Department of Clinical and Experimental Medicine, Unit of Psychiatry, Azienda Ospedaliero Universitaria Pisana AUOP, Pisa, Italy.
Département de Psychiatrie et D'Addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, Paris, France.
J Sleep Res. 2023 Aug;32(4):e13825. doi: 10.1111/jsr.13825. Epub 2023 Feb 14.
Insomnia disorder is considered as a stress-related disorder associated with hyperarousal, stress and emotion dysregulation and the instability of the 'flip-flop' switch system. The orexinergic system is well known for its key role in sleep and arousal processes but also in the allostatic system regulating stress and emotions and may thus be of major interest for insomnia and its treatment. Accordingly, we discuss the potential role of orexins on sleep processes, brain systems modulating stress and emotions with potential implications for insomnia pathophysiology. We reviewed available data on the effect of dual orexin receptor antagonists (DORAs) on sleep and brain systems modulating stress/emotions with implications for insomnia treatment. We present our findings as a narrative review. Few data in animals and humans have reported that disrupted sleep and insomnia may be related to the overactivation of orexinergic system, while some more consistent data in humans and animals reported the overactivation of orexins in response to acute stress and in stress-related disorders. Taken together these findings may let us hypothesise that an orexins overactivation may be associated with stress-related hyperarousal and the hyperactivation of arousal-promoting systems in insomnia. On the other hand, it is possible that by rebalancing orexins with DORAs we may regulate both sleep and allostatic systems, in turn, contributing to a 'switch off' of hyperarousal in insomnia. Nevertheless, more studies are needed to clarify the role of the orexin system in insomnia and to evaluate the effects of DORAs on sleep, stress and emotions regulating systems.
失眠障碍被认为是一种与过度觉醒、应激和情绪调节障碍以及“翻转开关”系统不稳定相关的应激相关障碍。食欲肽系统在睡眠和觉醒过程中起着关键作用，在调节应激和情绪的适应系统中也起着重要作用，因此，它可能是失眠及其治疗的主要关注点。相应地，我们讨论了食欲肽对睡眠过程、调节应激和情绪的脑系统的潜在作用及其对失眠病理生理学的潜在影响。我们回顾了关于双重食欲肽受体拮抗剂（DORAs）对睡眠和调节应激/情绪的脑系统的影响的现有数据，这些数据对失眠治疗具有重要意义。我们以叙述性综述的形式呈现我们的发现。动物和人类的一些数据表明，睡眠中断和失眠可能与食欲肽系统的过度激活有关，而一些在人类和动物中更一致的数据则表明，食欲肽在急性应激和应激相关障碍中过度激活。这些发现表明，食欲肽的过度激活可能与应激相关的过度觉醒和失眠中觉醒促进系统的过度激活有关。另一方面，通过用 DORAs 来重新平衡食欲肽，我们可能会调节睡眠和适应系统，从而有助于失眠中的过度觉醒“关闭”。然而，还需要更多的研究来阐明食欲肽系统在失眠中的作用，并评估 DORAs 对睡眠、应激和情绪调节系统的影响。
