For decades the broad role of opioids in addiction, neuropsychiatric disorders, and pain states has been somewhat well established. However, in recent years, with the rise of technological advances, not only is the existing dogma being challenged, but we are identifying new disease areas in which opioids play a critical role. This review highlights four new areas of exploration in the opioid field. The most recent addition to the opioid family, the nociceptin receptor system, shows promise as the missing link in understanding the neurocircuitry of motivation. It is well known that activation of the kappa opioid receptor system modulates negative affect and dysphoria, but recent studies now implicate the kappa opioid system in the modulation of negative affect associated with pain. Opioids are critical in pain management; however, the often-forgotten delta opioid receptor system has been identified as a novel therapeutic target for headache disorders and migraine. Lastly, changes to the gut microbiome have been shown to directly contribute to many of the symptoms of chronic opioid use and opioid related behaviors. This review summarizes the findings from each of these areas with an emphasis on identifying new therapeutic targets.

中文翻译：

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疼痛、动机、偏头痛和微生物组：阿片类药物系统和疾病的新前沿。

几十年来，阿片类药物在成瘾、神经精神疾病和疼痛状态中的广泛作用已经在某种程度上得到了很好的证实。然而，近年来，随着技术进步的兴起，不仅现有的教条受到挑战，而且我们正在确定阿片类药物在其中发挥关键作用的新疾病领域。本综述重点介绍了阿片类药物领域的四个新探索领域。阿片类药物家族的最新成员，伤害感受素受体系统，显示出作为理解动机神经回路的缺失环节的希望。众所周知，κ阿片受体系统的激活会调节负面情绪和烦躁不安，但最近的研究表明，κ阿片类物质系统参与了与疼痛相关的负面情绪的调节。阿片类药物在疼痛管理中至关重要；然而，经常被遗忘的 delta 阿片受体系统已被确定为头痛疾病和偏头痛的新治疗靶点。最后，肠道微生物组的变化已被证明直接导致慢性阿片类药物使用和阿片类药物相关行为的许多症状。本综述总结了每个领域的发现，重点是确定新的治疗靶点。