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1 The Wellcome Research Laboratories, Burroughs Wellcome and Company (U.S.A.) Inc., Tuckahoe, New York
Accumulation of edema fluid as a function of time after the subplantar injection of 0.50 mg of carrageenin in rats is biphasic. The first phase begins immediately after injection of the irritant and diminishes in an hour. The second period of accelerated edema formation begins at the end of the 1st hr and persists through the 3rd hr. The first phase accounts for approximately 40% of the total edema volume produced in 3 hr. Foot skin temperature measurements taken after the subplantar administration of carrageenin gave a biphasic increase with time. Peak temperatures coincided with the two periods of rapid edema development and the trough with the interperiod. Hydrocortisone did not inhibit development of the first phase of edema but was a potent inhibitor of the second. Acetylsalicylic acid was active against both phases. Phenylbutazone produced slight inhibition of the first phase, which was not dose-dependent, but strongly inhibited the second phase. Each of these standard antiinflammatory drugs produced more than 75% inhibition of the second phase at the highest dose used. A brief period of complete suppression was recorded for hydrocortisone and phenylbutazone. Indomethacin induced strong dose-dependent inhibition of the second phase at doses which did not affect the development of the first phase. When carrageenin was charred by heat treatment at 130°C for 16 hr, it elicited the full first phase edema volume without subsequent development of the second phase. This indicates that the second phase is not a consequence of processes initiated during the first phase but is dependent on the structural integrity of the irritant molecule.
Submitted on June 20, 1968
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