Posted on Oct 15, 2018, 1 a.m.
Prolonged exposure of the central amygdala to elevated corticosteroids facilitates long term anxiety and pain through activation of glucocorticoid receptors and corticotropin releasing factors, but the underpinning mechanisms maintaining the responses are not known.
Chronic phenotypes can be sustained by epigenetic mechanisms including histone modifications such as deacetylation. In this study which is published in Nature: Molecular Psychiatry researchers set out to test the hypothesis of histone deacetylation contributing to maintenance of chronic anxiety and pain induced by prolonged exposure of the central amygdala to elevated corticosteroids.
Researchers found that bilateral infusions of a histone deacetylase inhibitor into the central amygdala attenuated anxiety like behavior along with somatic and visceral hypersensitivity resulting from elevated corticosteroid exposure. Researchers were able to delineate a novel pathway through which histone deacetylation could contribute to corticosteroid regulation of glucocorticoid receptors and subsequent corticotropin releasing factor expression in the central amygdala, specifically through deacetylation of histone 3 at lysine 9 via coordinated action of the NAD+ dependent protein deacetylase sirtuin-6 and nuclear factor kappa B sequester GR expression leading to disinhibition of corticotropin releasing factor.
According to the researchers their results suggest that epigenetic programming within the amygdala are important in the maintenance of chronic pain and anxiety, specifically histone modification. If this is generalizable to human mechanisms of chronic anxiety and pain maintenance it would provide a method of preventing and treating chronic pain and anxiety.