NOCICEPTIVE THRESHOLDS AS AFFECTED BY PARENTERAL ADMINISTRATION OF IRRITANTS AND OF VARIOUS ANTINOCICEPTIVE DRUGS

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

When compounds are tested for analgesic activity, misleading results may be obtained if the drugs are injected intraperitoneally. Morphine is only half as potent by the i.p. route as when given subcutaneously in rats.

On the other hand, parenteral administration of a substance which produces irritation or inflammation may yield results which can be mistakenly interpreted as evidence that the injected compound is a centrally acting analgesic drug. For example, the reaction threshold to a tail pinch in rats was markedly increased by the injection of 0.1 ml of 3% formalin into the foot. or by the intraperitoneal injection of stearic acid or phenyiquinone. The effect of the fonnalin and morphine enhanced each other; the action of intraperitoneal irritants was found to be dose-related.

Indomethacin, aminopyrine, acetophenetidine, and mefenamic acid raised the reaction threshold to tail pinch when the drugs were administered intraperitoneally, but mefenamic acid was inactive orally, even in relatively high doses. In the yeast-inflamed foot analgesic assay, indomethacin, flufenamic acid, mefenamic acid and aspirin raised the threshold for response to pressure applied to the inflamed foot; indomethacin was the most potent of the group. None of these compounds increased the response threshold of the normal foot, in contrast to the action of morphine. There was no evidence that any of these nonnarcotic analgesics was effective by a different mechanism than the others.

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