A Thermal Place Preference Test for Discovery of Neuropathic Pain Drugs.,ACS Chemical Neuroscience

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A Thermal Place Preference Test for Discovery of Neuropathic Pain Drugs.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-03-24 , DOI: 10.1021/acschemneuro.0c00013
Joel Caporoso ₁ , Mark Moses ₁ , Kerryann Koper ₁ , Tommy S Tillman ₁ , Lingling Jiang ₁ , Nicole Brandon ₁ , Qiang Chen ₁ , Pei Tang _{1,

2,

3} , Yan Xu _{1,

3,

4,

5}

Affiliation

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 in vitro surrogate targets, in vivo 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 in vivo screening of the next generation of pain medications.

中文翻译：

用于发现神经性疼痛药物的热放置偏好测试。

开发有效的非阿片类镇痛药是战胜慢性疼痛和当前阿片类药物危机的必不可少的一部分。尽管大多数筛选方法都使用体外替代靶标，但是体内筛选止痛药是药物开发中必要的临床前步骤。在这里，我们报告基于热场所偏好测试（TPPT）原理的新型自动行为测试设备的设计。这种新设计可以检测，量化和区分假动物和慢性收缩损伤（CCI）啮齿动物对冷刺激的行为反应，最多可同时测试12只动物。在12.5°C与30.0°C（±0.5°C）的最佳温度对下，TPPT设计在单独的10分钟测试中捕获了吗啡和普瑞巴林对CCI大鼠的镇痛作用。此外，它可以区分吗啡或普瑞巴林的镇痛作用与地西epa的抗焦虑作用。结果以及相对较低的制造设备成本和适度的高通量，使我们的TPPT设计适用于啮齿动物慢性疼痛的行为研究以及下一代止痛药的高通量体内筛选。

更新日期：2020-03-24

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