Higuchi S, Osada Y, Shioiri Y, Tanaka N, Otomo S
Nihon Yakurigaku Zasshi. 1984 Aug;84(2):243-9.
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.
通过将0.5%结核分枝杆菌-液体石蜡悬液注射到大鼠后爪来形成急性炎症性爪水肿,然后炎症爪的痛阈降低。此时,大鼠表现出三足步态,即跛行反应。酸性非甾体抗炎药,如吲哚美辛、布洛芬和阿司匹林,这些前列腺素生物合成抑制剂,在比使用酵母水肿大鼠的兰德尔-塞利托试验以及使用佐剂性关节炎或硝酸银性关节炎大鼠的屈曲试验更低的剂量水平下就能抑制该反应。另一方面,碱性非甾体抗炎药,如盐酸替拉米特、美吡唑和枸橼酸哌索昔,它们不是前列腺素生物合成抑制剂,在抑制跛行反应方面比酸性非甾体抗炎药效力更低。当将前列腺素E2注射到炎症爪时,酸性非甾体抗炎药对该反应的抑制作用消失,但碱性非甾体抗炎药的抑制作用并未消失。缓激肽对酸性和碱性非甾体抗炎药抑制该反应的作用均无影响。用跛行反应进行的镇痛评价比用兰德尔-塞利托或屈曲方法更敏感。吗啡、喷他佐辛和对乙酰氨基酚抑制该反应,并且通过将前列腺素E2注射到炎症爪中这些作用并未消失。这些结果表明前列腺素在炎性疼痛中起重要作用,并且跛行试验可作为一种评估抗炎药等镇痛药以及研究炎性疼痛机制的新方法。