EFFECTS OF ANTI-INFLAMMATORY DRUGS ON THE LAME WALKING REACTION IN ADJUVANT-INDUCED EDEMATOUS RATS

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Abstract
Acute inflammatory paw edema of rats was formed by the injection of 0.5% Mycobacterium tuberculosis-liquid parraffin suspension into the hind paw, and then the pain threshold of he inflamed paw decreased. At that time, the rats showed a three-legged gait, i.e., the lame walking reaction. The reaction was inhibited by acidic nonsteroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and aspirin, inhibitors of prostaglandins biosynthesis, at a lower dose level than those in the Randall-Selitto test using yeast edematous rats and in the flexion tests using adjuvant arthritic or silver nitrate arthritic rats. Basic nonsteroidal anti-inflammatory drugs, e.g., tiaramide HCl, mepirizole and perisoxal citrate, not inhibitors of prostaglandins [PG] E biosynthesis, were less potent than the acidic nonsteroidal anti-inflammatory drugs in the inhibition of the lame walking reaction. When PGE2 was injected into the inflamed paw, the inhibitory effects of acidic non-steroidal anti-flammatory drugs on the reaction disappeared, but those of the basic nonsteroidal anti-inflammatory drugs did not disappear. Bradykinin had no influence on the effects of both acidic and basic nonsteroidal anti-inflammatory drugs in the inhibition of the reaction. Analgesic evaluation with the lame walking reaction is more sensitive than with the Randall-Selitto or the flection methods. Morphine, pentazocine and acetaminophen inhibited the reaction, and these effects did not disappear by the injection of PGE2 into the inflamed paw. PG play important roles in inflammatory pain, and the lameness test can serve as a new method for evaluating analgesics such as anti-inflammatory drugs and for investigating the mechanism of inflammatory pain.