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Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

机译：芬太尼戒断和小鼠和大鼠相关疼痛的分歧谱

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摘要

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.
机译：阿片类药物滥用对患者、他们的家庭和社会都有毁灭性的影响。戒断症状严重不愉快，持续时间长，经常阻碍康复或导致复发。非法使用芬太尼等强效、快速作用的合成阿片类药物导致滥用和过量的急剧增加，突显了了解与这些药物有关的戒断机制的紧迫性。在不同的临床前模型中，关于阿片类药物戒断的不一致报道阻碍了进展。在这里，我们使用雄性和雌性大鼠，在间歇性芬太尼暴露两周后，对自发戒断和纳洛酮促戒断期间的戒断行为进行了量化。我们发现，小鼠和大鼠在暴露期间体重减轻，并在自发和纳洛酮促发的戒断期间表现出更多的痛苦迹象。然而，这些物种在戒断相关疼痛的表达上存在差异，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优先在大鼠中表达，而在小鼠中未观察到变化。相比之下，仅在小鼠中发现与戒断相关的热痛觉过敏。这些数据表明，大鼠和小鼠在如何体验戒断以及他们最准确地模拟人类条件的哪些方面存在差异。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信息。

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    Uddin Olivia; Jenne Carleigh; Fox Megan E.; Arakawa Keiko; Keller Asaf; Cramer Nathan;

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    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

    Univ Maryland Sch Med Program Neurosci Dept Anat &

    Neurobiol 20 Penn St Baltimore MD 21201 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
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