Epigenetics in pain and analgesia: an imminent research field.
Heritable phenotypes resulting from environment-caused changes in a chromosome without alterations in the DNA sequence are increasingly recognized as a basis of personalized therapy. Epigenetic mechanisms include covalent modifications of the DNA (methylation) or of the DNA-packaging histones (e.g., deacetylation or phosphorylation). In addition, regulatory non-coding RNA molecules (micro-RNAs) exert epigenetic actions. This leads to disruption or otherwise modified expression of genes. Environmental influences such as nutritional factors, exposure to chemicals or drugs, but also social factors appear to exert epigenetic actions. Histone modifications and DNA methylation are associated with the subject's age. Epigenetic mechanisms can silence the expression of pro- or antinociceptive genes. To the epigenetic control of nociception adds its control of the pharmacodynamics or pharmacokinetics of analgesics by epigenetic control of drug targets and analgesics metabolizing enzymes. Although epigenetics-based strategies for pain therapy are not yet available, experiments in rodents suggest that RNA interference may become a new therapy approach for neuropathic and other pain. Another epigenetic approach to analgesic treatment employs inhibitors of histone deacetylase that act on the epigenome by indirectly remodeling the spatial conformation of the chromatin. Finally, epigenetic techniques such as RNA interference have been employed in pain research to proof the contribution of certain proteins to nociception. Thus, the new field of epigenetics becomes increasingly used in research and management of pain and will complement genetics. This article introduces epigenetics to pain and summarizes the current and future utility.
Doehring
Alexandra
A
pharmazentrum frankfurt/ZAFES, Institute for Clinical Pharmacology, Goethe-University, Theodor Stern Kai 7, Frankfurt am Main, Germany.
Geisslinger
Gerd
G
Lötsch
Jörn
J
D000698:Analgesia; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D057890:Epigenomics; D004843:Epistasis, Genetic / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D010146:Pain / Q000235:genetics*; D059408:Pain Management; D017288:Pain Threshold; D034622:RNA Interference / Q000502:physiology; D012307:Risk Factors
D002843:Chromatin; D006657:Histones; D006655:Histone Deacetylases