Multiple toe-pinch method for testing analgesic drugs.

In guinea-pigs and rats, an immediate squeak was one of the most consistent and readily observed responses to application of a light artery clip to the base of a toe. Morphine and related drugs suppressed this response. Squeak-responses from each toe of an experimental animal formed the basis of a technique for measuring activity of analgesic drugs. A statistical method was developed to analyse the correlated quantal observations obtained. It provided an estimate of the increase of information from several toes compared with one. Testing all toes of each animal yielded a substantial increase of information, because the correlation between responses of different toes was low. Among drugs having an analgesic action in man, 1-(beta-diethyl-aminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole, methadone, morphine, pethidine and codeine (in descending order of potency) were active in this test in guinea-pigs. Acetylsalicylic acid, amidopyrine, amphetamine, chlorpromazine, 4-hydroxyisophthalic acid, lysergic acid diethylamide, mephenesin, nalorphine, pentetrazole, phenobarbitone, phencyclidine, phenytoin, salicylamide, strychnine and troxidone showed little or no activity. The time-courses of active drugs were estimated, and morphine had the longest action.