[Effects of anti-inflammatory drugs on the lame walking reaction in adjuvant-induced edematous rats].
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 the inflamed paw decreased. At that time, the rats showed a three-legged gait, namely, 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 flection tests using adjuvant arthritic or silver nitrate arthritic rats. On the other hand, basic nonsteroidal anti-inflammatory drugs, e.g., tiaramide HC1, mepirizole and perisoxal citrate, not inhibitors of prostaglandins biosynthesis, were less potent than the acidic nonsteroidal anti-inflammatory drugs in the inhibition of the lame walking reaction. When prostaglandin E2 was injected into the inflamed paw, the inhibitory effects of acidic non-steroidal anti-inflammatory drugs on the reaction disappeared, but those of the basic nonsteroidal anti-inflammatory drugs didn't 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 didn't disappear by the injection of prostaglandin E2 into the inflamed paw. These results suggest that prostaglandins 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.
D000700:Analgesics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced; D001169:Arthritis, Experimental / Q000188:drug therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004487:Edema / Q000188:drug therapy; D005534:Foot Diseases / Q000188:drug therapy; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012835:Silver Nitrate
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011453:Prostaglandins; D012835:Silver Nitrate