A STUDY OF THE ANALGESIA, SUBJECTIVE DEPRESSION, AND EUPHORIA PRODUCED BY MORPHINE, HEROINE, DILAUDID AND CODEINE IN THE NORMAL HUMAN SUBJECT

¹ From the Department of Pharmacology of the University of Wisconsin, Madison

A technique is presented, and its advantages and limitations described, whereby the von Frey hairs are utilized in establishing the average pain threshold on five sensitive face spots. This procedure is applicable in a reasonably quantitative manner to the study of the rapidity of onset, intensity, and duration of action of analgesia produced by drug action in the normal human subject.

Morphine, heroine, codeine and dilaudid have been studied following both subcutaneous and intravenous injection in eight subjects as regards the analgesia, subjective depression, euphoria, and side actions produced by these four drugs.

The subcutaneous dosages of the four drugs which produced a comparable elevation of the pain threshold were as follows: morphine sulphate, 10 mgm.; heroine hydrochloride, 1 to 2 mgm.; dilaudid hydrochloride, 0.8 to 1 mgm.; codeine phosphate, 64 mgm.

On this dosage basis, these drugs appear to be potent in the order named with respect to the following qualities. Duration of action. Morphine, dilaudid, codeine and heroine. Duration and intensity of subjective depression. Morphine, dilaudid, heroine and codeine. Euphoria. Heroine, morphine, dilaudid and codeine. Side actions. Morphine, dilaudid, codeine and heroine.

The average time interval which must elapse after subcutaneous injection of the four drugs before the maximum elevation of the pain threshold occurs, is as follows: Heroine, thirty minutes; codeine, thirty to sixty minutes; morphine, sixty to ninety minutes; dilaudid, ninety minutes. After intravenous injection, the peak of analgesia occurs at twenty minutes with all four drugs. In addition to the latter fact, evidence is presented to show that the variations between subcutaneous and intravenous administration result primarily from differences in the absorption rate from the skin area.

Intravenous differs from subcutaneous administration of the above doses of the four drugs as follows: 1. A less pronounced and less prolonged elevation of the pain threshold occurs, the rise being relatively the same with morphine, dilaudid and codeine, whereas heroine is almost as effective as if given under the skin. 2. Greater subjective depression for a short period and less euphoria occurs, the drugs having the same order of potency as for subcutaneous administration.

The analgesic action of these compounds appears to involve an influence upon a different mechanism than that which is responsible for subjective depression or narcosis, since no absolute correlation between the two could be made.

In a few experiments, where scopolamine was administered alone, an intense subjective depression was produced which tended to lower rather than to raise the pain threshold. No potentiation of the morphine curve was obtained when the two drugs are given simultaneously.

The observation of Mullin and Luckhardt that hypersensitivity to painful stimuli is a common sequel to a previous drug elevation of the pain threshold, is confirmed.

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