Hunskaar Steinar, Hole Kjell
Department of Physiology, University of Bergen, N-5009 BergenNorway.
Pain. 1987 Jul;30(1):103-114. doi: 10.1016/0304-3959(87)90088-1.
The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non-inflammatory pain.
小鼠福尔马林试验是一种有效且可靠的伤害感受模型，对各类镇痛药都很敏感。有害刺激是在右后爪背侧皮下注射稀释的福尔马林（1%生理盐水溶液）。反应是动物舔注射爪的时间。可以识别出两个明显的高舔舐活动期，一个早期阶段持续注射福尔马林后的前5分钟，一个晚期阶段持续20至30分钟。为了阐明炎症过程在这两个阶段中的作用，我们分别在两个阶段测试了不同类别的药物。吗啡、可待因、奈福泮和奥芬那君作为中枢性镇痛药的例子，在两个阶段都具有抗伤害感受作用。相比之下，非甾体抗炎药吲哚美辛和萘普生以及类固醇地塞米松和氢化可的松仅抑制晚期阶段，而乙酰水杨酸（ASA）和对乙酰氨基酚在两个阶段都具有抗伤害感受作用。结果表明，福尔马林试验中的两个阶段可能具有不同的伤害感受机制。有人认为早期阶段是由于对伤害感受器的直接作用，并且在此阶段前列腺素不起重要作用。晚期阶段似乎是一种伴有炎症性疼痛的炎症反应，可被抗炎药抑制。ASA和对乙酰氨基酚似乎具有独立于其对前列腺素合成抑制作用的作用，并且它们对非炎症性疼痛也有影响。
