Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Department of Pharmacology, University of California Irvine Irvine, CA, USA ; Department of Biomedical and Molecular Sciences, Queen's University Kingston, ON, Canada.
Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles Los Angeles, CA, USA.
Front Pharmacol. 2014 Nov 17;5:253. doi: 10.3389/fphar.2014.00253. eCollection 2014.
The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.
κ 阿片受体（KOR）和内源性肽配体强啡肽由于参与介导多种行为和神经生理反应而受到广泛关注，包括对抗包括阿片类药物在内的滥用药物的奖赏特性。越来越多的证据表明，该系统参与调节动机和情绪状态。KOR 的急性激活会增加逃避威胁的动机行为，然而，与慢性应激相关的 KOR 激活会导致情绪障碍症状的表达。人们普遍认为 KOR 可以产生镇痛作用，并参与包括神经性疼痛在内的慢性疼痛状态。脊髓研究表明，KOR 诱导的镇痛作用可以逆转与周围神经损伤相关的痛觉过敏。虽然 KOR 激动剂的全身给药可以减弱伤害性感觉传递，但这种作用似乎是一种应激诱导的效应，因为阿片受体 δ 激动剂可以减轻 KOR 激动剂诱导的镇痛作用。此外，虽然 KOR 和强啡肽在驱动应激和药物戒断的不愉快和厌恶成分方面的作用已经得到很好的描述，但该系统如何介导与慢性疼痛相关的负面情绪状态相对来说还没有被探索。这篇综述提供了证据表明，强啡肽和 KOR 系统有助于疼痛的负面情感成分，并且该受体系统可能与慢性神经性疼痛相关的情绪障碍的高共病性有关。
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