Posner John, Telekes Andras, Crowley Dominic, Phillipson Richard, Peck Anthony W
Department of Clinical Pharmacology, Wellcome Research Laboratories, Beckenham, KentU.K.
Pain. 1985 Sep;23(1):73-82. doi: 10.1016/0304-3959(85)90232-5.
The analgesic activity of an opiate was studied in 12 healthy volunteers using a cold-induced pain (CP) model. Effects on the central nervous system (CNS) were also measured. According to a double-blind, randomised, balanced, cross-over design with an interval of 7 days between occasions, subjects received single oral doses of 2, 4 and 8 mg dipipanone (D2, D4, D8) and a placebo. The CP test and a battery of measurements of CNS function were performed 3 times on each study day, once before and again 1.5 h and 3.0 h after treatment. Mean pain cores on a computerised visual analogue scale were significantly higher after placebo than those after 4 mg (P less than 0.05) and 8 mg (P less than 0.01) dipipanone and a dose-response relationship was evident. The opiate did not affect baseline blood pressure before the CP test but the hypertensive response to the painful cold stimulus was diminished 3 h after D8. Scores on scales for subjective assessment of alertness were significantly reduced 3 h after the 8 mg dose and pupil diameters were significantly smaller after all 3 doses of dipipanone. Body sway and visual near points were not significantly altered by the opiate. It is concluded that the CP test is a sensitive model for measurement of opiate-induced analgesia in healthy volunteers. Pupillometry and visual analogue scales are useful for the assessment of central effects of opiates.
采用冷诱导疼痛（CP）模型，在12名健康志愿者身上研究了一种阿片类药物的镇痛活性。同时还测量了其对中枢神经系统（CNS）的影响。根据双盲、随机、均衡、交叉设计，每次给药间隔7天，受试者分别单次口服2毫克、4毫克和8毫克地匹哌酮（D2、D4、D8）以及安慰剂。在每个研究日，CP测试和一系列中枢神经系统功能测量均进行3次，分别在治疗前、治疗后1.5小时和3.0小时各进行一次。在计算机化视觉模拟量表上，安慰剂后的平均疼痛评分显著高于4毫克（P<0.05）和8毫克（P<0.01）地匹哌酮后的评分，且呈现明显的剂量反应关系。阿片类药物在CP测试前不影响基线血压，但在D8给药后3小时，对疼痛冷刺激的高血压反应减弱。8毫克剂量给药后3小时，警觉性主观评估量表得分显著降低，且所有3个剂量的地匹哌酮给药后瞳孔直径均显著变小。阿片类药物对身体摇摆和视觉近点无显著影响。得出结论，CP测试是测量健康志愿者中阿片类药物诱导镇痛的敏感模型。瞳孔测量和视觉模拟量表有助于评估阿片类药物的中枢效应。
