REACTION THRESHOLDS TO PRESSURE IN EDEMATOUS HINDPAWS OF RATS AND RESPONSES TO ANALGESIC DRUGS

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

Concurrent measurements were made of edema volume and reaction threshold to pressure in the hind paws of rats at various times after subplantar injection of phlogistic agents. Changes in threshold did not parallel changes in foot volume ; hyperesthesia was seen after carrageenin and mustard, transient hypoesthesia followed by hyperesthesia after yeast, and only hypoesthesia after egg white, serotonin, or dextran in the concentrations used.

Indomethacin in oral doses up to 3 mg/ kg was administered after time had been allowed for development of edema. Under these circumstances, indomethacin did not change the edema volume, but it markedly raised the threshold in feet injected with yeast, mustard or carrageenin. In the hindpaws injected with serotonin, egg white or dextran, in which an elevated threshold was already present, indomethacin did not further increase it, nor did it raise the threshold in noninflamed feet.

The narcotic antagonists nalorphine, pentazocine, cyclazocine, N-cyclopropylmethylnor-morphine, and (-)-3-hydroxy-N-cyclopropyl-methylmorphinan raised the threshold in yeast-induced hyperesthesia, but did not affect threshold in the normal feet; (-)-3-hydroxy-N-cyclopropylmethylisomorphinan was inactive, while morphine and d-propoxyphene increased the thresholds in noninflamed as well as in inflamed feet. In their effects in this test, the narcotic antagonists resemble nonnarcotic analgesics.

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