Munro Gordon, Jansen-Olesen Inger, Olesen Jes
Department of Neurology, Danish Headache Center, Glostrup Research Institute, Nordre Ringvej 69, 2600 Glostrup, Denmark.
Department of Neurology, Danish Headache Center, Glostrup Research Institute, Nordre Ringvej 69, 2600 Glostrup, Denmark.
Drug Discov Today. 2017 Jul;22(7):1103-1111. doi: 10.1016/j.drudis.2017.04.016. Epub 2017 May 2.
Preclinical research activities in relation to pain typically involve the 'holy trinity' of nociceptive, inflammatory and neuropathic pain for purposes of target validation and defining target product profiles of novel analgesic compounds. For some reason it seems that headache or migraine are rarely considered as additional entities to explore. Frontline medications used in the treatment of, for example, inflammatory pain, neuropathic pain and migraine (NSAIDs versus pregabalin/duloxetine versus triptans) reveal distinct differences in pathophysiology that partially explain this approach. Nevertheless, for many patients enduring chronic pain, regardless of aetiology, high unmet needs remain. By focusing more on commonalities shared between neuropathic pain and headache disorders such as migraine, drug discovery efforts could be spread more efficiently across a larger indication area. Here, some of the most commonly used models and methods employed within 'pain and migraine' drug development will be presented. Recent advances within these disciplines suggest that, with the addition of a few extra carefully chosen ancillary models and/or endpoints, the relative value in terms of resources used, reciprocal flow of information and net worth of a 'typical' package could be increased substantially for the pain and migraine fields.
与疼痛相关的临床前研究活动通常涉及伤害性疼痛、炎性疼痛和神经性疼痛这“三位一体”,目的是进行靶点验证并确定新型镇痛化合物的靶点产品概况。出于某种原因,头痛或偏头痛似乎很少被视为需要探索的额外实体。用于治疗例如炎性疼痛、神经性疼痛和偏头痛的一线药物(非甾体抗炎药与普瑞巴林/度洛西汀与曲坦类药物)在病理生理学上显示出明显差异,这部分解释了这种方法。然而,对于许多忍受慢性疼痛的患者来说,无论病因如何,未满足的需求仍然很高。通过更多地关注神经性疼痛和偏头痛等头痛疾病之间的共性,可以更有效地将药物研发工作扩展到更大的适应症领域。在此,将介绍“疼痛与偏头痛”药物研发中一些最常用的模型和方法。这些学科的最新进展表明,通过增加一些精心挑选的额外辅助模型和/或终点指标,对于疼痛和偏头痛领域而言,“典型”方案在资源使用、信息交互以及净值方面的相对价值可能会大幅提高。