人类疼痛实验模型方法及评价研究进展

Development of Human Experimental Pain Models

疼痛是各种疾病最常见的症状,是当今困扰人类健康最严重的问题之一。目前临床上应用的镇痛药种类有限,且大多具有镇痛效果不强和/或成瘾、耐受等明确的副作用,致使大量的疼痛患者得不到有效的治疗。因而急需开发新型不成瘾和副作用小的镇痛药。由于难以在人体对疼痛进行深入的机制和药效研究,往往通过建立疼痛的动物模型来筛选和鉴定镇痛候选药物。很多研究表明,根据动物疼痛模型的镇痛效果,很难预测其在人类身上的镇痛作用,导致临床研究常常出现令人困惑和模糊混乱的评价结果。新兴的人类疼痛实验模型,有望成为镇痛新药研发中联系动物实验和临床试验的有机桥梁,用于评价候选镇痛新药的作用机制和疗效,可为临床试验提供更加科学的设计方案,增加临床试验的成功率。该文拟对在健康志愿者身上进行的人类疼痛实验模型的研究进展进行综述,以期为加快新型镇痛药物的研发进程提供借鉴和参考。

Pain is the most common symptom of various diseases,which is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Limited analgesic medications were used in the clinic. The effects of these analgesics are often incomplete and complicated by serious side effects and/or tolerance. Thus, new types of analgesic drugs without addiction and serious side effects are desperately needed. It is hard to understand the basic biology of pain as well as to evaluate analgesic effects in human models. Therefore, animal models are widely used in the laboratory investigations to screen and identify new painkiller candidates. Animal pain models have shown low predictability for analgesic efficacy in humans, and clinical studies are confounded to interfere with the evaluation. Human experimental pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. The present review outlines the progress of human experimental pain models in healthy volunteers and addresses analgesic efficacy in patients, which would be helpful to speed up development of new types of analgesic drugs.