Epigenetic regulation in opioid induced hyperalgesia.
Epigenetic regulation in opioid induced hyperalgesia.
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DOI：
10.1016/j.ynpai.2023.100146
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发表时间：
2023-08
期刊：
影响因子：
--
通讯作者：
Ajit, Seena K.
中科院分区：
文献类型：
--
作者：
Reddy, Deepa;Wickman, Jason R.;Ajit, Seena K.
阿片类药物使用和OIH引起的表观遗传变化尚未得到充分研究。一些随着阿片类药物使用和疼痛而改变的miRNAs可以调节μ阿片受体。关于表观遗传调节剂如何促进OIH的知识存在空白。阐明表观遗传机制可以揭示OIH的新治疗策略。大约有2500万美国成年人每天都会经历疼痛，治疗疼痛的最常用药物之一是阿片类药物。阿片类药物的长期使用和剂量增加可能会导致矛盾的反应，患者的疼痛敏感性增强。阿片类药物引起的痛觉过敏（OIH）是临床治疗疼痛的主要障碍，因为其潜在机制尚未完全了解。OIH也经常被忽视，缺乏预防其发作的指导方针。对疼痛障碍和阿片类药物使用的研究已经认识到疾病的潜在表观遗传驱动因素，包括DNA甲基化，组蛋白修饰，miRNA调控，但它们在OIH中的参与尚未得到充分研究。本文讨论了可能导致发病机制的表观遗传学变化，重点是OIH中的miRNA改变。在知识上存在着一个关键的空白，包括多种表观遗传调节剂如何促成OIH。阐明OIH潜在的表观遗传变化和这些机制之间的串扰可能会导致开发新的靶点来预防和治疗这种疼痛现象。
Epigenetic changes resulting from opioid use and OIH are not well studied. Some miRNAs altered with opioid use and pain can regulate mu opioid receptor. There is a gap in knowledge on how epigenetic modulators contribute to OIH. Elucidating epigenetic mechanisms can unravel novel therapeutic strategies for OIH. About 25 million American adults experience pain daily and one of the most commonly prescribed drugs to treat pain are opioids. Prolonged opioid usage and dose escalations can cause a paradoxical response where patients experience enhanced pain sensitivity. This opioid induced hyperalgesia (OIH) is a major hurdle when treating pain in the clinic because its underlying mechanisms are still not fully understood. OIH is also commonly overlooked and lacks guidelines to prevent its onset. Research on pain disorders and opioid usage have recognized potential epigenetic drivers of disease including DNA methylation, histone modifications, miRNA regulation, but their involvement in OIH has not been well studied. This article discusses epigenetic changes that may contribute to pathogenesis, with an emphasis on miRNA alterations in OIH. There is a crucial gap in knowledge including how multiple epigenetic modulators contribute to OIH. Elucidating the epigenetic changes underlying OIH and the crosstalk among these mechanisms could lead to the development of novel targets for the prevention and treatment of this painful phenomena.
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