Epigenetics and the transition from acute to chronic pain.
Epigenetics and the transition from acute to chronic pain.
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DOI：
10.1111/j.1526-4637.2012.01488.x
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Shaw A
中科院分区：
文献类型：
--
作者：
Buchheit T;Van de Ven T;Shaw A
回顾从急性疼痛过渡到慢性疼痛的表观遗传修饰，并确定开发新型、个性化疼痛治疗的潜在靶点。表观遗传学是研究基因表达和表型的可遗传修饰，这些修饰不需要改变基因序列就能显示其作用。环境毒素、药物、饮食和心理压力可以改变表观遗传过程，如DNA甲基化、组蛋白乙酰化和RNA干扰。由于表观遗传修饰可能在炎症细胞因子代谢、类固醇反应性和阿片类药物敏感性中发挥重要作用，因此它们可能是慢性疼痛发展的关键因素。尽管我们对人类遗传密码和疾病相关多态性的了解在过去十年中有了显著增长，但我们尚未能够阐明导致神经损伤或手术后持续疼痛发展的机制。重要的实验室和临床数据支持表观遗传修饰受环境影响并导致差异基因表达的观点。与癌症、神经退行性疾病和炎症性疾病的发生机制类似，文献支持表观遗传学在慢性疼痛中的重要潜在作用。表观遗传学分析可以确定损伤后慢性疼痛发展的关键机制，并可能为未来的药物开发和个体化治疗提供新的途径和靶点机制。
To review the epigenetic modifications involved in the transition from acute to chronic pain and to identify potential targets for the development of novel, individualized pain therapeutics. Epigenetics is the study of heritable modifications in gene expression and phenotype that do not require a change in genetic sequence to manifest their effects. Environmental toxins, medications, diet, and psychological stresses can alter epigenetic processes such as DNA methylation, histone acetylation, and RNA interference. Since epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, steroid responsiveness, and opioid sensitivity, they are likely key factors in the development of chronic pain. Although our knowledge of the human genetic code and disease-associated polymorphisms has grown significantly in the past decade, we have not yet been able to elucidate the mechanisms that lead to the development of persistent pain after nerve injury or surgery. Focused literature review Significant laboratory and clinical data support the notion that epigenetic modifications are affected by the environment and lead to differential gene expression. Similar to mechanisms involved in the development of cancer, neurodegenerative disease, and inflammatory disorders, the literature endorses an important potential role for epigenetics in chronic pain. Epigenetic analysis may identify mechanisms critical to the development of chronic pain after injury, and may provide new pathways and target mechanisms for future drug development and individualized medicine.
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