The Ann Hayes Consultancy, St Johns Innovation Centre, Cambridge, UK.
Center for Sensory-Motor Interaction, Department of Health Science and Technology, School of Medicine, Aalborg University, Fredrik BajersVej 7, Bld. D3, DK-9220 Aalborg E, Denmark.
Curr Opin Pharmacol. 2014 Feb;14:11-7. doi: 10.1016/j.coph.2013.09.017. Epub 2013 Oct 23.
Recent advances in understanding the pathophysiology of pain have led to a wealth of molecular targets for novel analgesic drugs and many clinical drug trials. There have been successes, like the gabapentinoids for neuropathic pain and calcium channel blockers for otherwise intractable pain states; and drugs which show promise in clinical trials, like nerve growth factor inhibitors and p38 kinase inhibitors. Unfortunately there have also been a number of failures. We suggest factors which might predispose to success, for example some clinical precedence for the mechanism in pain or a genetic link for the mechanism, for example a mutation linked to a pain syndrome. We also stress the importance of demonstrating molecular target engagement with a novel compound and suggest pain biomarkers which can be used for mechanistic drug profiling.
近年来，人们对疼痛病理生理学的认识不断深入，为新型镇痛药的研发提供了大量的分子靶点，并开展了许多临床药物试验。其中一些取得了成功，例如加巴喷丁类药物治疗神经病理性疼痛，钙通道阻滞剂治疗其他难以治疗的疼痛状态；还有一些药物在临床试验中显示出了前景，例如神经生长因子抑制剂和 p38 激酶抑制剂。但不幸的是，也有一些药物试验失败了。我们提出了一些可能有助于成功的因素，例如某种机制在疼痛方面的临床前例，或者某种机制的遗传关联，例如与疼痛综合征相关的基因突变。我们还强调了用新型化合物证明分子靶点结合的重要性，并提出了可用于药物作用机制分析的疼痛生物标志物。
