Divergent profiles of fentanyl withdrawal and associated pain in mice and rats.
Divergent profiles of fentanyl withdrawal and associated pain in mice and rats.
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DOI：
10.1016/j.pbb.2020.173077
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Cramer N
中科院分区：
文献类型：
--
作者：
Uddin O;Jenne C;Fox ME;Arakawa K;Keller A;Cramer N
阿片类药物滥用对患者、他们的家人和社会都有毁灭性的影响。戒断症状是非常不愉快的，持续时间长，经常阻碍康复或导致复发。由于非法使用芬太尼等强效合成阿片类药物而导致的滥用和过量使用急剧增加，这突出表明迫切需要了解与这些药物有关的戒断机制。在不同的临床前模型中，关于阿片类药物戒断的报道不一致，阻碍了进展。在这里，我们使用大鼠和小鼠，在间歇性使用芬太尼两周后，我们量化了自发戒断和纳洛酮催促戒断期间的戒断行为。我们发现，小鼠和大鼠在暴露期间体重都有所下降，并在自发和纳洛酮催促戒断过程中表现出更多的痛苦迹象。然而，这些物种在与戒断相关的疼痛的表达上有所不同，这是人类复发的关键因素。在两种戒断状态下，自发性或持续性疼痛在大鼠中优先表达，而在小鼠中没有观察到变化。相反，与戒断相关的热痛觉过敏只在小鼠身上发现。这些数据表明，大鼠和小鼠在经历戒断的方式以及它们最准确地模拟人类状况的哪些方面方面存在差异。这些差异突出了每个物种作为模型系统的优势，并可以为阿片类药物戒断研究的实验设计提供参考。
Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species’ strengths as model systems and can inform experimental design in studies of opioid withdrawal.
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影响因子：
4.8
作者：
Deuis JR;Dvorakova LS;Vetter I
通讯作者：
Vetter I
DOI：
10.1111/j.1476-5381.1960.tb00277.x
发表时间：
1960-01-01
期刊：
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子：
--
作者：
BILBEY, DLJ;SALEM, H;GROSSMAN, MH
通讯作者：
GROSSMAN, MH
影响因子：
2.1
作者：
Diaz, Silvina L.;Hermida, Maria P.;Balerio, Graciela N.
通讯作者：
Balerio, Graciela N.
影响因子：
2.5
作者：
Bobzean, Samara A. M.;Kokane, Saurabh S.;Perrotti, Linda I.
通讯作者：
Perrotti, Linda I.
影响因子：
2.3
作者：
Carcoba, Luis M.;Contreras, Arturo E.;Meagher, Mary W.
通讯作者：
Meagher, Mary W.