Hyperkatifeia, the manifestation of emotional distress or pain, is a conceptual framework gaining traction throughout the alcohol and other substance use fields as an important driver of addiction. It is well known that previous or current negative life experiences can serve as powerful motivators for excessive alcohol consumption and precipitate the development of an alcohol use disorder (AUD). A major hallmark of later stages of AUD is the emergence of hyperkatifeia during withdrawal, which can persist well into protracted abstinence to drive relapse. Given these complex interactions, understanding the specific neuroadaptations that lie at the intersection of hyperkatifeia and AUD can inform ongoing therapeutic development. The monoamine norepinephrine is of particular interest. Noradrenergic dysfunction is implicated in AUD, anxiety, chronic stress, depression, and emotional and physical pain. Importantly, there are key sexual dimorphisms within the noradrenergic system that are thought to differentially impact the development and trajectory of AUD in women and men. In the current review, we discuss past and recent work on noradrenergic influences at each stage of the AUD cycle (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation) through the lens of hyperkatifeia. Evidence from these studies support the prioritization of norepinephrine-specific drug development to treat AUD and the identification of AUD subpopulations that may benefit the most from these therapies (e.g., women or people with comorbid chronic pain or anxiety/stress disorders).

中文翻译：

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酒精使用障碍中 hyperkatifeia 的去甲肾上腺素能机制和回路


Hyperkatifeia 是情绪困扰或痛苦的表现，是一个概念框架，作为成瘾的重要驱动因素，在整个酒精和其他物质使用领域越来越受欢迎。众所周知，以前或现在的负面生活经历可以成为过量饮酒的强大动力，并促使酒精使用障碍 （AUD） 的发展。AUD 后期的一个主要标志是在戒断期间出现 hyperkatifeia，它可以持续到长期戒断以驱动复发。鉴于这些复杂的相互作用，了解位于 hyperkatifeia 和 AUD 交叉点的特定神经适应可以为正在进行的治疗开发提供信息。单胺去甲肾上腺素特别令人感兴趣。去甲肾上腺素能功能障碍与 AUD、焦虑、慢性应激、抑郁以及情绪和身体疼痛有关。重要的是，去甲肾上腺素能系统中存在关键的性二态性，这些二态性被认为对女性和男性 AUD 的发生和轨迹产生不同的影响。在当前的综述中，我们讨论了过去和最近的工作，即 AUD 周期每个阶段 （暴饮暴食/中毒、戒断/负面影响和关注/预期） 的去甲肾上腺素能影响。这些研究的证据支持优先考虑开发去甲肾上腺素特异性药物治疗 AUD，并确定可能从这些疗法中获益最多的 AUD 亚群（例如，女性或合并慢性疼痛或焦虑/应激障碍的人）。