DEVELOPMENT OF A PRIMATE BEHAVIORAL NOCICEPTIVE ASSAY

灵长类动物行为伤害测定的开发

• 批准号: 2893458
• 负责人: David Clifford Yeomans
• 金额: $ 7.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2893458
• 关键词: C fiber; Macaca; behavior test; behavioral /social science research tag; capsaicin; chemoreceptors; ethology; morphine; pain threshold; psychopharmacology; technology /technique development; thermoreception; thermoreceptors

Over the last several years, the scientific literature has been replete with numerous new approaches to the treatment of pain. Unfortunately, approaches that were promising in the laboratory do not always translate to better clinical treatments. Similarly, the underlying physiology and clinical relevance of some animal pain models used to evaluate these new treatments have not been clearly demonstrated. One of the reasons for these disparities may have to do with the fact that some analgesic treatments appear to differentially attenuate only some kinds of nociception. Some standard tests then, may miss the potential utility of a treatment for a pain type that is not modeled by those tests. One distinction that we have found to be important in determining antinociceptive capacity of treatments is whether, and to what extent a nociceptive response is mediated by the activation of unmyelinated or myelinated primary afferent nociceptors. Another reason that results of rodent tests do not always predict clinical outcomes and vice versa may be the phylogenetic distance between humans and rodents. It is likely that testing potential treatments using non-human primates models might be more predictive of clincial utility in some cases. Thus, there is a need for the development of a primate assay which allows for the differential assessement of nociception mediated by myelinated or unmyelinated nociceptors. The purpose of the work outlined in this proposal is to provide preliminary evidence that the principles determined in rodents with regards to differential testing of Adelta and C fiber mediated nociception are also applicable to the testing of non-human primates. The experiments described here make use of demonstrated differences in the sensitivity of nociception mediated by myelinated or unmyelinated nociceptors to different rates of skin heating, topical application of the neurotoxin capsaicin, and the systemic application of the opiate analgesic morphine. The goal of this work is to develop a primate nociceptive assay which will allow for better predictions of the clinical utility of novel approaches to the treatment of pain.

在过去的几年里，科学文献中充满了许多治疗疼痛的新方法。不幸的是，在实验室中有希望的方法并不总是转化为更好的临床治疗。同样，用于评估这些新治疗的一些动物疼痛模型的潜在生理学和临床相关性尚未得到明确证明。 这些差异的原因之一可能与某些镇痛治疗似乎只对某些种类的伤害性感受有不同的减弱作用有关。 因此，一些标准测试可能会错过那些测试未建模的疼痛类型的治疗的潜在效用。 我们已经发现在确定治疗的抗伤害感受能力中重要的一个区别是伤害感受反应是否以及在多大程度上由无髓鞘或有髓鞘的初级传入伤害感受器的激活介导。 啮齿类动物测试的结果并不总是预测临床结果，反之亦然的另一个原因可能是人类和啮齿类动物之间的系统发育距离。 在某些情况下，使用非人类灵长类动物模型测试潜在的治疗方法可能更能预测临床效用。因此，需要开发一种灵长类动物测定法，其允许对由有髓鞘或无髓鞘伤害感受器介导的伤害感受进行差异评估。本提案中概述的工作旨在提供初步证据，证明在啮齿动物中确定的关于Δ和C纤维介导的伤害感受差异试验的原则也适用于非人灵长类动物的试验。 这里描述的实验利用了有髓或无髓伤害感受器介导的伤害感受对不同速率的皮肤加热、神经毒素辣椒素的局部应用和阿片类镇痛剂吗啡的全身应用的敏感性的差异。 这项工作的目标是开发一种灵长类动物的伤害性试验，这将允许更好地预测新的方法来治疗疼痛的临床效用。