Nature medicine
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The formation of blood clots--thrombosis--at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has led to the development of newer therapeutics, and there is general anticipation that these treatments will have greater efficacy and improved safety. However, major advances in this field require the identification of specific risk factors for arterial thrombosis in affected individuals and a rethink of the 'one size fits all' approach to antithrombotic therapy.
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Chronic pain is a common neurological disease involving lasting, multifaceted maladaptations ranging from gene modulation to synaptic dysfunction and emotional disorders. Sustained pathological stimuli in many diseases alter the output activities of certain genes through epigenetic modifications, but it is unclear how epigenetic mechanisms operate in the development of chronic pain. ⋯ In wild-type but not Gad2 knockout mice, HDAC inhibitors strongly increased GAD65 activity, restored GABA synaptic function and relieved sensitized pain behavior. These findings suggest GAD65 and HDACs as potential therapeutic targets in an epigenetic approach to the treatment of chronic pain.