The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.

IF 4.6 2区医学 Q1 SUBSTANCE ABUSE Current Addiction Reports Pub Date : 2025-01-01 Epub Date: 2025-02-04 DOI:10.1007/s40429-025-00618-x

Renata C N Marchette, Leandro F Vendruscolo, George F Koob

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Abstract

Purpose of review: Drug addiction is characterized by compulsive drug seeking and use, accompanied by negative emotional states (hyperkatifeia) and heightened pain sensitivity (hyperalgesia) during withdrawal. Both hyperalgesia and hyperkatifeia are integral components of substance use disorders, negatively impacting treatment and recovery. The underlying neurobiological mechanisms of hyperalgesia and hyperkatifeia involve alterations of brain reward and stress circuits, including the dynorphin/κ-opioid receptor (KOR) system. The dynorphin/KOR system modulates pain perception, negative affect, and addictive behaviors. Here, we review the preclinical evidence of dynorphin/KOR signaling in opioid withdrawal-induced hyperalgesia and hyperkatifeia.

Recent findings: In opioid dependence models, pharmacological and genetic interventions of the dynorphin/KOR system attenuate somatic and motivational signs of withdrawal and addictive-like behaviors, highlighting its therapeutic potential. Understanding the intricate interplay between dynorphin/KOR signaling, hyperalgesia, hyperkatifeia, and addiction offers novel insights into treatment strategies for opioid use disorder and other substance use disorders.

Summary: Further research is needed to elucidate precise mechanisms of the sexual dimorphism of dynorphin/KOR signaling and identify targeted interventions to mitigate hyperalgesia and hyperkatifeia and facilitate recovery from addiction.

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痛觉过敏/过度兴奋与成瘾性交界的啡啡/-阿片受体系统。

回顾目的：药物成瘾的特征是强迫性寻求和使用药物，在戒断期间伴有负面情绪状态（过度兴奋）和疼痛敏感性增高（痛觉过敏）。痛觉过敏和口臭过度都是物质使用障碍的组成部分，对治疗和恢复产生负面影响。痛觉过敏和过度兴奋的潜在神经生物学机制涉及大脑奖赏和应激回路的改变，包括运动啡/κ-阿片受体（KOR）系统。dynorphin/KOR系统调节痛觉、负面影响和成瘾行为。在这里，我们回顾了阿片类药物戒断引起的痛觉过敏和充血亢进中dynorphin/KOR信号的临床前证据。最近的研究发现：在阿片类药物依赖模型中，dynorphin/KOR系统的药理学和遗传干预可以减弱戒断和成瘾样行为的躯体和动机信号，突出其治疗潜力。了解dynorphin/KOR信号、痛觉过敏、过度兴奋和成瘾之间复杂的相互作用，为阿片类药物使用障碍和其他物质使用障碍的治疗策略提供了新的见解。摘要：需要进一步的研究来阐明dynorphin/KOR信号两性二态性的确切机制，并确定有针对性的干预措施来减轻痛觉过敏和过度兴奋，并促进成瘾的恢复。

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来源期刊

Current Addiction Reports Psychology-Clinical Psychology

CiteScore

6.60

自引率

4.70%

发文量

期刊介绍： This journal focuses on the prevention, assessment and diagnosis, and treatment of addiction. Designed for physicians and other mental health professionals who need to keep up-to-date with the latest research, Current Addiction Reports offers expert reviews on the most recent and important research in addiction. We accomplish this by appointing leaders in the field to serve as Section Editors in key subject areas and disciplines, such asAlcoholTobaccoStimulants, cannabis, and club drugsBehavioral addictionsGender disparities in addictionComorbid psychiatric disorders and addictionSubstance abuse disorders and HIVSection Editors, in turn, select the most pressing topics as well as experts to evaluate the latest research, report on any controversial discoveries or hypotheses of interest, and ultimately bring readers up-to-date on the topic. Articles represent interdisciplinary endeavors with research from fields such as psychiatry, psychology, pharmacology, epidemiology, and neuroscience.Additionally, an international Editorial Board—representing a range of disciplines within addiction medicine—ensures that the journal content includes current, emerging research and suggests articles of special interest to their country or region.