Amygdala pain mechanisms

Handb Exp Pharmacol. 2015:227:261-84. doi: 10.1007/978-3-662-46450-2_13.


A limbic brain area, the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety, and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the "nociceptive amygdala") accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Calcitonin / physiology
  • Corticotropin-Releasing Hormone / physiology
  • Humans
  • Neuronal Plasticity / physiology
  • Neuropeptides / physiology
  • Pain / physiopathology*
  • Protein Precursors / physiology
  • Receptor, Metabotropic Glutamate 5 / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • gamma-Aminobutyric Acid / physiology


  • Neuropeptides
  • Protein Precursors
  • Receptor, Metabotropic Glutamate 5
  • Receptors, N-Methyl-D-Aspartate
  • neuropeptide S, human
  • gamma-Aminobutyric Acid
  • Calcitonin
  • Corticotropin-Releasing Hormone