Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic agents generally lack efficacy and may have undesirable side effects. Traditional target-based drug discovery efforts that generate compounds with selectivity for single targets have a high rate of attrition because of their poor clinical efficacy. Here, we examine the challenges associated with the current analgesic drug discovery model and review evidence in favor of stem cell–derived neuronal-based screening approaches for the identification of analgesic targets and compounds for treating diverse forms of acute and chronic pain.

中文翻译：

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开发针对急性和慢性疼痛的伤害感受器选择性治疗

尽管致力于开发新的、非成瘾性镇痛药进行了大量努力，但在治疗疼痛方面的成功仍然有限。临床上可用的镇痛剂通常缺乏疗效并且可能具有不良副作用。传统的基于靶标的药物发现工作会产生对单一靶标具有选择性的化合物，但由于临床疗效不佳，因此失败率很高。在这里，我们研究了与当前镇痛药物发现模型相关的挑战，并回顾了支持基于干细胞衍生神经元的筛选方法的证据，以确定用于治疗各种形式的急性和慢性疼痛的镇痛靶点和化合物。