Central amygdala activation of extracellular signal-regulated kinase 1 and age-dependent changes in inflammatory pain sensitivity in mice

Neurobiol Aging. 2017 Aug;56:100-107. doi: 10.1016/j.neurobiolaging.2017.04.010. Epub 2017 Apr 26.


Aging populations are more sensitive to noxious stimuli as a result of altered somatosensory systems. In these experiments, we examined pain-like behaviors in young, middle-aged, and old mice during peripheral inflammation to determine if the same sensitivity exists in preclinical animal models. Immediately following injury, middle-aged and old mice exhibited more spontaneous pain-like behaviors than young mice, matching pain prevalence in clinical populations. Middle-aged and old mice also developed persistent mechanical hypersensitivity in the injured paw. Furthermore, old mice developed mechanical hypersensitivity in the noninjured paw suggesting age-dependent changes in central nociceptive systems. To address this end, pain-related protein expression was examined in the central nucleus of the amygdala, a limbic brain region that modulates somatic pain. Following injury, increased phosphorylation of extracellular signal-regulated kinase 1, a protein with known nociceptive functions, was observed in the right central nucleus of the amygdala of old mice and not middle-aged or young animals. These findings suggest that age-dependent changes in supraspinal nociceptive systems may account for increased pain-like behaviors in aging populations.

Keywords: Amygdala; ERK1/2; Pain; mGluR5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / physiology*
  • Animals
  • Central Amygdaloid Nucleus / enzymology*
  • Disease Models, Animal
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nociception / physiology*
  • Pain*
  • Phosphorylation
  • Physical Stimulation
  • Receptor, Metabotropic Glutamate 5 / metabolism
  • Somatosensory Cortex / physiopathology


  • Grm5 protein, mouse
  • Receptor, Metabotropic Glutamate 5
  • Mitogen-Activated Protein Kinase 3