Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders

Curr Opin Neurobiol. 2018 Feb;48:37-44. doi: 10.1016/j.conb.2017.09.006. Epub 2017 Sep 28.


Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anxiety Disorders* / genetics
  • Anxiety Disorders* / pathology
  • Anxiety Disorders* / physiopathology
  • Avoidance Learning / physiology*
  • Conditioning, Classical
  • Endophenotypes*
  • Fear
  • Humans
  • Memory
  • Pain* / genetics
  • Pain* / pathology
  • Pain* / physiopathology
  • Signal Transduction / physiology*