Key Points
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Pathophysiological pain such as inflammatory, neuropathic and cancer pain is characterized by increased pain sensitivity
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Despite a number of approved analgesics, pain therapy is often unsatisfactory because of low efficacy and adverse effects
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Pathophysiological pain is associated with a number of different types of epigenetic modulation
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Future therapeutic interventions in patients who experience pain might target tissue-specific and cell-specific epigenetic mechanisms with histone deacetylase inhibitors, DNA methyltransferase inhibitors, and microRNA mimics or inhibitors
Abstract
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain. Several studies, mostly in animals, revealed that inhibitors of DNA methylation, activators and inhibitors of histone modification and modulators of miRNAs reverse a number of pathological changes in the pain epigenome, which are associated with altered expression of pain-relevant genes. This epigenetic modulation might then reduce the nociceptive response and provide novel therapeutic options for analgesic therapy of chronic pain states. However, a number of challenges, such as nonspecific effects and poor delivery to target cells and tissues, hinder the rapid development of such analgesics. In this Review, we critically summarize data on epigenetics and pain, focusing on challenges in clinical development as well as possible new approaches to the drug modulation of the pain epigenome.
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Acknowledgements
The work of the authors is supported by the Deutsche Forschungsgemeinschaft (SFB1039, Z01), and the LOEWE (Landes-Offensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz (State Initiative for the Development of Scientific and Economic Excellence)) Center for Translational Medicine and Pharmacology.
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All authors, wrote, edited and discussed content for the article. E.N. and E.R carried out the literature search.
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M.J.P. has been a consultant for Leo Pharma and Xellia Pharmaceuticals and was previously an employee of GlaxoSmithKline. G.G. is a member of the IMI (Innovative Medicine Initiative of the European Union) EuroPain collaboration, in which the following industry members are represented: Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Esteve, Grünenthal, Pfizer, UCB Pharma and Sanofi Aventis. In addition, G.G. has received honoraria as a speaker from Grünenthal, Mundipharma and Pfizer. He is a consultant for Abbvie and has received research funding in the form of a grant from Mundipharma.
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Niederberger, E., Resch, E., Parnham, M. et al. Drugging the pain epigenome. Nat Rev Neurol 13, 434–447 (2017). https://doi.org/10.1038/nrneurol.2017.68
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DOI: https://doi.org/10.1038/nrneurol.2017.68
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