Stacher G, Steinringer H, Schneider S, Mittelbach G, Winklehner S, Gaupmann G
Br J Clin Pharmacol. 1986 Jan;21(1):35-43. doi: 10.1111/j.1365-2125.1986.tb02820.x.
Models with experimentally induced pain in healthy man might be useful for the screening for analgesic effects of new drugs. Experimental pain models have been shown to discriminate reliably between the effects of opioid analgesics and placebo but their sensitivity to nonsteroidal anti-inflammatory agents is disputed. This study investigated whether it would be possible by using electrically and thermally induced cutaneous pain to discriminate reliably the effects of single oral doses of 75 and 150 mg diclofenac sodium on the one hand and 60 mg codeine on the other from those of placebo. Forty-eight healthy subjects participated each in four experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised eight series of measurements, two before and six after drug administration, carried out at 30 min intervals. Diclofenac sodium produced significant dose-related increases of threshold and tolerance to electrically and threshold to thermally induced pain. Codeine 60 mg was significantly superior to placebo in all pain measures. Its analgesic effects were stronger than those of diclofenac 75 mg but weaker than those of diclofenac 150 mg. Neither 150 mg nor 75 mg diclofenac caused more side effects than placebo, whereas codeine 60 mg elicited a high frequency of side effects. No severe adverse effects occurred after any one treatment. The results suggest that both electrically and thermally induced cutaneous pain are well suited to evaluate analgesic effects not only of opioids but also of nonsteroidal anti-inflammatory drugs.
在健康人体上建立实验性疼痛模型可能有助于筛选新药的镇痛效果。实验性疼痛模型已被证明能够可靠地区分阿片类镇痛药和安慰剂的效果,但它们对非甾体抗炎药的敏感性仍存在争议。本研究调查了通过电刺激和热刺激诱发皮肤疼痛,是否能够可靠地区分单次口服75毫克和150毫克双氯芬酸钠以及60毫克可待因与安慰剂的效果。48名健康受试者分别参与了四项实验,在实验中他们以随机双盲的方式接受了每种治疗。每项实验包括八组测量,给药前两组,给药后六组,每隔30分钟进行一次。双氯芬酸钠使对电刺激诱发疼痛的阈值和耐受性以及对热刺激诱发疼痛的阈值产生了显著的剂量相关增加。60毫克可待因在所有疼痛测量指标上均显著优于安慰剂。其镇痛效果强于75毫克双氯芬酸钠,但弱于150毫克双氯芬酸钠。150毫克和75毫克双氯芬酸钠引起的副作用均不比安慰剂多,而60毫克可待因引起副作用的频率较高。任何一种治疗后均未出现严重不良反应。结果表明,电刺激和热刺激诱发的皮肤疼痛不仅适用于评估阿片类药物的镇痛效果,也适用于评估非甾体抗炎药的镇痛效果。