Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
ACS Chem Neurosci. 2020 Apr 1;11(7):1006-1012. doi: 10.1021/acschemneuro.0c00013. Epub 2020 Mar 24.
Developing potent non-opioid pain medications is an integral part of the battle to conquer both chronic pain and the current opioid crisis. Although most screening approaches use surrogate targets, screening of analgesic candidates is a necessary preclinical step in drug discovery. Here, we report the design of a new automated behavioral testing apparatus based on the principle of a thermal place preference test (TPPT). This new design can detect, quantify, and differentiate behavioral responses to cold stimuli between sham and chronic constriction injury (CCI) rodents with up to 12 animals tested simultaneously. At an optimized temperature pair of 12.5 °C vs 30.0 °C (±0.5 °C), the TPPT design has captured the antinociceptive effects of morphine and pregabalin on CCI rats in individual 10 min tests. Moreover, it can differentiate analgesic effects by morphine or pregabalin from anxiolytic effects by diazepam. The results, along with the relatively low cost to construct the apparatus and moderately high throughput, make our TPPT design applicable for behavioral studies of chronic pain in rodents and for high-throughput screening of the next generation of pain medications.
开发有效的非阿片类止痛药是对抗慢性疼痛和当前阿片类药物危机的重要组成部分。虽然大多数筛选方法都使用替代靶标，但在药物发现中，对候选镇痛药的筛选是一个必要的临床前步骤。在这里，我们报告了一种新的自动化行为测试仪器的设计，该仪器基于热位置偏好测试（TPPT）的原理。这种新设计可以同时检测、量化和区分假手术和慢性缩窄性损伤（CCI）啮齿动物对冷刺激的行为反应，最多可同时检测 12 只动物。在优化的温度对（12.5°C 对 30.0°C（±0.5°C））下，TPPT 设计能够捕捉到吗啡和普瑞巴林对 CCI 大鼠在单次 10 分钟测试中的镇痛作用。此外，它还可以区分吗啡或普瑞巴林的镇痛作用与地西泮的抗焦虑作用。该结果以及构建仪器的相对低成本和中等高通量，使我们的 TPPT 设计适用于啮齿动物慢性疼痛的行为研究和下一代止痛药的高通量筛选。
