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

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.