Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kohbata, Aomori-shi, Aomori, 030-0943, Japan.
Center for Brain and Health Sciences, Aomori University, 109-1 Takama, Ishie, Aomori-shi, Aomori, 038-0003, Japan.
Drug Dev Res. 2018 Jun;79(4):147-156. doi: 10.1002/ddr.21429. Epub 2018 May 6.
Preclinical Research & Development Chronic pain is a major health and socioeconomic burden because of its high prevalence, negative influence on patients' physical and/or emotional conditions, and huge costs to society. The responses of chronic pain patients to analgesic therapies vary substantially from individual to individual, and no more than a minority of chronic pain patients with various etiologies such as neuropathy and inflammation are, in fact, successfully relieved by existing drugs including opioid analgesics, nonopioid analgesics, antiepileptics, and antidepressants. The large primary unmet medical need would therefore be the patient domain that does not respond well to existing drugs. Accordingly, the expected profile for innovative analgesics would not be efficacy in the responder patient domain, but significant efficacy in patients with existing drug-resistant chronic pain. Meanwhile, the current gold standard in preclinical pain measures for the screening of analgesic candidates is existing drug-sensitive pain measures in animal models of chronic pain. Analgesic candidates screened using such preclinical pain measures during the last decades have been far from fulfilling the expected profile for innovative analgesics. Given that it is unlikely that such existing drug-sensitive pain measures are the best approach to developing innovative analgesics, one of the other approaches would be giving priority to existing drug-resistant pain measures in preclinical research. This review introduces potentially applicable existing drug-resistant pain measures published so far and suggests that the use of them would lead to the development of innovative analgesics.
临床前研究与开发
慢性疼痛是一种主要的健康和社会经济负担，因为它的高发病率、对患者身体和/或情绪状况的负面影响，以及对社会的巨大成本。慢性疼痛患者对镇痛治疗的反应个体差异很大，而且实际上，各种病因（如神经病变和炎症）的慢性疼痛患者中，只有少数人能够通过现有的药物（包括阿片类镇痛药、非阿片类镇痛药、抗癫痫药和抗抑郁药）得到有效缓解。因此，大量未满足的主要医疗需求将是对现有药物反应不佳的患者领域。因此，创新型镇痛药的预期特征不是在应答患者领域的疗效，而是在现有药物耐药性慢性疼痛患者中的显著疗效。
同时，目前用于筛选镇痛候选药物的临床前疼痛测量的黄金标准是慢性疼痛动物模型中的现有药物敏感疼痛测量。在过去几十年中，使用这些临床前疼痛测量筛选的镇痛候选药物远未达到创新型镇痛药的预期特征。鉴于不太可能将这些现有的药物敏感疼痛测量作为开发创新型镇痛药的最佳方法之一，另一种方法是在临床前研究中优先考虑现有的药物耐药性疼痛测量。
本综述介绍了迄今为止已发表的潜在适用的现有药物耐药性疼痛测量方法，并提出使用这些方法将有助于开发创新型镇痛药。
