Possible Reversal of PTSD-Related DNA Methylation by Sympathetic Blockade

J Mol Neurosci. 2017 May;62(1):67-72. doi: 10.1007/s12031-017-0911-3. Epub 2017 Mar 31.


Studies have shown that brain-derived neurotrophic factor (BDNF) level increase is associated with post-traumatic stress disorder (PTSD) risk. BDNF may be a "missing-link" that mediates the interaction between genetics, environment, and the sympathetic system. Trauma has been shown to induce DNA methylation that in turn can increase BDNF concentration due to increased gene expression. Therapies that focus on the reduction of beta-NGF (BNGF) levels may impact PTSD symptoms. The focus of this paper is to discuss possible effect of stellate ganglion block (SGB) on epigenetic changes noted with PTSD mediated by BDNF and NGF. Stellate ganglion block has recently shown significant therapeutic efficacy for treatment of PTSD symptoms. Previously reported theoretical mechanisms of SGB impact on PTSD have focused on likely reduction of NGF, leading to eventual loss of extraneous sympathetic nerve growth, eventually leading to reduction of secondary norepinephrine level, which in turn is hypothesized to reduce PTSD symptoms. We used PUBMED to obtain available data following a search for the following: DNA, neurotrophic factors, post-traumatic stress disorder, and demethylation following local anesthetic application. A number of articles meeting criteria were found and reviewed. Based on the evidence summarized, trauma can lead to DNA methylation, as well as BNGF/NGF level increase, which in turn starts a cascade of sympathetic sprouting, leading to increased brain norepinephrine, and finally symptomatic PTSD. Cascade reversal may occur in part by demethylation of DNA caused by application of local anesthetic to the stellate ganglion.

Keywords: Anxiety; Autonomic dysfunction; BNGF; Brain-derived neurotrophic factor; Cervical sympathetic chain; DNA methylation; NGF; Nerve growth factor; PTSD; Post-traumatic stress disorder; SGB; Stellate ganglion block.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • DNA Methylation*
  • Ganglionic Blockers / pharmacology*
  • Humans
  • Norepinephrine / metabolism
  • Stellate Ganglion / drug effects*
  • Stellate Ganglion / metabolism
  • Stellate Ganglion / physiology
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / physiopathology


  • Brain-Derived Neurotrophic Factor
  • Ganglionic Blockers
  • Norepinephrine