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超越啮齿动物疼痛模型:用于评估新型镇痛疗法和阐述疼痛机制的非人类灵长类动物模型。

Beyond rodent models of pain: non-human primate models for evaluating novel analgesic therapeutics and elaborating pain mechanisms.

机构信息

Hamamatsu Pharma Research, Kita-ku, 1-3-7 Shinmiyakoda, Hamamatsu 431-2103, Japan.

出版信息

CNS Neurol Disord Drug Targets. 2013 Dec;12(8):1257-70. doi: 10.2174/18715273113129990111.

Abstract

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested that there be greater utilization of non-human primates (NHP) in preclinical pain studies. Methods to induce chronic pain-like states and quantify changes in nociception that have been developed in rodents could be adapted to the NHP. Similarly, human experimental injury-induced sensitization, which attempts to temporarily mimic the neuropathology and symptoms observed in the chronic pain state, could be adapted to the NHP. The NHP could then serve as a platform to validate human experimental models as well as proof-of-concept studies. Beyond experimentally modeled pain states, a number of naturally occurring disease states, such as osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis testing and proof-of-concept studies. While NHP studies are logistically cumbersome, it is envisioned that NHP pain models will add value to current preclinical data and greatly facilitate the discovery of novel analgesic treatments.

摘要

评估潜在的镇痛治疗方法和阐述疼痛的神经生物学在很大程度上依赖于在啮齿动物中开发的疼痛模型。然而,啮齿动物的一个局限性是它们与人类在进化上的距离较远,这可能部分解释了一些临床前发现未能转化为临床应用的原因。相比之下,鉴于非人类灵长类动物(NHP)与人类在遗传上的接近性和表型上的相似性,建议在临床前疼痛研究中更多地利用 NHP。已经在啮齿动物中开发的用于诱导慢性疼痛样状态和量化伤害感受变化的方法可以适应 NHP。同样,试图暂时模拟慢性疼痛状态中观察到的神经病理学和症状的人类实验性损伤诱导敏化也可以适应 NHP。然后,NHP 可以作为验证人类实验模型以及概念验证研究的平台。除了实验性模拟的疼痛状态外,一些自然发生的疾病状态,如骨关节炎,在 NHP 中表达,这可以用于假设检验和概念验证研究。虽然 NHP 研究在操作上很繁琐,但预计 NHP 疼痛模型将为当前的临床前数据增加价值,并极大地促进新型镇痛治疗方法的发现。

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