase is followed by an increased permeability mainly to water. Stronger stimuli (heating in our experiments) produce an overlapping of both phases, probably by inflicting severe damage to the vascular bed of the affected area.6. The anti-inflammatory drugs employed affected chiefly the initial phase of the response. 1fitroductionDyes injected intravenously localize in areas of developing inflammatory reactions. Using xylene as an irritant applied to the skin of rabbits, Rigdon (1939Rigdon ( , 1940 was able to show that Trypan blue and Indian ink concentrate in the injured areas only when injected into the circulation immediately after or within a period of less than 3-5 h following the application of xylene, though after that time these skin areas exhibited all the macroscopic and microscopic alterations associated with the inflammatory response. Rigdon concluded that increased vascular permeability is of brief duration following injury where xylene is applied.

A possible role of prostaglandins and bradykinin as a trigger of exudation in carrageenin-induced rat pleurisy

“…The involvement of bradykinin has been suggested in carrageenip-induced rat paw edema by depletion of kininogen [14][15][16]. It was also reported that prostaglandins were involved in carrageenin-induced inflammation in granuloma pouch of rats [17] and in carrageenin pleurisy [13,15], but the former work was not confirmed by others [18,19].…”

Anti-inflammatory and gastromucosal protective effects of Calotropis procera (Asclepiadaceae) stem bark

“…To investigate the effects of drugs on the acute phase of inflammation, models using pro-inflammatory agents such as carrageenan, dextran, formaldehyde, serotonin, histamine and bradykinin in rat paws are employed [4]. Carrageenan, a mucopolysaccharide, is perhaps the most commonly used and well-studied of these phlogistics [5], producing a maximal edema in 3 h. While the carrageenan model is typically associated with activation of the cyclooxygenase pathway and is sensitive to glucocorticoids and prostaglandin synthesis antagonists, the early phase of the carrageenan response is due to the release of serotonin and histamine [6].…”

Acute and chronic antiinflammatory effects of Hedera colchica in rats

“…Chronic inflammation models produced by implanting a foreign body under the skin are used to study the effects of a drug on the proliferation phase of inflammation (Suleyman et al, 1999). Carrageenan, a mucopolysaccaride, is perhaps the most commonly used and well studied of these phlogistics (Leme et al, 1973), producing a maximal edematous in 3 h. While the carrageenan model is typically associated with activation of the cyclo-oxygenase pathway and is sensitive to glucocorticoids and prostaglandin synthesis antagonists, the early phase of the carrageenan response is due to the release of serotonin and histamine (DiRosa et al, 1971).…”